The in situ generation of alk-1-ynyllead triacetatesfrom terminal acetylenes by zincndash;lead exchange and crystalstructure of2,4,7,9,13-pentamethyl-9-phenylethynyl-7,10-ethenospiro5.5undeca-1,4-diene-3,8-dione

摘要

J. Chem. Soc. Perkin Trans. 1 1997 1465 The in situ generation of alk-1-ynyllead triacetates from terminal acetylenes by zincndash;lead exchange and crystal structure of 2,4,7,9,13- pentamethyl-9-phenylethynyl-7,10-ethenospiro5.5undeca-1,4-diene- 3,8-dione Christopher J. Parkinson Trevor W. Hambley and John T. Pinhey * School of Chemistry University of Sydney Sydney 2006 Australia Methods involving zincndash;lead exchange for the one-pot conversion of terminal acetylenes into alk-1- ynyllead(IV) triacetates have been developed and examples of the in situ C-alkynylation of a number of carbon nucleophiles are reported. An attempt to extend the reaction to phenols by treating 2,4,6- trimethylphenol with phenylethynyllead triacetate led to formation of the spiro dienone 16 the structure of which was determined by X-ray diffraction.In an earlier paper we reported a new general method for the Calkynylation of soft carbon nucleophiles such as b-dicarbonyl compounds and sodium nitronates.1 The procedure involved the treatment of the nucleophile with an alk-1-ynyllead triacetate unstable compounds which may be produced in solution by the reaction of either an alk-1-ynyl(trimethyl)stannane or a di(alk-1-ynyl)mercury compound with lead tetraacetate (LTA) (Scheme 1). The development of a one-pot procedure for converting an acetylene into an alkynyllead triacetate in situ was recognised by us as a potentially useful extension of the method especially because of the moisture sensitivity of alk-1-ynyl(trimethyl)- stannanes. Such a method was later reported by Ikegami,2 who found that if a tetrahydrofuran solution of a lithium acetylide was added at low temperature to LTA in methylene dichloride the resulting mixture reacted at room temperature with a range of b-keto benzyl esters to give good yields of the corresponding a-alkynylated keto esters.We have attempted to use this procedure to produce the a-hex-1-ynyl b-keto ester 11; however we found that reaction of ethyl 2-oxocyclopentanecarboxylate 1 under the conditions reported resulted in formation of the dimer 2 in approximately 72 yield and recovery of about 9 of the keto ester 1 (see Scheme 2). None of the hexynyl derivative 11 could be detected in the reaction mixture. Compound 2 is readily formed by treatment of the b-keto ester 1 with LTA,3 which would indicate that the relatively fast disproportionation of the alkynyllead triacetate to the tetraalkynyllead and LTA Scheme 1 Scheme 2 Reagents and conditions i Mixture from reaction of C4H9C CLi and Pb(OAc)4 at 220 8C then 15 min at RT; ii Pb(OAc)4 which we had noted previously,1 had occurred eqn.(1). This would suggest that in the case of the b-keto ethyl ester 1 alkynylation is slower than for the corresponding benzyl ester. In previous work it has been noted by ourselves 4 and by Ikegami and co-workers 5 that the reactivity of b-keto esters towards organolead triacetates is dependent on the nature of the ester group; methyl esters and benzyl esters were found to be more reactive than ethyl esters. At about the same time as the communication of Ikegami we had found that alkynylzinc chlorides reacted with LTA to give a solution which had the capacity to carry out the electrophilic alkynylation of b-keto esters.This reaction which has been developed into a useful one-pot method for the C-alkynylation of soft carbon nucleophiles is outlined for the synthesis of the keto ester 3 (see Scheme 3). The most efficient and readily reproduced procedure which afforded a 73 yield of the phenylethynyl derivative 3 involved the treatment of phenylacetylene (1.2 mol equiv.) in tetrahydrofuran with butyllithium at 278 8C. Zinc chloride (1.2 mol equiv.) was added to the solution which was then stirred at 210 8C for 20 min. A solution of LTA (1.1 mol equiv.) in chloroform was then added at 210 8C to the solution which was then stirred for 15 s. After this the substrate 1 (1.0 mol equiv.) in chloroform was added to the mixture which was then stirred at 210 8C for 1 h and a further 2 h at room temperature.As we found previously in the case of Snndash;Pb and Hgndash;Pb exchange reactions,1 the time allowed for Znndash;Pb exchange is most important for the success of the reaction. This as indicated above is due to disproportionation of the alkynyllead triacetate which is outlined in eqn. (1). As can be seen from Table 1 the optimum yield of compound 3 was obtained after a Znndash;Pb exchange time of 15 s; any increase in this time resulted in formation of more of the dimer 4 and with a delay of 15 min Scheme 3 Reagents and conditions i BuLi THF 278 8C; ii ZnCl2; iii LTA CHCl3 210 8C then RT 0.25 min; iv compound 1 1466 J. Chem. Soc. Perkin Trans. 1 1997 before addition of the substrate 1 the product contained 33 of compound 4.The formation of the dimer 4 in the above reaction (Scheme 3) is noteworthy since the CO linked dimer 2 is the product of LTA oxidation of the keto ester 1.3 It appeared likely that the presence of zinc chloride caused the change in the mode of oxidative dimerisation and this was examined by treating the keto ester 1 with LTA (0.5 mol equiv.) and zinc chloride in chloroform. The CC linked dimer 4 was produced in 67 yield as a single diastereoisomer suggesting that the product arises in a radical coupling of two molecules complexed to a zinc ion through oxygen. In exploring the generality of the above one-pot alkynylation method the b-diketone 5 and the sodium nitronate 6 were found to react readily under the conditions indicated in Scheme 3 to give the phenylethynyl derivatives 7 and 9 in yields of 59 and 58 respectively.An initial attempt to extend the method by replacing phenylacetylene with oct-1-yne in Scheme 3 resulted in production of some of the expected keto ester 12; however there was significant dimer 4 formation. This problem was readily overcome by introducing a catalytic amount of mercury(II) acetate (0.1 mol equiv.) with the LTA and maintaining all other conditions as in Scheme 3. The modified method resulted in a 52 yield of the keto ester 12 and it would appear to be potentially useful for the introduction of a variety of alkynyl groups since the nucleophiles 5 and 6 behaved similarly to the b-keto ester 1 affording the octynyl derivatives 8 (52) and 10 (41) respectively in synthetically useful yields. Although yields in five of the six alkynylations were below those which we reported for alkynyllead triacetates generated for alkynyl(trimethyl)stannanes,1 the method offers greater effi- ciency in the use of the acetylene and its simplicity is a considerable advantage.The need to employ a catalytic amount of mercury(II) acetate for the octynylation reactions requires some comment. We had found in previous work6 that arylboronic acids react with LTA to give diaryllead diacetates whereas the same reaction conducted with a catalytic amount of mercury(II) acetate produced the aryllead triacetate in high yield. Thus we reasoned that the octynylzinc reagent may be reacting in a similar way with LTA to yield octynyllead triacetate and dioctynyllead diacetate but only the former lead compound with LTAndash;Hg(OAc)2.Thus in the absence of Hg(OAc)2 unchanged LTA would be available to produce the dimer 4. An attempt to extend the method to include the alkynylation of phenols was not successful and we attribute this to their lower reactivity towards organolead triacetates as found by us in earlier work.7ndash;9 When 2,4,6-trimethylphenol (mesitol) 13 was added to the mixture produced by use of the above conditions for Znndash;Pb exchange with phenylacetylene none of the 6- phenylethynyl dienone 14 (or its dimer) 8 was detected. The product of Wessely acetoxylation compound 15 was present in 11 yield (see Scheme 4); however the major product of the reaction was the novel spirodienone 16 the structure of which was determined by X-ray diffraction (see below). The pathway to compound 16 no doubt involves a Dielsndash;Alder condensation between the 6-phenylethynylcyclohexadienone 14 and the mesitol oxidation product 17 (see Scheme 5).This latter compound could arise by elimination of HX from either the 6-acetoxy- Table 1 Effect of Znndash;Pb exchange time on the ratio of the acetylene derivative 3 to dimer 4 in the reaction of Scheme 3 conducted at 210 8C Znndash;Pb exchange time (min) Molar ratio of (3) (4) Total yield () 0.25 0.5 2.0 15.0 9.5 1 8.1 1 4.3 1 2 1 88 83 75 78 cyclohexadienone 15 or the corresponding chloride as shown. The fact that compound 16 is obtained as a single diastereoisomer is readily explicable in terms of the least hindered approach of the dienophile in the condensation. A single-crystal X-ray analysis (see Experimental section) of the spiro compound 16 showed that the structure consists of neutral molecules packed with no contacts shorter than those expected on the basis of the van der Waals radii as shown in Fig.1. There is a triple bond between C(19) and C(20) and double bonds between C(4) and C(5) C(9) and C(10) C(12) and C(13) C(2) and O(1) and between C(11) and O(2). The phenylacetylene and cyclohexa-2,5-dienone moieties are both planar to within 0.05 Aring;. Long bonds between C(3) and C(8) 1.61(1) Aring; and between C(7) and C(8) 1.57(1) Aring; reflect the strain about the quaternary atom C(8). Experimental Mps were determined on a Kofler hot-stage and are uncorrected. Column chromatography was carried out on Merck Kieselgel 60 (230ndash;240 mesh). IR spectra were recorded on a Digilab FTS-80 spectrometer and NMR spectra were deter- Scheme 4 Reagents and conditions i BuLi THF 278 8C; ii ZnCl2; iii LTA CHCl3 210 8C then RT 0.25 min; iv compound 13 Scheme 5 J.Chem. Soc. Perkin Trans. 1 1997 1467 mined with SiMe4 as internal standard on Bruker AMX-400 and AC-200B spectrometers. J Values are given in Hz. Microanalyses were performed by the microanalytical unit of the School of Chemistry University of New South Wales and mass spectra were recorded on an AEI model MS902 double focusing instrument. General method for the reaction of carbon nucleophiles with phenylethynyllead triacetate generated in situ by Znndash;Pb exchange Phenylacetylene (0.51 g 5.0 mmol) was dissolved in dry tetrahydrofuran (5 cm3). Butyllithium solution (2.0 M; 2.5 cm3 5.0 mmol) in hexane was added at 278 8C to the mixture which was then stirred for 20 min under nitrogen.Zinc chloride (0.68 g 5.0 mmol) was added to the mixture after which it was allowed to warm to 210 8C; after being stirred at 210 8C for 30 min the mixture was diluted with chloroform (20 cm3) at 210 8C. Lead tetraacetate (2.03 g 4.58 mol) in chloroform (20 cm3) was added to the mixture after which it was stirred at 210 8C for 15 s. The substrate (4.17 mmol) in chloroform (4 cm3) (for 1 and 5) or THF (8 cm3) (for 6) was added to the solution which was then stirred at 2108 for 1 h followed by 2 h at room temperature. The mixture was then poured into diethyl ether (200 cm3) filtered through Celite and evaporated to give the crude product. The following compounds were synthesised by the above method. (i) Ethyl 2-oxo-1-(phenylethynyl)cyclopentanecarboxylate 3 (0.78 g 73).Separated by HPLC (Whatman Partisil 10 M20) in ethyl acetatendash;light petroleum (1 49) as a colourless oil. It had 1H NMR and IR spectroscopic data in accord with literature values.1 (ii) 2-Acetyl-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)- one 7. Separated as an oil (0.71 g 59) by flash chromatography in ethyl acetatendash;light petroleum (1 19). The 1H NMR and IR spectra were identical with those obtained previously.1 (iii) 3-Methyl-3-nitro-1-phenylbut-1-yne 9. Obtained as an oil (0.46 g 58) by flash chromatography in ethyl acetatendash;light petroleum (1 19). The 1H NMR and IR spectra correspond with those obtained previously.1 General method for the reaction of carbon nucleophiles with oct- 1-ynyllead triacetate in situ by Znndash;Pb exchange Oct-1-yne (0.55 g 5.0 mmol) was dissolved in dry tetrahydrofuran (5 cm3).A solution of butyllithium (2.2 M; 2.25 ml 5.0 mmol) in hexane was added at 278 8C to the mixture which was then stirred for 20 min under nitrogen. Zinc chloride (0.68 g 5.0 mmol) was added to the solution after which it was Fig. 1 X-Ray molecular structure of spirocyclohexa-2,5-dienone 16 (with atomic numbering used in the crystallographic data) allowed to warm to 210 8C at which temperature it was stirred for 30 min; it was then diluted with chloroform (10 cm3) at 210 8C. Lead tetraacetate (2.03 g 4.58 mmol) and mercuric acetate (0.15 g 0.46 mmol) in chloroform (20 cm3) were added to the solution after which it was stirred at 210 8C for 15 s. The substrate (4.17 mmol) in chloroform (3 cm3) (for 1 and 5) or tetrahydrofuran (8 cm3) (for 6) was added to the solution which was then stirred at 210 8C for 1 h followed by 2 h at room temperature.The mixture was finally poured into diethyl ether (200 ml) filtered through Celite and evaporated to give the crude product. The following compounds were obtained by the above method. (i) Ethyl 1-(oct-1-ynyl)-2-oxocyclopentanecarboxylate 12. Separated by flash chromatography in ethyl acetatendash;light petroleum (7 95) as a colourless oil (0.57 g 52). The 1H NMR and IR specroscopic data were identical with those obtained previously.1 (ii) 2-Acetyl-2-(oct-1-ynyl)-3,4-dihydronaphthalen-1(2H)- one 8. Obtained by flash chromatography in ethyl acetatendash;light petroleum (1 19) as an oil (0.64 g 52). The 1H NMR and IR spectroscopic data were in accord with literature values.1 (iii) 2-Methyl-2-nitrodec-3-yne 10.Separated by flash chromatography in ethyl acetatendash;light petroleum (3 97) as an oil (0.34 g 41). The 1H NMR and IR spectroscopic data were identical with those previously reported.10 Oxidation of ethyl 2-oxocyclopentanecarboxylate 1 by LTA in the presence of ZnCl2 Lead tetraacetate (2.42 g 5.46 mol) in chloroform (10 cm3) was added to a solution of ethyl 2-oxocyclopentanecarboxylate (1.53 g 9.83 mmol) in chloroform (10 cm3) and tetrahydrofuran (10 cm3) at 210 8C and the mixture was stirred at 210 8C for 1 h followed by 2 h at room temperature. The mixture was then poured into diethyl ether (200 cm3) filtered through Celite and evaporated. The crude material was fractionated by flash chromatography (ethyl acetatendash;light petroleum 2 23) to yield the dimer 4 as a colourless oil (1.025 g 67) (Found C 61.7; H 7.4.C16H22O6 requires C 61.9; H 7.1); dH(CDCl3) 4.29 (4 H q J 7.1 2 times; CO2CH2CH3) 2.86ndash;2.72 (2 H dt J 14.1 10.4 3-H and 39-H) 2.71ndash;2.27 (6-H m 3-H 39-H 5-H2 and 59-H2) 2.26ndash; 2.07 (4-H m 4-H2 and 49-H2) and 1.32 (6 H t J 7.1 2 times; CO2CH2CH3); dC(CHCl3) 205.9 (C-2 and C-29) 166.9 (2 times; CO2Et) 69.4 (C-1 and C-19) 62.7 (2 times; CO2CH2CH3) 38.1 (C-3 and C-39) 35.0 (C-5 and C-59) 18.8 (2 times; CH3) and 13.6 (C-4 and C-49); nmax(CHCl3)/cm21 1768 and 1723; m/z 164 (M 2 2 times; CO2Et 13) 162 (26) 145 (13) 135 (25) 134 (18) 132 (14) 123 (13) 122 (26) 120 (20) 117 (28) 109 (66) 108 (34) 107 (76) 99 (32) 89 (28) 82 (41) 81 (26) 73 (20) and 55 (100). Reaction of 2,4,6-trimethylphenol (mesitol) 13 with phenylethynyllead triacetate produced by Znndash;Pb exchange Butyllithium in hexane (2.0 M; 3.5 cm3 7.06 mmol) was added to phenylacetylene (0.72 g 7.06 mmol) in dry THF (7.0 cm3) at 278 8C and the mixture was stirred for 20 min under N2.Zinc chloride (0.96 g 7.06 mmol) was added to the solution which was then allowed to warm to 210 8C at which temperature it was stirred for 30 min. Chloroform (25 cm3) was added to the mixture followed by LTA (2.84 g 6.42 mmol) in chloroform (25 cm3); the mixture was then stirred at 210 8C for 15 s. Mesitol 13 (0.80 g 5.88 mmol) in chloroform (6 cm3) and pyridine (1.01 g 12.8 mol) were then added to the mixture after which it was stirred at 210 8C for 1 h followed by 3 h at room temperature. After this the mixture was poured into diethyl ether (200 cm3) filtered through Celite and the filtrate washed in turn with dilute sulfuric acid (1.0 M; 2 times; 100 cm3) water (2 times; 100 cm3) and saturated brine (100 cm3) and then dried (Na2SO4) and evaporated.The residue was chromatographed on a column of silica gel in ethyl acetatendash;light petroleum (1 19) to yield 1468 J. Chem. Soc. Perkin Trans. 1 1997 2,4,7,9,13-pentamethyl-9-phenylethynyl-7,10-ethenospiro5.5- undeca-1,4-diene-3,8-dione 16 (0.89 g 41) as pale yellow crystals (from ethyl acetatendash;light petroleum) mp 132ndash;133 8C (Found C 84.4; H 7.2. C26H26O2 requires C 84.3; H 7.1); dH(CDCl3) 0.98 (3 H s 7-Me) 1.55 (3 H s 9-Me) 1.80 (1 H dd J 14.2 3.0 11-H) 1.85 (3-H d J 1.5 4-Me) 1.89 (3 H J 1.0 2-Me) 2.00 (3-H d J 1.7 13-Me) 2.70 (1 H dd J 14.2 2.5 11-H) 2.83 (1 H m 10-H) 5.47 (1 H dq J 1.7 1.2 12-H) 6.46 (1 H dq J 3.3 1.0 1-H) 6.82 (1 H dq J 3.3 1.5 5-H) 7.28ndash;7.35 (3 H m phenyl-H) and 7.39ndash;7.43 (2 H m phenyl- H); dC(CDCl3) 13.6 (7-Me) 16.1 (9-Me) 16.4 (9-Me or 13-Me) 21.8 (4-Me) 25.3 (2-Me) 33.6 (C-11) 44.4 (C-6) 48.0 (C-9) 48.4 (C-10) 55.5 (C-7) 84.4 (C C) 90.7 (C C) 122.6 (phenyl C-1) 124.1 (C-12) 128.3 (phenyl C-4) 128.4 (phenyl C-3 and C-5) 131.5 (phenyl C-2 and C-6) 134.5 (C-13) 135.2 (C-2) 146.1 (C-4) 147.9 (C-1) 148.0 (C-5) 186.7 (C-3) and 208.0 (C-8); nmax(CHCl3)/cm21 1727 1686 1633 1491 1449 1378 and 1231; lmax(EtOH)/nm 254 and 243 (e/dm3 mol21 cm21 26 480 and 27 690); m/z (370 1) 236 (62) 235 (30) 221 (54) 207 (25) 193 (85) 192 (50) 191 (30) 179 (18) 178 (64) 165 (31) 135 (33) 134 (100) 115 (24) 106 (20) 105 (32) 91 (94) 77 (35) 65 (26) and 63 (20).Crystal structure analysis of the spirocyclohexa-2,5-dienone 16 For diffractrometry a crystal was mounted on a glass fibre with cyanoacrylate resin.Lattice parameters at 21 8C were determined by a least-squares fit to the setting parameters of 25 independent reflections measured and refined on an Enraf- Nonius CAD4F four-circle diffractometer employing graphite monochromated Mo-Ka radiation. Crystal data. Formula C26H26O2; M 370.49 monoclinic space group P21/n a 12.979(4) b 9.423(4) c 18.129(3) Aring;; b 108.32(2)8 V 2104.8(9) Aring;3 Z 4 Dc 1.169 g cm23 m(Mo-Ka) 0.39 cm21 l(Mo-Ka) 0.7107 Aring; F(000) 792 electrons. Data collection and processing. Intensity data were collected in the range 1 q 22.58 using an wndash;q scan. The scan widths and horizontal counter apertures employed were (1.00 1 0.35 tan q)8 and (2.70 1 1.05 tan q) mm respectively. Data reduction and application of Lorentz and polarisation corrections were carried out using the Enraf-Nonius Structure Determination Package.11 Of the 3060 reflections collected 889 with I 2.5s(I ) were considered observed and used in the calculations.Structure analysis and refinement. The structure was solved by direct methods using SHELXS-8612 and the solution was extended by difference Fourier methods. The phenyl group was included as a rigid group (CC 1.395 Aring;) with isotropically refined thermal parameters hydrogen atoms were included at calculated sites (CH 0.97 Aring;) and all other atoms were refined anisotropically. The use of these constraints allowed for a satisfactory refinement despite the small number of observed reflections available from the small and weakly diffracting crystals.Full-matrix least-squares refinement of an overall scale factor positional and thermal parameters converged (all shifts 0.07s) with Rdagger; 0.052 Rw 0.051 and w = 2.19/ s2(Fo) 1 0.000 11Fo 2. Maximum excursions in a final difference map were 10.2 e Aring;23 and 20.2 e Aring;23. Scattering factors and anomalous dispersion terms used were those supplied in SHELX-76.13 All calculations were carried out using SHELX- 76 13 and plots were drawn using ORTEP.14 The atom numbering scheme is given in Fig. 1. Atomic coordinates bond lengths and bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre. See Instructions for Authors (1997) J. Chem. Soc. Perkin Trans. 1 1997 Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 207/99.Acknowledgements This work was supported by a grant from the Australian Research Council. C. J. P. gratefully acknowledges receipt of an Australian Postgraduate Award. References 1 M. G. Moloney J. T. Pinhey and E. G. Roche Tetrahedron Lett. 1986 27 5025; M. G. Moloney J. T. Pinhey and E. G. Roche J. Chem. Soc. Perkin Trans. 1 1989 333. 2 S.-I. Hashimoto Y. Miyazaki T. Shinoda and S. Ikegami J. Chem. Soc. Chem. Commun. 1990 1100. 3 J. T. Pinhey and E. G. Roche J. Chem. Soc. Perkin Trans. 1 1988 2415. 4 C. J. Parkinson and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1991 1053. 5 S. I. Hashimoto T. Shinoda and S. Ikegami J. Chem. Soc. Chem. Commun. 1988 1137. 6 J. Morgan and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1990 715. 7 H. C.Bell J. T. Pinhey and S. Sternhell Aust. J. Chem. 1979 32 1551. 8 T. W. Hambley R. J. Holmes C. J. Parkinson and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1992 1917. 9 J. Morgan T. W. Hambley and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1996 2173. 10 G. A. Russell M. Jawdosiuk and M. Makosza J. Am. Chem. Soc. 1979 101 2355. 11 Enraf-Nonius Structure Determination Package Enraf-Nonius Delft 1985. 12 G. M. Sheldrick in Crystallographic Computing 3 eds G. M. Sheldrick C. Kruger and R. Goddard Oxford University Press 1985 pp 175ndash;189. 13 G. M. Sheldrick SHELX-76 A Program for Crystal Structure Determination University of Cambridge 1976. 14 C. K. Johnson ORTEP A Thermal Ellipsoid Plotting Program Oak Ridge National Laboratories Oak Ridge 1965. Paper 6/08582B Received 23rd December 1996 Accepted 29th January 1997 dagger; R = S(verbar;verbar;Foverbar; 2 verbar;Fcverbar;verbar;)/Sverbar;Foverbar; Rw = Sw(verbar;Foverbar; 2 verbar;Fcverbar;)2/Swo 2� �� .J. Chem. Soc. Perkin Trans. 1 1997 1465 The in situ generation of alk-1-ynyllead triacetates from terminal acetylenes by zincndash;lead exchange and crystal structure of 2,4,7,9,13- pentamethyl-9-phenylethynyl-7,10-ethenospiro5.5undeca-1,4-diene- 3,8-dione Christopher J. Parkinson Trevor W. Hambley and John T. Pinhey * School of Chemistry University of Sydney Sydney 2006 Australia Methods involving zincndash;lead exchange for the one-pot conversion of terminal acetylenes into alk-1- ynyllead(IV) triacetates have been developed and examples of the in situ C-alkynylation of a number of carbon nucleophiles are reported. An attempt to extend the reaction to phenols by treating 2,4,6- trimethylphenol with phenylethynyllead triacetate led to formation of the spiro dienone 16 the structure of which was determined by X-ray diffraction.In an earlier paper we reported a new general method for the Calkynylation of soft carbon nucleophiles such as b-dicarbonyl compounds and sodium nitronates.1 The procedure involved the treatment of the nucleophile with an alk-1-ynyllead triacetate unstable compounds which may be produced in solution by the reaction of either an alk-1-ynyl(trimethyl)stannane or a di(alk-1-ynyl)mercury compound with lead tetraacetate (LTA) (Scheme 1). The development of a one-pot procedure for converting an acetylene into an alkynyllead triacetate in situ was recognised by us as a potentially useful extension of the method especially because of the moisture sensitivity of alk-1-ynyl(trimethyl)- stannanes.Such a method was later reported by Ikegami,2 who found that if a tetrahydrofuran solution of a lithium acetylide was added at low temperature to LTA in methylene dichloride the resulting mixture reacted at room temperature with a range of b-keto benzyl esters to give good yields of the corresponding a-alkynylated keto esters. We have attempted to use this procedure to produce the a-hex-1-ynyl b-keto ester 11; however we found that reaction of ethyl 2-oxocyclopentanecarboxylate 1 under the conditions reported resulted in formation of the dimer 2 in approximately 72 yield and recovery of about 9 of the keto ester 1 (see Scheme 2). None of the hexynyl derivative 11 could be detected in the reaction mixture. Compound 2 is readily formed by treatment of the b-keto ester 1 with LTA,3 which would indicate that the relatively fast disproportionation of the alkynyllead triacetate to the tetraalkynyllead and LTA Scheme 1 Scheme 2 Reagents and conditions i Mixture from reaction of C4H9C CLi and Pb(OAc)4 at 220 8C then 15 min at RT; ii Pb(OAc)4 which we had noted previously,1 had occurred eqn.(1). This would suggest that in the case of the b-keto ether 1 alkynylation is slower than for the corresponding benzyl ester. In previous work it has been noted by ourselves 4 and by Ikegami and co-workers 5 that the reactivity of b-keto esters towards organolead triacetates is dependent on the nature of the ester group; methyl esters and benzyl esters were found to be more reactive than ethyl esters. At about the same time as the communication of Ikegami we had found that alkynylzinc chlorides reacted with LTA to give a solution which had the capacity to carry out the electrophilic alkynylation of b-keto esters.This reaction which has been developed into a useful one-pot method for the C-alkynylation of soft carbon nucleophiles is outlined for the synthesis of the keto ester 3 (see Scheme 3). The most efficient and readily reproduced procedure which afforded a 73 yield of the phenylethynyl derivative 3 involved the treatment of phenylacetylene (1.2 mol equiv.) in tetrahydrofuran with butyllithium at 278 8C. Zinc chloride (1.2 mol equiv.) was added to the solution which was then stirred at 210 8C for 20 min. A solution of LTA (1.1 mol equiv.) in chloroform was then added at 210 8C to the solution which was then stirred for 15 s.After this the substrate 1 (1.0 mol equiv.) in chloroform was added to the mixture which was then stirred at 210 8C for 1 h and a further 2 h at room temperature. As we found previously in the case of Snndash;Pb and Hgndash;Pb exchange reactions,1 the time allowed for Znndash;Pb exchange is most important for the success of the reaction. This as indicated above is due to disproportionation of the alkynyllead triacetate which is outlined in eqn. (1). As can be seen from Table 1 the optimum yield of compound 3 was obtained after a Znndash;Pb exchange time of 15 s; any increase in this time resulted in formation of more of the dimer 4 and with a delay of 15 min Scheme 3 Reagents and conditions i BuLi THF 278 8C; ii ZnCl2; iii LTA CHCl3 210 8C then RT 0.25 min; iv compound 1 1466 J.Chem. Soc. Perkin Trans. 1 1997 before addition of the substrate 1 the product contained 33 of compound 4. The formation of the dimer 4 in the above reaction (Scheme 3) is noteworthy since the CO linked dimer 2 is the product of LTA oxidation of the keto ester 1.3 It appeared likely that the presence of zinc chloride caused the change in the mode of oxidative dimerisation and this was examined by treating the keto ester 1 with LTA (0.5 mol equiv.) and zinc chloride in chloroform. The CC linked dimer 4 was produced in 67 yield as a single diastereoisomer suggesting that the product arises in a radical coupling of two molecules complexed to a zinc ion through oxygen. In exploring the generality of the above one-pot alkynylation method the b-diketone 5 and the sodium nitronate 6 were found to react readily under the conditions indicated in Scheme 3 to give the phenylethynyl derivatives 7 and 9 in yields of 59 and 58 respectively.An initial attempt to extend the method by replacing phenylacetylene with oct-1-yne in Scheme 3 resulted in production of some of the expected keto ester 12; however there was significant dimer 4 formation. This problem was readily overcome by introducing a catalytic amount of mercury(II) acetate (0.1 mol equiv.) with the LTA and maintaining all other conditions as in Scheme 3. The modified method resulted in a 52 yield of the keto ester 12 and it would appear to be potentially useful for the introduction of a variety of alkynyl groups since the nucleophiles 5 and 6 behaved similarly to the b-keto ester 1 affording the octynyl derivatives 8 (52) and 10 (41) respectively in synthetically useful yields.Although yields in five of the six alkynylations were below those which we reported for alkynyllead triacetates generated for alkynyl(trimethyl)stannanes,1 the method offers greater effi- ciency in the use of the acetylene and its simplicity is a considerable advantage. The need to employ a catalytic amount of mercury(II) acetate for the octynylation reactions requires some comment. We had found in previous work6 that arylboronic acids react with LTA to give diaryllead diacetates whereas the same reaction conducted with a catalytic amount of mercury(II) acetate produced the aryllead triacetate in high yield. Thus we reasoned that the octynylzinc reagent may be reacting in a similar way with LTA to yield octynyllead triacetate and dioctynyllead diacetate but only the former lead compound with LTAndash;Hg(OAc)2.Thus in the absence of Hg(OAc)2 unchanged LTA would be available to produce the dimer 4. An attempt to extend the method to include the alkynylation of phenols was not successful and we attribute this to their lower reactivity towards organolead triacetates as found by us in earlier work.7ndash;9 When 2,4,6-trimethylphenol (mesitol) 13 was added to the mixture produced by use of the above conditions for Znndash;Pb exchange with phenylacetylene none of the 6- phenylethynyl dienone 14 (or its dimer) 8 was detected. The product of Wessely acetoxylation compound 15 was present in 11 yield (see Scheme 4); however the major product of the reaction was the novel spirodienone 16 the structure of which was determined by X-ray diffraction (see below).The pathway to compound 16 no doubt involves a Dielsndash;Alder condensation between the 6-phenylethynylcyclohexadienone 14 and the mesitol oxidation product 17 (see Scheme 5). This latter compound could arise by elimination of HX from either the 6-acetoxy- Table 1 Effect of Znndash;Pb exchange time on the ratio of the acetylene derivative 3 to dimer 4 in the reaction of Scheme 3 conducted at 210 8C Znndash;Pb exchange time (min) Molar ratio of (3) (4) Total yield () 0.25 0.5 2.0 15.0 9.5 1 8.1 1 4.3 1 2 1 88 83 75 78 cyclohexadienone 15 or the corresponding chloride as shown. The fact that compound 16 is obtained as a single diastereoisomer is readily explicable in terms of the least hindered approach of the dienophile in the condensation.A single-crystal X-ray analysis (see Experimental section) of the spiro compound 16 showed that the structure consists of neutral molecules packed with no contacts shorter than those expected on the basis of the van der Waals radii as shown in Fig. 1. There is a triple bond between C(19) and C(20) and double bonds between C(4) and C(5) C(9) and C(10) C(12) and C(13) C(2) and O(1) and between C(11) and O(2). The phenylacetylene and cyclohexa-2,5-dienone moieties are both planar to within 0.05 Aring;. Long bonds between C(3) and C(8) 1.61(1) Aring; and between C(7) and C(8) 1.57(1) Aring; reflect the strain about the quaternary atom C(8). Experimental Mps were determined on a Kofler hot-stage and are uncorrected. Column chromatography was carried out on Merck Kieselgel 60 (230ndash;240 mesh).IR spectra were recorded on a Digilab FTS-80 spectrometer and NMR spectra were deter- Scheme 4 Reagents and conditions i BuLi THF 278 8C; ii ZnCl2; iii LTA CHCl3 210 8C then RT 0.25 min; iv compound 13 Scheme 5 J. Chem. Soc. Perkin Trans. 1 1997 1467 mined with SiMe4 as internal standard on Bruker AMX-400 and AC-200B spectrometers. J Values are given in Hz. Microanalyses were performed by the microanalytical unit of the School of Chemistry University of New South Wales and mass spectra were recorded on an AEI model MS902 double focusing instrument. General method for the reaction of carbon nucleophiles with phenylethynyllead triacetate generated in situ by Znndash;Pb exchange Phenylacetylene (0.51 g 5.0 mmol) was dissolved in dry tetrahydrofuran (5 cm3). Butyllithium solution (2.0 M; 2.5 cm3 5.0 mmol) in hexane was added at 278 8C to the mixture which was then stirred for 20 min under nitrogen.Zinc chloride (0.68 g 5.0 mmol) was added to the mixture after which it was allowed to warm to 210 8C; after being stirred at 210 8C for 30 min the mixture was diluted with chloroform (20 cm3) at 210 8C. Lead tetraacetate (2.03 g 4.58 mol) in chloroform (20 cm3) was added to the mixture after which it was stirred at 210 8C for 15 s. The substrate (4.17 mmol) in chloroform (4 cm3) (for 1 and 5) or THF (8 cm3) (for 6) was added to the solution which was then stirred at 2108 for 1 h followed by 2 h at room temperature. The mixture was then poured into diethyl ether (200 cm3) filtered through Celite and evaporated to give the crude product. The following compounds were synthesised by the above method.(i) Ethyl 2-oxo-1-(phenylethynyl)cyclopentanecarboxylate 3 (0.78 g 73). Separated by HPLC (Whatman Partisil 10 M20) in ethyl acetatendash;light petroleum (1 49) as a colourless oil. It had 1H NMR and IR spectroscopic data in accord with literature values.1 (ii) 2-Acetyl-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)- one 7. Separated as an oil (0.71 g 59) by flash chromatography in ethyl acetatendash;light petroleum (1 19). The 1H NMR and IR spectra were identical with those obtained previously.1 (iii) 3-Methyl-3-nitro-1-phenylbut-1-yne 9. Obtained as an oil (0.46 g 58) by flash chromatography in ethyl acetatendash;light petroleum (1 19). The 1H NMR and IR spectra correspond with those obtained previously.1 General method for the reaction of carbon nucleophiles with oct- 1-ynyllead triacetate in situ by Znndash;Pb exchange Oct-1-yne (0.55 g 5.0 mmol) was dissolved in dry tetrahydrofuran (5 cm3).A solution of butyllithium (2.2 M; 2.25 ml 5.0 mmol) in hexane was added at 278 8C to the mixture which was then stirred for 20 min under nitrogen. Zinc chloride (0.68 g 5.0 mmol) was added to the solution after which it was Fig. 1 X-Ray molecular structure of spirocyclohexa-2,5-dienone 16 (with atomic numbering used in the crystallographic data) allowed to warm to 210 8C at which temperature it was stirred for 30 min; it was then diluted with chloroform (10 cm3) at 210 8C. Lead tetraacetate (2.03 g 4.58 mmol) and mercuric acetate (0.15 g 0.46 mmol) in chloroform (20 cm3) were added to the solution after which it was stirred at 210 8C for 15 s.The substrate (4.17 mmol) in chloroform (3 cm3) (for 1 and 5) or tetrahydrofuran (8 cm3) (for 6) was added to the solution which was then stirred at 210 8C for 1 h followed by 2 h at room temperature. The mixture was finally poured into diethyl ether (200 ml) filtered through Celite and evaporated to give the crude product. The following compounds were obtained by the above method. (i) Ethyl 1-(oct-1-ynyl)-2-oxocyclopentanecarboxylate 12. Separated by flash chromatography in ethyl acetatendash;light petroleum (7 95) as a colourless oil (0.57 g 52). The 1H NMR and IR specroscopic data were identical with those obtained previously.1 (ii) 2-Acetyl-2-(oct-1-ynyl)-3,4-dihydronaphthalen-1(2H)- one 8. Obtained by flash chromatography in ethyl acetatendash;light petroleum (1 19) as an oil (0.64 g 52).The 1H NMR and IR spectroscopic data were in accord with literature values.1 (iii) 2-Methyl-2-nitrodec-3-yne 10. Separated by flash chromatography in ethyl acetatendash;light petroleum (3 97) as an oil (0.34 g 41). The 1H NMR and IR spectroscopic data were identical with those previously reported.10 Oxidation of ethyl 2-oxocyclopentanecarboxylate 1 by LTA in the presence of ZnCl2 Lead tetraacetate (2.42 g 5.46 mol) in chloroform (10 cm3) was added to a solution of ethyl 2-oxocyclopentanecarboxylate (1.53 g 9.83 mmol) in chloroform (10 cm3) and tetrahydrofuran (10 cm3) at 210 8C and the mixture was stirred at 210 8C for 1 h followed by 2 h at room temperature. The mixture was then poured into diethyl ether (200 cm3) filtered through Celite and evaporated. The crude material was fractionated by flash chromatography (ethyl acetatendash;light petroleum 2 23) to yield the dimer 4 as a colourless oil (1.025 g 67) (Found C 61.7; H 7.4.C16H22O6 requires C 61.9; H 7.1); dH(CDCl3) 4.29 (4 H q J 7.1 2 times; CO2CH2CH3) 2.86ndash;2.72 (2 H dt J 14.1 10.4 3-H and 39-H) 2.71ndash;2.27 (6-H m 3-H 39-H 5-H2 and 59-H2) 2.26ndash; 2.07 (4-H m 4-H2 and 49-H2) and 1.32 (6 H t J 7.1 2 times; CO2CH2CH3); dC(CHCl3) 205.9 (C-2 and C-29) 166.9 (2 times; CO2Et) 69.4 (C-1 and C-19) 62.7 (2 times; CO2CH2CH3) 38.1 (C-3 and C-39) 35.0 (C-5 and C-59) 18.8 (2 times; CH3) and 13.6 (C-4 and C-49); nmax(CHCl3)/cm21 1768 and 1723; m/z 164 (M 2 2 times; CO2Et 13) 162 (26) 145 (13) 135 (25) 134 (18) 132 (14) 123 (13) 122 (26) 120 (20) 117 (28) 109 (66) 108 (34) 107 (76) 99 (32) 89 (28) 82 (41) 81 (26) 73 (20) and 55 (100). Reaction of 2,4,6-trimethylphenol (mesitol) 13 with phenylethynyllead triacetate produced by Znndash;Pb exchange Butyllithium in hexane (2.0 M; 3.5 cm3 7.06 mmol) was added to phenylacetylene (0.72 g 7.06 mmol) in dry THF (7.0 cm3) at 278 8C and the mixture was stirred for 20 min under N2.Zinc chloride (0.96 g 7.06 mmol) was added to the solution which was then allowed to warm to 210 8C at which temperature it was stirred for 30 min. Chloroform (25 cm3) was added to the mixture followed by LTA (2.84 g 6.42 mmol) in chloroform (25 cm3); the mixture was then stirred at 210 8C for 15 s. Mesitol 13 (0.80 g 5.88 mmol) in chloroform (6 cm3) and pyridine (1.01 g 12.8 mol) were then added to the mixture after which it was stirred at 210 8C for 1 h followed by 3 h at room temperature. After this the mixture was poured into diethyl ether (200 cm3) filtered through Celite and the filtrate washed in turn with dilute sulfuric acid (1.0 M; 2 times; 100 cm3) water (2 times; 100 cm3) and saturated brine (100 cm3) and then dried (Na2SO4) and evaporated.The residue was chromatographed on a column of silica gel in ethyl acetatendash;light petroleum (1 19) to yield 1468 J. Chem. Soc. Perkin Trans. 1 1997 2,4,7,9,13-pentamethyl-9-phenylethynyl-7,10-ethenospiro5.5- undeca-1,4-diene-3,8-dione 16 (0.89 g 41) as pale yellow crystals (from ethyl acetatendash;light petroleum) mp 132ndash;133 8C (Found C 84.4; H 7.2. C26H26O2 requires C 84.3; H 7.1); dH(CDCl3) 0.98 (3 H s 7-Me) 1.55 (3 H s 9-Me) 1.80 (1 H dd J 14.2 3.0 11-H) 1.85 (3-H d J 1.5 4-Me) 1.89 (3 H J 1.0 2-Me) 2.00 (3-H d J 1.7 13-Me) 2.70 (1 H dd J 14.2 2.5 11-H) 2.83 (1 H m 10-H) 5.47 (1 H dq J 1.7 1.2 12-H) 6.46 (1 H dq J 3.3 1.0 1-H) 6.82 (1 H dq J 3.3 1.5 5-H) 7.28ndash;7.35 (3 H m phenyl-H) and 7.39ndash;7.43 (2 H m phenyl- H); dC(CDCl3) 13.6 (7-Me) 16.1 (9-Me) 16.4 (9-Me or 13-Me) 21.8 (4-Me) 25.3 (2-Me) 33.6 (C-11) 44.4 (C-6) 48.0 (C-9) 48.4 (C-10) 55.5 (C-7) 84.4 (C C) 90.7 (C C) 122.6 (phenyl C-1) 124.1 (C-12) 128.3 (phenyl C-4) 128.4 (phenyl C-3 and C-5) 131.5 (phenyl C-2 and C-6) 134.5 (C-13) 135.2 (C-2) 146.1 (C-4) 147.9 (C-1) 148.0 (C-5) 186.7 (C-3) and 208.0 (C-8); nmax(CHCl3)/cm21 1727 1686 1633 1491 1449 1378 and 1231; lmax(EtOH)/nm 254 and 243 (e/dm3 mol21 cm21 26 480 and 27 690); m/z (370 1) 236 (62) 235 (30) 221 (54) 207 (25) 193 (85) 192 (50) 191 (30) 179 (18) 178 (64) 165 (31) 135 (33) 134 (100) 115 (24) 106 (20) 105 (32) 91 (94) 77 (35) 65 (26) and 63 (20).Crystal structure analysis of the spirocyclohexa-2,5-dienone 16 For diffractrometry a crystal was mounted on a glass fibre with cyanoacrylate resin. Lattice parameters at 21 8C were determined by a least-squares fit to the setting parameters of 25 independent reflections measured and refined on an Enraf- Nonius CAD4F four-circle diffractometer employing graphite monochromated Mo-Ka radiation. Crystal data. Formula C26H26O2; M 370.49 monoclinic space group P21/n a 12.979(4) b 9.423(4) c 18.129(3) Aring;; b 108.32(2)8 V 2104.8(9) Aring;3 Z 4 Dc 1.169 g cm23 m(Mo-Ka) 0.39 cm21 l(Mo-Ka) 0.7107 Aring; F(000) 792 electrons. Data collection and processing. Intensity data were collected in the range 1 q 22.58 using an wndash;q scan. The scan widths and horizontal counter apertures employed were (1.00 1 0.35 tan q)8 and (2.70 1 1.05 tan q) mm respectively.Data reduction and application of Lorentz and polarisation corrections were carried out using the Enraf-Nonius Structure Determination Package.11 Of the 3060 reflections collected 889 with I 2.5s(I ) were considered observed and used in the calculations. Structure analysis and refinement. The structure was solved by direct methods using SHELXS-8612 and the solution was extended by difference Fourier methods. The phenyl group was included as a rigid group (CC 1.395 Aring;) with isotropically refined thermal parameters hydrogen atoms were included at calculated sites (CH 0.97 Aring;) and all other atoms were refined anisotropically. The use of these constraints allowed for a satisfactory refinement despite the small number of observed reflections available from the small and weakly diffracting crystals.Full-matrix least-squares refinement of an overall scale factor positional and thermal parameters converged (all shifts 0.07s) with Rdagger; 0.052 Rw 0.051 and w = 2.19/ s2(Fo) 1 0.000 11Fo 2. Maximum excursions in a final difference map were 10.2 e Aring;23 and 20.2 e Aring;23. Scattering factors and anomalous dispersion terms used were those supplied in SHELX-76.13 All calculations were carried out using SHELX- 76 13 and plots were drawn using ORTEP.14 The atom numbering scheme is given in Fig. 1. Atomic coordinates bond lengths and bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre. See Instructions for Authors (1997) J.Chem. Soc. Perkin Trans. 1 1997 Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 207/99. Acknowledgements This work was supported by a grant from the Australian Research Council. C. J. P. gratefully acknowledges receipt of an Australian Postgraduate Award. References 1 M. G. Moloney J. T. Pinhey and E. G. Roche Tetrahedron Lett. 1986 27 5025; M. G. Moloney J. T. Pinhey and E. G. Roche J. Chem. Soc. Perkin Trans. 1 1989 333. 2 S.-I. Hashimoto Y. Miyazaki T. Shinoda and S. Ikegami J. Chem. Soc. Chem. Commun. 1990 1100. 3 J. T. Pinhey and E. G. Roche J. Chem. Soc. Perkin Trans. 1 1988 2415. 4 C. J. Parkinson and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1991 1053. 5 S. I. Hashimoto T. Shinoda and S. Ikegami J. Chem.Soc. Chem. Commun. 1988 1137. 6 J. Morgan and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1990 715. 7 H. C. Bell J. T. Pinhey and S. Sternhell Aust. J. Chem. 1979 32 1551. 8 T. W. Hambley R. J. Holmes C. J. Parkinson and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1992 1917. 9 J. Morgan T. W. Hambley and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1996 2173. 10 G. A. Russell M. Jawdosiuk and M. Makosza J. Am. Chem. Soc. 1979 101 2355. 11 Enraf-Nonius Structure Determination Package Enraf-Nonius Delft 1985. 12 G. M. Sheldrick in Crystallographic Computing 3 eds G. M. Sheldrick C. Kruger and R. Goddard Oxford University Press 1985 pp 175ndash;189. 13 G. M. Sheldrick SHELX-76 A Program for Crystal Structure Determination University of Cambridge 1976. 14 C. K. Johnson ORTEP A Thermal Ellipsoid Plotting Program Oak Ridge National Laboratories Oak Ridge 1965.Paper 6/08582B Received 23rd December 1996 Accepted 29th January 1997 dagger; R = S(verbar;verbar;Foverbar; 2 verbar;Fcverbar;verbar;)/Sverbar;Foverbar; Rw = Sw(verbar;Foverbar; 2 verbar;Fcverbar;)2/Swo 2� �� . J. Chem. Soc. Perkin Trans. 1 1997 1465 The in situ generation of alk-1-ynyllead triacetates from terminal acetylenes by zincndash;lead exchange and crystal structure of 2,4,7,9,13- pentamethyl-9-phenylethynyl-7,10-ethenospiro5.5undeca-1,4-diene- 3,8-dione Christopher J. Parkinson Trevor W. Hambley and John T. Pinhey * School of Chemistry University of Sydney Sydney 2006 Australia Methods involving zincndash;lead exchange for the one-pot conversion of terminal acetylenes into alk-1- ynyllead(IV) triacetates have been developed and examples of the in situ C-alkynylation of a number of carbon nucleophiles are reported.An attempt to extend the reaction to phenols by treating 2,4,6- trimethylphenol with phenylethynyllead triacetate led to formation of the spiro dienone 16 the structure of which was determined by X-ray diffraction. In an earlier paper we reported a new general method for the Calkynylation of soft carbon nucleophiles such as b-dicarbonyl compounds and sodium nitronates.1 The procedure involved the treatment of the nucleophile with an alk-1-ynyllead triacetate unstable compounds which may be produced in solution by the reaction of either an alk-1-ynyl(trimethyl)stannane or a di(alk-1-ynyl)mercury compound with lead tetraacetate (LTA) (Scheme 1). The development of a one-pot procedure for converting an acetylene into an alkynyllead triacetate in situ was recognised by us as a potentially useful extension of the method especially because of the moisture sensitivity of alk-1-ynyl(trimethyl)- stannanes.Such a method was later reported by Ikegami,2 who found that if a tetrahydrofuran solution of a lithium acetylide was added at low temperature to LTA in methylene dichloride the resulting mixture reacted at room temperature with a range of b-keto benzyl esters to give good yields of the corresponding a-alkynylated keto esters. We have attempted to use this procedure to produce the a-hex-1-ynyl b-keto ester 11; however we found that reaction of ethyl 2-oxocyclopentanecarboxylate 1 under the conditions reported resulted in formation of the dimer 2 in approximately 72 yield and recovery of about 9 of the keto ester 1 (see Scheme 2).None of the hexynyl derivative 11 could be detected in the reaction mixture. Compound 2 is readily formed by treatment of the b-keto ester 1 with LTA,3 which would indicate that the relatively fast disproportionation of the alkynyllead triacetate to the tetraalkynyllead and LTA Scheme 1 Scheme 2 Reagents and conditions i Mixture from reaction of C4H9C CLi and Pb(OAc)4 at 220 8C then 15 min at RT; ii Pb(OAc)4 which we had noted previously,1 had occurred eqn. (1). This would suggest that in the case of the b-keto ethyl ester 1 alkynylation is slower than for the corresponding benzyl ester. In previous work it has been noted by ourselves 4 and by Ikegami and co-workers 5 that the reactivity of b-keto esters towards organolead triacetates is dependent on the nature of the ester group; methyl esters and benzyl esters were found to be more reactive than ethyl esters.At about the same time as the communication of Ikegami we had found that alkynylzinc chlorides reacted with LTA to give a solution which had the capacity to carry out the electrophilic alkynylation of b-keto esters. This reaction which has been developed into a useful one-pot method for the C-alkynylation of soft carbon nucleophiles is outlined for the synthesis of the keto ester 3 (see Scheme 3). The most efficient and readily reproduced procedure which afforded a 73 yield of the phenylethynyl derivative 3 involved the treatment of phenylacetylene (1.2 mol equiv.) in tetrahydrofuran with butyllithium at 278 8C. Zinc chloride (1.2 mol equiv.) was added to the solution which was then stirred at 210 8C for 20 min.A solution of LTA (1.1 mol equiv.) in chloroform was then added at 210 8C to the solution which was then stirred for 15 s. After this the substrate 1 (1.0 mol equiv.) in chloroform was added to the mixture which was then stirred at 210 8C for 1 h and a further 2 h at room temperature. As we found previously in the case of Snndash;Pb and Hgndash;Pb exchange reactions,1 the time allowed for Znndash;Pb exchange is most important for the success of the reaction. This as indicated above is due to disproportionation of the alkynyllead triacetate which is outlined in eqn. (1). As can be seen from Table 1 the optimum yield of compound 3 was obtained after a Znndash;Pb exchange time of 15 s; any increase in this time resulted in formation of more of the dimer 4 and with a delay of 15 min Scheme 3 Reagents and conditions i BuLi THF 278 8C; ii ZnCl2; iii LTA CHCl3 210 8C then RT 0.25 min; iv compound 1 1466 J.Chem. Soc. Perkin Trans. 1 1997 before addition of the substrate 1 the product contained 33 of compound 4. The formation of the dimer 4 in the above reaction (Scheme 3) is noteworthy since the CO linked dimer 2 is the product of LTA oxidation of the keto ester 1.3 It appeared likely that the presence of zinc chloride caused the change in the mode of oxidative dimerisation and this was examined by treating the keto ester 1 with LTA (0.5 mol equiv.) and zinc chloride in chloroform. The CC linked dimer 4 was produced in 67 yield as a single diastereoisomer suggesting that the product arises in a radical coupling of two molecules complexed to a zinc ion through oxygen.In exploring the generality of the one-pot alkynylation method the b-diketone 5 and the sodium nitronate 6 were found to react readily under the conditions indicated in Scheme 3 to give the phenylethynyl derivatives 7 and 9 in yields of 59 and 58 respectively. An initial attempt to extend the method by replacing phenylacetylene with oct-1-yne in Scheme 3 resulted in production of some of the expected keto ester 12; however there was significant dimer 4 formation. This problem was readily overcome by introducing a catalytic amount of mercury(II) acetate (0.1 mol equiv.) with the LTA and maintaining all other conditions as in Scheme 3. The modified method resulted in a 52 yield of the keto ester 12 and it would appear to be potentially useful for the introduction of a variety of alkynyl groups since the nucleophiles 5 and 6 behaved similarly to the b-keto ester 1 affording the octynyl derivatives 8 (52) and 10 (41) respectively in synthetically useful yields.Although yields in five of the six alkynylations were below those which we reported for alkynyllead triacetates generated for alkynyl(trimethyl)stannanes,1 the method offers greater effi- ciency in the use of the acetylene and its simplicity is a considerable advantage. The need to employ a catalytic amount of mercury(II) acetate for the octynylation reactions requires some comment. We had found in previous work6 that arylboronic acids react with LTA to give diaryllead diacetates whereas the same reaction conducted with a catalytic amount of mercury(II) acetate produced the aryllead triacetate in high yield.Thus we reasoned that the octynylzinc reagent may be reacting in a similar way with LTA to yield octynyllead triacetate and dioctynyllead diacetate but only the former lead compound with LTAndash;Hg(OAc)2. Thus in the absence of Hg(OAc)2 unchanged LTA would be available to produce the dimer 4. An attempt to extend the method to include the alkynylation of phenols was not successful and we attribute this to their lower reactivity towards organolead triacetates as found by us in earlier work.7ndash;9 When 2,4,6-trimethylphenol (mesitol) 13 was added to the mixture produced by use of the above conditions for Znndash;Pb exchange with phenylacetylene none of the 6- phenylethynyl dienone 14 (or its dimer) 8 was detected. The product of Wessely acetoxylation compound 15 was present in 11 yield (see Scheme 4); however the major product of the reaction was the novel spirodienone 16 the structure of which was determined by X-ray diffraction (see below).The pathway to compound 16 no doubt involves a Dielsndash;Alder condensation between the 6-phenylethynylcyclohexadienone 14 and the mesitol oxidation product 17 (see Scheme 5). This latter compound could arise by elimination of HX from either the 6-acetoxy- Table 1 Effect of Znndash;Pb exchange time on the ratio of the acetylene derivative 3 to dimer 4 in the reaction of Scheme 3 conducted at 210 8C Znndash;Pb exchange time (min) Molar ratio of (3) (4) Total yield () 0.25 0.5 2.0 15.0 9.5 1 8.1 1 4.3 1 2 1 88 83 75 78 cyclohexadienone 15 or the corresponding chloride as shown. The fact that compound 16 is obtained as a single diastereoisomer is readily explicable in terms of the least hindered approach of the dienophile in the condensation.A single-crystal X-ray analysis (see Experimental section) of the spiro compound 16 showed that the structure consists of neutral molecules packed with no contacts shorter than those expected on the basis of the van der Waals radii as shown in Fig. 1. There is a triple bond between C(19) and C(20) and double bonds between C(4) and C(5) C(9) and C(10) C(12) and C(13) C(2) and O(1) and between C(11) and O(2). The phenylacetylene and cyclohexa-2,5-dienone moieties are both planar to within 0.05 Aring;. Long bonds between C(3) and C(8) 1.61(1) Aring; and between C(7) and C(8) 1.57(1) Aring; reflect the strain about the quaternary atom C(8). Experimental Mps were determined on a Kofler hot-stage and are uncorrected.Column chromatography was carried out on Merck Kieselgel 60 (230ndash;240 mesh). IR spectra were recorded on a Digilab FTS-80 spectrometer and NMR spectra were deter- Scheme 4 Reagents and conditions i BuLi THF 278 8C; ii ZnCl2; iii LTA CHCl3 210 8C then RT 0.25 min; iv compound 13 Scheme 5 J. Chem. Soc. Perkin Trans. 1 1997 1467 mined with SiMe4 as internal standard on Bruker AMX-400 and AC-200B spectrometers. J Values are given in Hz. Microanalyses were performed by the microanalytical unit of the School of Chemistry University of New South Wales and mass spectra were recorded on an AEI model MS902 double focusing instrument. General method for the reaction of carbon nucleophiles with phenylethynyllead triacetate generated in situ by Znndash;Pb exchange Phenylacetylene (0.51 g 5.0 mmol) was dissolved in dry tetrahydrofuran (5 cm3).Butyllithium solution (2.0 M; 2.5 cm3 5.0 mmol) in hexane was added at 278 8C to the mixture which was then stirred for 20 min under nitrogen. Zinc chloride (0.68 g 5.0 mmol) was added to the mixture after which it was allowed to warm to 210 8C; after being stirred at 210 8C for 30 min the mixture was diluted with chloroform (20 cm3) at 210 8C. Lead tetraacetate (2.03 g 4.58 mol) in chloroform (20 cm3) was added to the mixture after which it was stirred at 210 8C for 15 s. The substrate (4.17 mmol) in chloroform (4 cm3) (for 1 and 5) or THF (8 cm3) (for 6) was added to the solution which was then stirred at 2108 for 1 h followed by 2 h at room temperature. The mixture was then poured into diethyl ether (200 cm3) filtered through Celite and evaporated to give the crude product.The following compounds were synthesised by the above method. (i) Ethyl 2-oxo-1-(phenylethynyl)cyclopentanecarboxylate 3 (0.78 g 73). Separated by HPLC (Whatman Partisil 10 M20) in ethyl acetatendash;light petroleum (1 49) as a colourless oil. It had 1H NMR and IR spectroscopic data in accord with literature values.1 (ii) 2-Acetyl-2-(phenylethynyl)-3,4-dihydronaphthalen-1(2H)- one 7. Separated as an oil (0.71 g 59) by flash chromatography in ethyl acetatendash;light petroleum (1 19). The 1H NMR and IR spectra were identical with those obtained previously.1 (iii) 3-Methyl-3-nitro-1-phenylbut-1-yne 9. Obtained as an oil (0.46 g 58) by flash chromatography in ethyl acetatendash;light petroleum (1 19). The 1H NMR and IR spectra correspond with those obtained previously.1 General method for the reaction of carbon nucleophiles with oct- 1-ynyllead triacetate in situ by Znndash;Pb exchange Oct-1-yne (0.55 g 5.0 mmol) was dissolved in dry tetrahydrofuran (5 cm3).A solution of butyllithium (2.2 M; 2.25 ml 5.0 mmol) in hexane was added at 278 8C to the mixture which was then stirred for 20 min under nitrogen. Zinc chloride (0.68 g 5.0 mmol) was added to the solution after which it was Fig. 1 X-Ray molecular structure of spirocyclohexa-2,5-dienone 16 (with atomic numbering used in the crystallographic data) allowed to warm to 210 8C at which temperature it was stirred for 30 min; it was then diluted with chloroform (10 cm3) at 210 8C. Lead tetraacetate (2.03 g 4.58 mmol) and mercuric acetate (0.15 g 0.46 mmol) in chloroform (20 cm3) were added to the solution after which it was stirred at 210 8C for 15 s.The substrate (4.17 mmol) in chloroform (3 cm3) (for 1 and 5) or tetrahydrofuran (8 cm3) (for 6) was added to the solution which was then stirred at 210 8C for 1 h followed by 2 h at room temperature. The mixture was finally poured into diethyl ether (200 ml) filtered through Celite and evaporated to give the crude product. The following compounds were obtained by the above method. (i) Ethyl 1-(oct-1-ynyl)-2-oxocyclopentanecarboxylate 12. Separated by flash chromatography in ethyl acetatendash;light petroleum (7 95) as a colourless oil (0.57 g 52). The 1H NMR and IR specroscopic data were identical with those obtained previously.1 (ii) 2-Acetyl-2-(oct-1-ynyl)-3,4-dihydronaphthalen-1(2H)- one 8.Obtained by flash chromatography in ethyl acetatendash;light petroleum (1 19) as an oil (0.64 g 52). The 1H NMR and IR spectroscopic data were in accord with literature values.1 (iii) 2-Methyl-2-nitrodec-3-yne 10. Separated by flash chromatography in ethyl acetatendash;light petroleum (3 97) as an oil (0.34 g 41). The 1H NMR and IR spectroscopic data were identical with those previously reported.10 Oxidation of ethyl 2-oxocyclopentanecarboxylate 1 by LTA in the presence of ZnCl2 Lead tetraacetate (2.42 g 5.46 mol) in chloroform (10 cm3) was added to a solution of ethyl 2-oxocyclopentanecarboxylate (1.53 g 9.83 mmol) in chloroform (10 cm3) and tetrahydrofuran (10 cm3) at 210 8C and the mixture was stirred at 210 8C for 1 h followed by 2 h at room temperature. The mixture was then poured into diethyl ether (200 cm3) filtered through Celite and evaporated.The crude material was fractionated by flash chromatography (ethyl acetatendash;light petroleum 2 23) to yield the dimer 4 as a colourless oil (1.025 g 67) (Found C 61.7; H 7.4. C16H22O6 requires C 61.9; H 7.1); dH(CDCl3) 4.29 (4 H q J 7.1 2 times; CO2CH2CH3) 2.86ndash;2.72 (2 H dt J 14.1 10.4 3-H and 39-H) 2.71ndash;2.27 (6-H m 3-H 39-H 5-H2 and 59-H2) 2.26ndash; 2.07 (4-H m 4-H2 and 49-H2) and 1.32 (6 H t J 7.1 2 times; CO2CH2CH3); dC(CHCl3) 205.9 (C-2 and C-29) 166.9 (2 times; CO2Et) 69.4 (C-1 and C-19) 62.7 (2 times; CO2CH2CH3) 38.1 (C-3 and C-39) 35.0 (C-5 and C-59) 18.8 (2 times; CH3) and 13.6 (C-4 and C-49); nmax(CHCl3)/cm21 1768 and 1723; m/z 164 (M 2 2 times; CO2Et 13) 162 (26) 145 (13) 135 (25) 134 (18) 132 (14) 123 (13) 122 (26) 120 (20) 117 (28) 109 (66) 108 (34) 107 (76) 99 (32) 89 (28) 82 (41) 81 (26) 73 (20) and 55 (100).Reaction of 2,4,6-trimethylphenol (mesitol) 13 with phenylethynyllead triacetate produced by Znndash;Pb exchange Butyllithium in hexane (2.0 M; 3.5 cm3 7.06 mmol) was added to phenylacetylene (0.72 g 7.06 mmol) in dry THF (7.0 cm3) at 278 8C and the mixture was stirred for 20 min under N2. Zinc chloride (0.96 g 7.06 mmol) was added to the solution which was then allowed to warm to 210 8C at which temperature it was stirred for 30 min. Chloroform (25 cm3) was added to the mixture followed by LTA (2.84 g 6.42 mmol) in chloroform (25 cm3); the mixture was then stirred at 210 8C for 15 s. Mesitol 13 (0.80 g 5.88 mmol) in chloroform (6 cm3) and pyridine (1.01 g 12.8 mol) were then added to the mixture after which it was stirred at 210 8C for 1 h followed by 3 h at room temperature.After this the mixture was poured into diethyl ether (200 cm3) filtered through Celite and the filtrate washed in turn with dilute sulfuric acid (1.0 M; 2 times; 100 cm3) water (2 times; 100 cm3) and saturated brine (100 cm3) and then dried (Na2SO4) and evaporated. The residue was chromatographed on a column of silica gel in ethyl acetatendash;light petroleum (1 19) to yield 1468 J. Chem. Soc. Perkin Trans. 1 1997 2,4,7,9,13-pentamethyl-9-phenylethynyl-7,10-ethenospiro5.5- undeca-1,4-diene-3,8-dione 16 (0.89 g 41) as pale yellow crystals (from ethyl acetatendash;light petroleum) mp 132ndash;133 8C (Found C 84.4; H 7.2. C26H26O2 requires C 84.3; H 7.1); dH(CDCl3) 0.98 (3 H s 7-Me) 1.55 (3 H s 9-Me) 1.80 (1 H dd J 14.2 3.0 11-H) 1.85 (3-H d J 1.5 4-Me) 1.89 (3 H J 1.0 2-Me) 2.00 (3-H d J 1.7 13-Me) 2.70 (1 H dd J 14.2 2.5 11-H) 2.83 (1 H m 10-H) 5.47 (1 H dq J 1.7 1.2 12-H) 6.46 (1 H dq J 3.3 1.0 1-H) 6.82 (1 H dq J 3.3 1.5 5-H) 7.28ndash;7.35 (3 H m phenyl-H) and 7.39ndash;7.43 (2 H m phenyl- H); dC(CDCl3) 13.6 (7-Me) 16.1 (9-Me) 16.4 (9-Me or 13-Me) 21.8 (4-Me) 25.3 (2-Me) 33.6 (C-11) 44.4 (C-6) 48.0 (C-9) 48.4 (C-10) 55.5 (C-7) 84.4 (C C) 90.7 (C C) 122.6 (phenyl C-1) 124.1 (C-12) 128.3 (phenyl C-4) 128.4 (phenyl C-3 and C-5) 131.5 (phenyl C-2 and C-6) 134.5 (C-13) 135.2 (C-2) 146.1 (C-4) 147.9 (C-1) 148.0 (C-5) 186.7 (C-3) and 208.0 (C-8); nmax(CHCl3)/cm21 1727 1686 1633 1491 1449 1378 and 1231; lmax(EtOH)/nm 254 and 243 (e/dm3 mol21 cm21 26 480 and 27 690); m/z (370 1) 236 (62) 235 (30) 221 (54) 207 (25) 193 (85) 192 (50) 191 (30) 179 (18) 178 (64) 165 (31) 135 (33) 134 (100) 115 (24) 106 (20) 105 (32) 91 (94) 77 (35) 65 (26) and 63 (20).Crystal structure analysis of the spirocyclohexa-2,5-dienone 16 For diffractrometry a crystal was mounted on a glass fibre with cyanoacrylate resin. Lattice parameters at 21 8C were determined by a least-squares fit to the setting parameters of 25 independent reflections measured and refined on an Enraf- Nonius CAD4F four-circle diffractometer employing graphite monochromated Mo-Ka radiation. Crystal data. Formula C26H26O2; M 370.49 monoclinic space group P21/n a 12.979(4) b 9.423(4) c 18.129(3) Aring;; b 108.32(2)8 V 2104.8(9) Aring;3 Z 4 Dc 1.169 g cm23 m(Mo-Ka) 0.39 cm21 l(Mo-Ka) 0.7107 Aring; F(000) 792 electrons. Data collection and processing.Intensity data were collected in the range 1 q 22.58 using an wndash;q scan. The scan widths and horizontal counter apertures employed were (1.00 1 0.35 tan q)8 and (2.70 1 1.05 tan q) mm respectively. Data reduction and application of Lorentz and polarisation corrections were carried out using the Enraf-Nonius Structure Determination Package.11 Of the 3060 reflections collected 889 with I 2.5s(I ) were considered observed and used in the calculations. Structure analysis and refinement. The structure was solved by direct methods using SHELXS-8612 and the solution was extended by difference Fourier methods. The phenyl group was included as a rigid group (CC 1.395 Aring;) with isotropically refined thermal parameters hydrogen atoms were included at calculated sites (CH 0.97 Aring;) and all other atoms were refined anisotropically.The use of these constraints allowed for a satisfactory refinement despite the small number of observed reflections available from the small and weakly diffracting crystals. Full-matrix least-squares refinement of an overall scale factor positional and thermal parameters converged (all shifts 0.07s) with Rdagger; 0.052 Rw 0.051 and w = 2.19/ s2(Fo) 1 0.000 11Fo 2. Maximum excursions in a final difference map were 10.2 e Aring;23 and 20.2 e Aring;23. Scattering factors and anomalous dispersion terms used were those supplied in SHELX-76.13 All calculations were carried out using SHELX- 76 13 and plots were drawn using ORTEP.14 The atom numbering scheme is given in Fig. 1. Atomic coordinates bond lengths and bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre.See Instructions for Authors (1997) J. Chem. Soc. Perkin Trans. 1 1997 Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 207/99. Acknowledgements This work was supported by a grant from the Australian Research Council. C. J. P. gratefully acknowledges receipt of an Australian Postgraduate Award. References 1 M. G. Moloney J. T. Pinhey and E. G. Roche Tetrahedron Lett. 1986 27 5025; M. G. Moloney J. T. Pinhey and E. G. Roche J. Chem. Soc. Perkin Trans. 1 1989 333. 2 S.-I. Hashimoto Y. Miyazaki T. Shinoda and S. Ikegami J. Chem. Soc. Chem. Commun. 1990 1100. 3 J. T. Pinhey and E. G. Roche J. Chem. Soc. Perkin Trans. 1 1988 2415. 4 C. J. Parkinson and J.T. Pinhey J. Chem. Soc. Perkin Trans. 1 1991 1053. 5 S. I. Hashimoto T. Shinoda and S. Ikegami J. Chem. Soc. Chem. Commun. 1988 1137. 6 J. Morgan and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1990 715. 7 H. C. Bell J. T. Pinhey and S. Sternhell Aust. J. Chem. 1979 32 1551. 8 T. W. Hambley R. J. Holmes C. J. Parkinson and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1992 1917. 9 J. Morgan T. W. Hambley and J. T. Pinhey J. Chem. Soc. Perkin Trans. 1 1996 2173. 10 G. A. Russell M. Jawdosiuk and M. Makosza J. Am. Chem. Soc. 1979 101 2355. 11 Enraf-Nonius Structure Determination Package Enraf-Nonius Delft 1985. 12 G. M. Sheldrick in Crystallographic Computing 3 eds G. M. Sheldrick C. Kruger and R. Goddard Oxford University Press 1985 pp 175ndash;189. 13 G. M. Sheldrick SHELX-76 A Program for Crystal Structure Determination University of Cambridge 1976.14 C. K. Johnson ORTEP A Thermal Ellipsoid Plotting Program Oak Ridge National Laboratories Oak Ridge 1965. Paper 6/08582B Received 23rd December 1996 Accepted 29th January 1997 dagger; R = S(verbar;verbar;Foverbar; 2 verbar;Fcverbar;verbar;)/Sverbar;Fo