J. CHEM. SOC. PERKIN TRANS. t 1995 Selective Elect rophi Iic Add itions of Mixed Bifunct iona Iized Trimet hylenemet hane Dian ion Synt hons George Majetich,' Hisaya Nishidie and Yong ZhangDepartment of Chemistry, The University of Georgia, Athens, Georgia, USA, 30602 Three trimethylenemethane dianion synthons showed upon the choice of catalyst employed. In 1979 Bates and co-workers showed that the dianion of isobutene 1 reacts with electrophiles to give functionalized open-chain compounds by first functionalizing one allylic anion and then adding an additional electrophiie to the remaining anion (c$ 1 -2, Scheme I).' When two electrophilic species I 13+ 21Scheme 1 are linked together, this dianion/dielectrophile strategy results in the formation of carbocyclic rings (cf 1-3).Unfortunately, reaction of the dianion 1 cannot be controlled to allow it to react successively with two different electrophiles, thus limiting this methodology. Allylstannanes and allylsilanes react with a wide variety of electrophiles, and these functionalities have been widely used as latent allylic nucleophiles for both inter- and intra- molecular carbon-carbon bond formation. Not surprisingly, these reactive functionalities have proven useful for numerous dianionic synthons of isobutene. For example, in 1983 Wuest and co-workers found that 2-methylidenepropane-1,3-diylbis-(triphenylstannane) 4 is slowly converted into 1,I, 1,5,5,5-a profound divergence of reactivity, based El,,AIBN,A Heal Ph3Sn SnPh3 4 oxallyl chkiride W(PPhJfinCI(33)n(.7 * 0A(3) R hexachloro-3-methylidenepentane5 in 65 yield via a radical 7 process eqn. (I).? Since then others have used related reagents for carbocyclic formation. Trost pioneered the use of trimethylenemethane equivalents, such as 6, for the one-step preparation of cyclopentane rings via 1,3-dipolar additions with electrophilic olefins eqn.(2).6Degl'Innocenti and co-workers showed that the allylbisstannane 7reacts with diacyl dichlorides to produce cyclic diones, independent of ring size {cf: 8 eqn. (3) and 12 eqn. (7)}.' Other workers have developed similar two- (3 + 31 step sequences differing only in the manner in which the various nucleophilic andlor electrophilic species are generated in situ.$*' Me3sY t Recently Keck and Ueno have found that bis-allylstannane reagents such as 4 react with standard electrophile~.~ 9 BuSnH (3oxoverall)$2-Trirnethylsilylrnethyl-rr-allylnickelhalides readily couple with alkyl nl.8halides to produce functionalized allyl~ilanes.~ Me? Me? R-X Me? R -Ni(COQp toluene X -CI. Br, I Rmorn tq. OAc 3omin NiBr pod Yields 3 + 31 r !l 10 11 13 + 41 10 (6) Me3Sn SnMe3 CI (65) ref. 7 0 7 12 0 Molander and Shubert have exploited mixed allylstannane,' allylsilane isobutene-based reagents for carbocyclic form- ation eqns. (5) and (6).In their studies, the allylic iodide 10 was treated with SnF, to generate a reactive allylstannane intermediate (cf 11) in situ, which then could be used for the preparation of five-, six-, seven-and/or eight-membered rings.'O During our study directed towards a synthesis of the linearly fused triquinane hirsutene we found that a trimethylallylsilane moiety reacts more rapidly under Lewis acid catalysis than the analogous methyldiphenylallylsilane.' This observation prompted us to prepare the mixed bifunctionalized reagents 13 and 14 on the premise that the differences in the reactivity of the functionalities present would allow us to control the order with which they react.$ Results and DiscussionF Reagents 13 and 14were prepared from 2-trimethylsilylmethyl- prop-2-en-1-01 (15)13as shown in eqn.(8) and Scheme 2, respectively.Reaction of the cuprate reagent derived from chloromethyldiphenylsilane l4 and iodide 10Is gave a 91yield of 3-methyldiphenylsilyl-2-C(trimethylsilyl)methylpropane 14. The preparation of 3-tributylstannyl-2-(trimethylsilyl)meth-10 14 Me3Sip 4 For rate constant comparing the reactivity of allylsilanes, silyl enol ethers and allylstannes, see ref. 12. 1 All yields are isolated yields. No attempt was made to optimize the transformations reported. J. CHEM. SOC. PERKIN TRANS. i 1995 S S Me3Si ?H Me3SI OLSMe Me3S! ?Me NaH, CSa Me1K Knefrom 151 15 16 17 ref. 16 t Me3Sf ?H Me3S/ Scheme 2 yllpropene 13 was less direct.11 Although reaction of the requisite cuprate reagent and the iodide 10 generated 13,its purification either chromatographically or by distillation was problematic.Fortunately, the reagent 13 could be prepared cleanly from either the dithiocarbamate 17 or the sulfide 18 (Scheme 2). Treatment of the alcohol 15 with sodium hydride and carbon disulfide, followed by the addition of iodomethane, produced the xanthate 16 which was thermally rearranged to 17.Conversion of this dithiocarbamate, or allylic sulfide 18, into the reagent 13 was achieved using a free radical process. Although less direct than the cuprate coupling, these alternative sequences allowed 13 to be prepared free of contaminants. We were confident that the differences in the reactivity of allylstannanes and allylsiianes would permit their differentiation in our bifunctional reagent.This conjecture proved to be valid. For example, trea'tment of mixed allylsilanejallylstannane 13 with fluoride ion resulted in the selective reaction of the allylsilane moiety (cf 19),since allylstannanes are inert under these conditions. In contrast, we observed that heating 13 at temperatures > 150 "Ccauses only the allylstannane moiety to react (cf 20).**This was not surprizing since allylstannanes are known to react at elevated temperatures,I6 whereas allysilanes are thermally stable.?? Me3Sj SnBu3 13 20 PhvBu3 OH 19 (9) Allylsilanes and allylstannanes both react with electrophiles on exposure to Lewis acid catalysts. We speculated that the more reactive nucleophilic functionality (the allylstannane) would react preferentially using a mild Lewis acid.Indeed, I( At first we made 3-trimethylsilyl-7-(trimethylstannyl)methylpro-pene by coupling the iodide 10 with (Me,Sn),CuI. In our hands, however, this product was difficult to purify, encouraging us to substitute the highly reactive trimethylstannyl moiety with a more stable tributylstannyl one. ** Extensive work showed that if reagent 13 was contaminated with organotin-by-products this condensation was not observed. tt Organostannanes also react under high pressure, see ref. 17. Our results suggest that reagent 13 should also exploit these experimental conditions. J. CHEM. SOC. PERKIN TRANS. I 1995 reaction of allylstannane/allylsilane 13with benzaldehyde in the presence of triethylaluminium, a weak Lewis acid, results in the selective reaction ofthe stannane moiety 13 -20, eqn.(lo). Me I SnBua Me3SII PhCHO, EIJAlK -78 +0°C 13 (42) 20 PhCHO. BFdtfl -78 +04: (57) SnBua 19 Stronger Lewis acids, such as titanium tetrachloride, stannous tetrachloride, iron trichloride, magnesium bromide, zinc chloride or trimethylsilyl triflate were also studied but gave unsatisfactory results. Inexplicably, the reaction of reagent 13 at low temperatures with a stoichiometric amount of boron trifluoride-diethyl ether resulted in the exclusive reaction of the allylsilane moiety (14 -19). The substrate 14 contains two allylsilane moieties, both of which will react with equal likelihood using fluoride ion catalysis but which we expected would demonstrate a Lewis acid dependency.This proved to be the case as treatment of 14 with trimethylaluminium resulted in the reaction of only the trimethylallylsilane unit cf: 21, eqn. (ll) leaving the less reactive methyldiphenylallylsilane unit for further use (i.e., 21 -22). Me3S SiPh2Me SiPhPMe PhCHO The selectivity demonstrated by these bifunctional reagents has considerable synthetic potential. For example, the use of these reagents for the formation of polycyclic systems by means of a tandem inter-Iintra-molecular strategy, as generalized in eqn. (1 2), is the focus of on-going work. Experimental General.-AIl reactions were run under an inert atmosphere of nitrogen and monitored by TLC analysis until the starting material was completely consumed.Unless otherwise indicated, all ethereal work-ups consisted of the following procedure: the reaction was quenched at room temperature with saturated aqueous ammonium chloride. The organic solvent was removed under reduced pressure on a rotary evaporator and the residue was taken up in diethyl ether, washed with brine and dried over anhydrous magnesium sulfate. Filtration, followed by concen- tration at reduced pressure on a rotary evaporator and at 1 Torr to constant weight, afforded a crude residue which was purified i M = Sn or Si by flash chromatography using NM silica gel 60 (230-400 mesh ASTM) and distilled reagent grade solvents. 'H and 13C NMR spectra were obtained on a Bruker 250 spectrometer at 250 MHz and at 62.7 MHz, respectively.Chemical shifts are reported relative of CDCI, as an internal standard; J values are recorded in Hz. Microanalysis was performed by Atlantic Microlab, Inc., Atlanta, GA. 3-Tributylsra~nyl-2-(trimethylsilyl)methyllpropene13.-(a) via Cuprate coupling. To tributyltin hydride (786 mm3,ff 2.83 mmol) in dry tetrahydrofuran (THF; 8 cm3) at 0 "C was added dropwise butyllithium (2.5 mol dm-3 in hexanes; 1.13 cm3, 2.83 mmol). The resulting mixture was stirred at 0 "C for 2 h, after which it was transferred (via a cannula) to a suspension of copper() cyanide (270 mg, 1.42 mmol) in dry THF (2 cm3) at 0 "C. After 30 min, the reaction mixture was diluted with dry THF (5 cm3), cooled to -10 OC, and treated with the iodide 10 in dry THF (3 cm3).The resulting mixture was stirred at -10 OC for 90 min after which it was quenched by being poured onto saturated aqueous ammonium chloride and saturated aqueous sodium carbonate (1 : 1; 8 cm3); it was then extracted with ether (3 x 25 cm3). The combined extracts were dried (MgSO,), filtered and concentrated. Purification of the residue by chromatography on silica gel (elution with hexanes) gave 13 (319 mg, 65) which was homogenous by TLC analysis (hexanes, R, 10 0.68, R, 13 0.87) (Found; C, 54.8; H, 10.3. CI9H,,SiSn requires C, 54.68; H, 10.14); dH250 MHz; CDCI, 0.04 9 H, s, (CH,),Si, 0.91 9 H, t, J 7, (CH,-CH2CH2CH,),, 1.20-1.78 20 H, m, (CH2CH2CH2CH3)3 and (CH,),SiCH,, 2.28 2 H, s, (CH3),SnCH2, 4.62 (1 H.s, HC=) and 4.72 (I H, s, HC=). (b) via Thedithiocarbamate route. The alcohol 15 (1.00 g, 6.93 mmol) was treated with sodium hydride (80; 229 mg, 7.62 mmol) dissolved in dry THF (15 cm3). Carbon sulfide (500 mm3, 8.32 mmol) was added to the mixture which was then stirred at 0 "C for 60 min. After this the mixture was treated with iodomethane (650 mm3, 10.40 mmol) and stirred for an additional 60 min at 0 "C. Standard ethereal work-up gave the crude xanthate (1.21 g; TLC analysis: hexane-ether, 10: 1, R, 15 0.21, RF 16 0.83) that was used without purification or characterization. The crude xanthate was dissolved in dry benzene (20 cm3) and the solution refluxed for 7 h. The reaction mixture was then cooled to room temperature, concentrated and chromato- graphed (elution with hexane-ether, 50: 1) to provide the dithiocarbamate 17 (I .27 g, 78) which was homogeneous by TLC analysis hexane-ether, 50: 1, R, 16 0.57, R, 17 0.401.The dithiocarbamate 17 (1.22 g, 5.18 mmol) was dissolved in toluene (20 cm3) and the solution heated to reflux. To the reaction mixture was added tributyltin hydride (1.41 dm3, 5.08 mmol) and azoisobutyronitrile (AIBN) (84 mg, 0.51 mmol) over a 30 rnin period. After the resulting mixture had been refluxed for 24 h it was evaporated under reduced pressure and the residue (2.59 g) was chromatographed on silica gel (elution hexanes, R, 17 0.18, R, 13 0.31) to give the reagent 13 (1.75 g, 81) which was identical with that prepared previously.(c) via The sulfide route. Ethanethiol (520 mm3, 7.01 mmol) was slowly added to butyllithium (2.5 mol drn-,; 3.0 cm3, 7.36 mmol) in THF (20 cm3) at 0 "C and the mixture then stirred for 30 min. The allylic iodide 10 was dissolved in dry THF (3 cm3) the solution added to the mixture over a 5-min period. The resulting mixture was stirred at 0 "C for 1 h and then warmed to room temperature over a 40-min period. Standard ethereal work-up, followed by chromatography (elution with hexanes), gave the sulfide 18 (1.03 g, 98) which was homogeneous by TLC analysis (hexanes, R, 10 0.74, R, 18 0.56); SH250 MHz; CDCl,, 0.03 9 H, s, (CH,),Si, 1.10 3 H, t, J 7, CH,(CH,), 1.70 2 H, s, (CH,),SiCH,, 2.22 (2 H, q, J 7, SCH,CH,), 3.10 (2 H, s, CHCH,S), 4.19 (1 H, s, HC=) and 4.36 (1 H, s, HG).The sulfide 18 (1.03 g, 5.47 mmol) was dissolved in toluene (30 cm3) and the resulting solution was heated to reflux. To the reaction mixture was added tributyltin hydride (1.49 cm3, 5.36 mmol) and AIBN (90 mg, 0.54 mmol) over a 30-min period. The resulting mixture was refluxed for 12 h after which it was evaporated under reduced pressure and the residue was chromatographed on silica gel (elution with hexanes) to give the reagent 13 (843 mg, 3773, identical with that previously described, 3-Methyldiphenylsilyl-2-(trimethylsilyl)niethyllpropene 14. -Phenyldimethylchlorosilane (3.50 g, 15.00 mmol) was added to finely cut lithium metal (250 mg, 36.00 mmol) suspended in dry THF (20 cm3). After being stirred for 90 rnin at -10 "C, the solution turned dark red. Continued vigorous stirring for 3 h produced a brownish solution which was transferred (via a cannula) to a suspension of copper(1) cyanide (600 mg, 6.70 mmol) in dry THF (5cm3) at 0 "C.After 30 rnin at -78 "C, the reaction mixture was allowed to warm to -10 "C. The iodide 10 (1.54 g, 6.70 mmol) in dry THF (5cm3) was added to it and the resulting mixture was stirred at -10 "C for 60 min. After this it was quenched by being poured onto a mixture of saturated aqueous ammonium chloride and saturated aqueous sodium carbonate (1 :I; 30 cm3) and extracted with ether (4 x 30 cm3 portions). The combined extracts were dried (MgSO,), filtered and concentrated.Purification of the residue by chromatography on silica gel (elution with hexanes) gave 14 (1.79 g, 91) which was homogeneous by TLC analysis (hexanes, RF 10 0.77, RF 14 0.61) (Found: C, 73.8; H, 8.7. CZ,H,,Si, requires C, 74.00; H, 8.69); 6,(250 MHz; CDC1,) 0.03 9 H. s, (CH,),Si, 0.66 3 H, s, CH,Si(C,H,),, 1.36 2 H, s, (CH3)$XH2, 2.09 2 H, s, CH,(C,H,),SiCH,, 4.45 (2 H, s, H,C=) and 7.35-7.65 lo H, m, (C6H5)J. Fluoride Ion-promoted Condensation of 13 with Benzalde- hyde.-To tetrabutylammonium fluoride trihydrate (3 13 mg, 1.20 mmol) which had been stored in uucuo for 30 rnin was added dry DMF (2 cm3) and a few activated 4 A molecular sieves. After 15 min, the solution was transferred to a reaction vessel containing 4 A molecular sieves (100 mg) and benz- aldehyde (55 mg, 0.90 mmol).The reagent 13 (417 mg, 1.00 mmol) in dry DMF (1 0 cm3) was added dropwise over 1 h using a syringe pump to the mixture which was then stirred at room temperature for 2 h and finally quenched with water. Standard ethereal work-up provided a crude residue that was purified by chromatography on silica gel (elution with hexanes-ether, 2 : 1) J. CHEM. SOC. PERKIN TRANS. I 1995 to afford the alcohol 19 (32.8 g, 73) which was homogeneous by TLC analysis (hexanes-ether, 1 : 1, R, PhCHO 0.79, R, 19 0.32); vm,,(film)/cm-l 3350-3200 (OH); 6,(250 MHz; CDC1,)0.929 H, t,J7,(CH2CH*CHZCH3)3, 1.20-1.7818 H, m, (CH,CH,CH,CH,),, 2.40-2.60 (1 H, m, CHCH,-C=), 2.42 (2 H, s, CH,SnR,), 3.72 (1 H, br s, OH), 4.81-4.90 (1 H, m, C~HSCHOH),5.00 (1 H, s, CH=), 5.20 (1 H, s, CH=) and 7.30- 7.50 (5 H, m, C,H,).Heat-promoted Condensation of 13 with Benzaldehyde. -To a solution of benzaldehyde (37 mg; 0.34 mmol) in dryp-xylene (3 cm3) was added the reagent 13 (100 mg, 0.34 mmol). After being refluxed for 24 h (1 50 "C), the reaction mixture was cooled to O"C, diluted with ether (25 cm3) and washed with saturated aqueous ammonium chloride. Standard ethereal work-up gave a crude residue which was purified by chromatography on silica gel (elution with hexanesther, 2 :1) to give the adduct 20 (49 mg, 61) which was homogeneous by TLC analysis (hexanes-ether, 1:1, R, PhCHO 0.79, R, 20 0.35); v,,,(film)/cm-' 3400-3150 (OH);6,(250 MHz; CDCI,) 0.07 9 H, s, (CH,),Si, 1.53-1.65 2 H, m, CH,Si(CH,),, 2.25-2.50(3 H, m, CH,C=and OH),4.70- 4.90 (3 H, m, CH,= and CHOH) and 7.20-7.50 (5 H, m, C,H,).Triethylaluminium-catalysedCondensation of 13 with Benz- aldehyde.-To a solution of benzaldehyde (1 59 mg, 1 .SO mmol) dry methylene dichloride (7 cm3) was added Et,Al (1.9 mol drn-,, 2.50 mmol) at -78 "C. After being stirred for 4 h at -78 "C, the reaction mixture was warmed to 0 OC and stirred at this temperature for 90 min. After this it was quenched with saturated aqueous ammonium chloride (2 cm3) and treated to a standard ethereal work-up to give a crude residue. This was purified by chromatography on silica gel (elution with hexanes- ether, 3 :1) to give the adduct 20 (24 mg, 42), identical with that prepared previously. BF,-Et,O-Catalysed Condensation of 13 with Benzalde-hyde.-To a solution of benzaldehyde (171 mg, 1.61 mmol) in dry methylene dichloride (7 cm3) was added BF,.Et,O (330 mm3, 2.8 mmol) at -78 OC.After being stirred for 3 h at -78 "C, the reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate (2 cm3) and subjected to a standard ethereal work-up to give a crude residue. This was purified by chromatography on silica gel (elution with hexanes- ether, 3:l) to give the adduct 19 (35 mg, 57) which was identical with that prepared previously. Et,AlCI-Catalysed Condensation of 14 and Benza1dehyde.- To a solution of benzaldehyde (444 mg, 4.18 mmol) and 14 (1.13 g, 3.48 mmol) in dry methylene dichloride (20 cm3) at -78 OC was added Et,AICI (1.93 cm3, 3.48 mmol).After being stirred for 1 h at -78 "C, the reaction mixture was quenched with saturated aqueous ammonium chloride (5 cm3) and subjected to a standard ethereal work-up to give a crude residue. This was purified by chromatography on silica gel (elution with hexanesxther, 3 : I) to give the alcohol 21 (522 mg, 42) which was homogeneous by TLC analysis (hexanes-ether, 3: 1, R, PhCHO 0.56; R, 21 0.36); 6,(250 MHz; CDCI,) 0.72 3 H, S, CH,Si(C,H,),, 2.20-2.50 (4 H, m, CH,CCH,), 4.77 (2 H, br s, CH,=), 7.20-7.70 lS H, m, (C6H,), and C6H5CH. Acerylation of 21.-To the alcohol 21 (522 mg, 1.46 mmol) dissolved in pyridine (2 cm3) was added acetic anhydride (1 cm3).The resulting mixture was stirred for 13 h at room temperature and then diluted with ether (50 cm3). The organic phase was washed with saturated aqueous copper(n) sulfate (3 x 50 cm3) and brine (15 cm3), dried (MgSO,), filtered and concentrated. The crude residue was chromatographed on silica gel (elution with hexanes*ther, 3 : 1) to furnish the acetate 22 J. CHEM SOC. PERKIN TRANS. I 1995 (558 mg, 95), which was homogeneous by TLC analysis (hexanes-ether, 3:1, R, 21 0.36; RF 22 0.69); 6,250 MHz; CDCI, 0.72 3 H, s, CH,Si(C,H,),, 2.12 (3 H, s, CH,CO), 3 I. Fleming, J. Dunogues and R. Smithers, Org. React., 1989,37, 57. 2.20-2.5514H,m,CH,CCH,),4.77(2H,brs,CH2=),5.92-6.054 S.Chandrasekhar, S.Latour, J.D. Wuest and B. Zacharie, J. Org. 2 For leading examples of allylstannane chemistry see: (a) Y. Yamamoto, Acc. Chem. Rex, 1987, 20, 243; (b)G. E. Keck and J. B. Yates, J. Am. Chem. Soc., 1982,104,5829. (1 H, m, CHOAc) and 7.20-7.75 I5 H, m, (C,H,), and C,H,CH. Fluoride Ion-promoted Condensation of 21 and Benzalde-hyde.-To tetrabutylammonium fluoride trihydrate (4.35mg, 1.67 mmol) which had been stored in vacuo for 30 min was added dry DMF (3 cm3) and a few activated 4 A molecular sieves. After 15 min, the solution was transferred to a reaction vessel containing 4 A molecular sieves (100 mg) and benz- aldehyde (1 33 mg, 1.25 mmol). A solution of acetate 22 (558 mg, 1.39 mmol) in dry DMF (10 cm3) was added dropwise to this solution over 1 h using a syringe pump.The resulting mixture was stirred at room temperature for 3 h and then quenched with water. Standard ethereal work-up provided a crude residue that was purified by chromatography on silica gel (elution with hexanes+ther, 3:l) to afford the alcohol 23 (375 mg, 87) which was homogeneous by TLC analysis hexanes展开▼
