Simple synthetic entries into the tricyclo5.3.1.13,9dodecane and 8-oxatetracyclo5.4.1.13,10.05,9tridecane ring systems

摘要

J. Chem. Soc. Perkin Trans. 1 1997 2937 Simple synthetic entries into the tricyclo5.3.1.13,9dodecane and 8-oxatetracyclo5.4.1.13,10.05,9tridecane ring systems Weimin Yue Roger Bishop,* Marcia L. Scudder and Donald C. Craig School of Chemistry The University of New South Wales Sydney 2052 Australia The bis(enolate) of diester 1 undergoes a double intramolecular alkylation reaction with 3-chloro-2- chloromethylprop-1-ene 2 to form the tricyclic product 3 in 75 yield. This conversion represents the first high-yielding route to derivatives of tricyclo5.3.1.13,9dodecane an alicyclic ring system of considerable theoretical and structural interest. Diol derivatives 5 7 10 16 and 17 are prepared to investigate further the crystal engineering requirements for obtaining new helical tubuland hosts.The X-ray structures of 5 10 and 7 reveal one- two- and three-dimensional hydrogen bonded lattice structures respectively despite their remarkable molecular similarity. Solid 5 comprises chains assembled through intermolecular ? ? ?HO? ? ?HO? ? ?HO? ? ? and novel intramolecular alkene ? ? ?HO hydrogen bonds; while diol 10 forms double layers of diols constructed from recurved spiral chains (four molecules per repeat unit) of intermolecular ? ? ?HO? ? ?HO? ? ?HO? ? ? hydrogen bonds. When crystallised from diethyl ether the hydroxy groups of 7 are linked ? ? ?HO? ? ?HO? ? ?HO? ? ? around threefold screw axes to give a further example of the helical tubuland lattice. This is a microporous solid with empty tubes of cross-sectional area 17.8 Å2 parallel to z. Appropriately functionalised tricyclo5.3.1.13,9dodecanes undergo efficient intramolecular cyclisation providing compounds 18 20 22 and 24 which are the first reported derivatives of 8-oxatetracyclo5.4.1.13,10.05,9tridecane.Introduction During the course of our continuing studies into the helical tubuland family of diol inclusion hosts 1 we required a convenient preparation of 2,5,8-trisubstituted tricyclo5.3.1.13,9- dodecane derivatives in order to investigate compounds such as 5 7 10 16 and 17. The closely related molecular structures of these diols fit the formal molecular rules required for potential helical tubuland lattice formation 2,3 and therefore were important target molecules. Relatively little work had been reported previously on syntheses of this alicyclic skeleton and none which could supply the necessary functionality at these three positions.This paper provides a simple solution to this problem and also describes the first derivatives of the previously unknown 8-oxatetracyclo5.4.1.13,10.05,9tridecane system. Results and discussion Synthetic entry to 2,5,8-trisubstituted tricyclo5.3.1.13,9- dodecanes Few synthetic data on tricyclo5.3.1.13,9dodecane (1,1-bishomoadamantane) derivatives have been published despite this ring system being of considerable interest from a theoretical viewpoint. Parker et al. 4 have predicted enhanced reactivity due to relief of angle strain at positions C3 and C7 in reactions leading to bridgehead carbocation or radical formation. Similarly the formation of bridgehead alkene derivatives is expected to be particularly favourable.Even the possible formation of bridgehead inside-pyramidalised hydrogen structures has been mooted.5 The 1,1-bishomoadamantane skeleton is therefore quite different in its behaviour to simpler homologues such as adamantane. These properties which are reflected in the difficulty of its synthesis arise because part of its skeleton comprises a bicyclo- 3.3.3undecane (manxane) sub-structure where flattening of the bridgehead sites creates significant strain.4 Hence preparative methods involving formation of the required eightmembered rings by closure methods are rarely effective although syntheses of double bridgehead 1,5-diaza- and 1,5- diphospha-manxanes have been most successful.6,7 The following approaches to the 1,1-bishomoadamantane skeleton have been reported. Adamantanone may be ring expanded easily into homoadamantan-4-one and this in turn subjected to Tiffeneau–Demjanov ring expansion which produced tricyclo5.3.1.13,9dodecan-4-one (15 yield).From this material Sasaki and co-workers were able to prepare several other 4-substituted derivatives and also the parent hydrocarbon but attempts to obtain the ring system through ring expansion of 3-tosyloxymethylhomoadamantane were unsuccessful.8 In an alternative approach Ag I-assisted hydrolysis of the dichlorocarbene adduct of homoadamant-4-ene gave a mixture of products including 5-chlorotricyclo5.3.1.13,9dodec-5-en-4- ol (30).9 Ward and Murray 10 used the route to tricyclo5.3.1.13,9- dodecan-4-one outlined above to prepare several bridgehead enolate derivatives and ultimately the bridgehead alkene itself in accord with the above ideas of favoured sp2 carbon hybridisation at this site.The final approach is our own whereby the bicyclic diester 1 11 was treated with sodium hydride in 1,2-dimethoxyethane and then refluxed with 1,3-dibromopropane affording 3,7- bis(methoxycarbonyl)tricyclo5.3.1.13,9dodecane-2,8-dione in 26 yield.12 Unfortunately this reaction is capricious isolation of pure product is difficult and the low yield obtained discourages further synthetic steps. Nonetheless we have used this approach to obtain helical tubuland diols containing this tricyclic skeleton and have studied their inclusion properties.1,13 It was therefore a welcome surprise that the corresponding double intramolecular alkylation of 1 using 3-chloro-2-chloromethylprop- 1-ene 2 14 (Scheme 1) afforded the required 5- substituted diester 3 cleanly and in excellent yield (75).Both Schulze et al.6 and Bell et al.15 have found the diiodo analogue of 2 to be an effective eight-membered ring-forming reagent in heteroatom cyclisations and the discovery of this efficient reaction now allows detailed investigation of the rare 1,1-bishomoadamantane ring system. Product 3 was fully characterised using conventional methods and several X-ray structures have been determined of compounds synthesised from it. Hence there is no doubt about the authenticity of this structural assignment even though its proton-decoupled 13C NMR spectrum in (CD3)2SO contained 2938 J. Chem. Soc. Perkin Trans. 1 1997 some unusual features. At 355 K the ten signals required for structure 3 appeared as sharp singlets at the expected d values.However at 300 K only six sharp singlets were observed. A further two broad peaks were present at d 58.8 (C) and 45.4 (CH2) and two very broad and extremely weak peaks at d 211.1 (C O) and 38.6 (CH2). These signals correspond to C3/C7 C4/ C6 C2/C8 and C11/C12 respectively. Clearly 3 is undergoing slow conformational motion at room temperature. This process will be examined in future work but similar effects were observed for other derivatives of this ring system. In fact the appearance of broad 13C NMR signals in room temperature spectra could be used here as a crude diagnostic indicator that new products actually did have this molecular skeleton. Syntheses of the 5-substituted tricyclo5.3.1.13,9dodecanediols 5 7 and 10 Removal of the methoxycarbonyl groups of 3 using simple acidic hydrolysis methods failed to yield the expected diketone 4 for reasons examined later.An alternative reaction heating with calcium iodide tetrahydrate in dimethyl sulfoxide following the method of Chang and co-workers,16,17 overcame this problem. Under carefully monitored conditions of temperature and reaction time a 64 conversion was obtained. Preferential attack of methyllithium on the more exposed exo-faces of 4 afforded the target 2,8-dimethyl-5-methylenetricyclo5.3.1.13,9- dodecane-2-syn,8-syn-diol 5 (Scheme 1). (In accord with our previous papers we designate hydroxy groups as syn- or antiwith respect to the larger of the bridges across the molecular twofold or pseudo-twofold axis.) Also as described later attempts to prepare diol 7 by direct catalytic reduction of 5 were not successful and therefore the dione 4 was reacted instead.Reduction of the alkene group proceeded slowly using H2–PtO2 (50 8C 45 psi) and took 3 days for completion. At this stage a 4 1 mixture of ketol and diol products was present from concomitant reduction of the carbonyl functionality. Jones’ oxidation gave the dione 6 in overall 95 yield and further reaction using methyllithium produced 2,5,8-trimethyltricyclo5.3.1.13,9dodecane-2-syn,8-syn-diol 7 (Scheme 2). Diol 10 is the double epimer of 7 and its preparation employed the methodology used previously in such circumstances. 1 Wittig reaction on dione 6 using the Dehmlow Scheme 1 1 COOCH3 CH3OOC OH HO COOCH3 CH3OOC O O NaH 75 CH2 CH2 Cl Cl + 3 2 O O CH2 4 5 CH3 H3C OH HO CH2 CH3Li CaI2•4H2O 64 70 1 2 3 4 5 6 7 8 9 10 11 12 method18 produced an excellent yield of the corresponding diene.Epoxidation of the more exposed exo-faces of 8 provided 9 which underwent reductive ring opening using LiAlH4 to provide 2,5,8-trimethyltricyclo5.3.1.13,9dodecane-2-anti,8-antidiol 10. Syntheses of the tricyclo5.3.1.13,9dodec-4-ene diols 16 and 17 The preparation of diol 16 (Scheme 3) commenced from dione 4 by protection of the carbonyl groups through reaction with ethylene glycol to give diketal 11. This reaction was catalysed by just one crystal of toluene-p-sulfonic acid since greater amounts Scheme 2 O O CH3 6 Ph3P=CH2 O O CH3 9 LiAlH4 7 CH3 H3C OH HO CH3 CH3 8 CH2 H2C MCPBA 90 85 10 CH3 H3C OH HO CH3 84 78 i H2 PtO2 ii Jones' reagent 95 4 CH3Li Scheme 3 4 O O CH2 11 O O O O 13 O O O O 12 O O O 14 O O 15 O N-NH-Ts 16 CH3 H3C OH HO O HOCH2CH2OH 81 O3 78 95 NH2NH-Ts CH3Li 56 H+ 100 CH3Li 77 O O J.Chem. Soc. Perkin Trans. 1 1997 2939 caused a significant degree of isomerisation of the alkene to the endo-isomer. Ozonolysis gave ketone 12 which was readily converted into its tosylhydrazone derivative 13. This reacted with methyllithium in a Shapiro reaction to yield the alkene 14. Finally compound 14 was deprotected in quantitative yield and then the resulting dione 15 alkylated using methyllithium to afford 2,8-dimethyltricyclo5.3.1.13,9dodec-4-ene-2-syn,8-syndiol 16. This diol was obtained as a colourless oil after column chromatography and as an amorphous semi-solid from pentane or hexane. Attempts to convert diol 5 to 7 through catalytic reduction using H2 and Pd/C were completely unsuccessful.An initial experiment conducted at ambient temperature and pressure in ethyl acetate solution gave 70 of the isomerised diol 17 and 30 of another compound (Scheme 4). These products were separated by column chromatography. 2,5,8-Trimethyltricyclo- 5.3.1.13,9dodec-4-ene-2-syn,8-syn-diol 17 was obtained as an oil and proved to be resistant to hydrogenation. A further experiment on 5 (50 8C 45 psi H2 3 days) still gave 17 as the major product and diol 7 eventually had to be prepared by the different method above. Syntheses of the 8-oxatetracyclo5.4.1.13,10.05,9tridecane derivatives 18 20 22 and 24 As noted above attempted reduction of diol 5 gave the isomerised diol 17 plus a 30 yield of a new and unexpected product.This compound was obtained quantitatively if the hydrogenation reaction was attempted in ethyl acetate solution using H2 and PtO2 with addition of two drops of 70 perchloric acid. Its 13C NMR data revealed loss of both the C2 symmetry and the alkene functionality present in the starting material. Microanalytical and mass spectral data showed that this product was isomeric and hence an additional ring must have been produced. Taking into account the other data available (see Experimental section) the cyclic ether structure 2,7,9- trimethyl-8-oxatetracyclo5.4.1.1 3,10.0 5,9tridecane-2-endo-ol 18 had been produced (Scheme 4). Models of diol 5 (and its crystal structure) show that the alkene group is in proximity to one of the two hydroxy groups so formation of 18 presumably involves an acid-catalysed intramolecular addition process.Other derivatives of this previously unreported ring system also could be obtained simply and in high yield. As related earlier acidic hydrolysis of diester 3 did not yield the expected product 4. Instead the hemiketal 9-hydroxy-7-methyl-8-oxatetracyclo 5.4.1.13,10.05,9tridecane-2-one 20 was produced in 90 yield (Scheme 5). Presumably loss of the ester groups was accompanied by hydration of the alkene group to produce the ketol 19 which then cyclised although no evidence for this equilibrium was visible from the 13C NMR spectrum of 20 in CDCl3. Similarly the hemiketal 2,9-dimethyl-8-oxatetracyclo- 5.4.1.13,10.05,9tridecane-2-endo,7-diol 22 was isolated in 80 yield (Scheme 6) from ozonolysis of diol 5 and no sign of an equilibrium with the open ketol structure 21 was apparent from solution NMR data.A fourth example of this class of compounds was obtained when diol 5 was reacted with m-chloroperbenzoic acid. The product was not the anticipated epoxide 23 but rather was Scheme 4 18 CH3 H3C O CH3 17 CH3 H3C OH HO CH3 30 70 5 CH3 H3C OH HO CH2 OH + H2 PtO2 HClO4 100 9 10 13 3 2 1 12 7 6 5 8 11 4 Pd/C H2 7-hydroxymethyl-2,9-dimethyl-8-oxatetracyclo5.4.1.13,10.05,9- tridecane-2-endo-ol 24 which was formed in 89 yield. This material is the formal result of an acid-catalysed epoxide ringopening where one hydroxy group of 23 has acted as an intramolecular nucleophile. The 13C NMR spectra of all four 8-oxatetracyclo- 5.4.1.13,10.05,9tridecane compounds showed sharp signals and were free of the line broadening effects observed earlier for the tricyclo5.3.1.13,9dodecane derivatives.This difference was a useful pointer to those reactions which had undergone intramolecular cyclisation to this new tetracyclic skeleton. Crystal structures of the diols 5 7 and 10 The X-ray structures of the three crystalline diols were determined and numerical details relating to these are presented in Table 1. Details of the solution and refinement of the structures are described in the Experimental section. Of these three candidate compounds only 7 exhibited any inclusion host properties. Discussion of crystal structure of 5. The molecular structure Scheme 5 COOCH3 CH3OOC O O CH2 O O CH3 O CH3 20 O HO HO 19 AcOH HCl 90 3 Scheme 6 5 CH3 H3C OH HO CH2 24 CH3 H3C 23 CH3 H3C OH HO O CH2OH O OH 21 CH3 H3C OH HO O 22 CH3 H3C O O3 OH OH 80 MCPBA 89 2940 J.Chem. Soc. Perkin Trans. 1 1997 Table 1 Numerical details of the solution and refinement of structures of diols 5 7 and 10 Compound Formula M Crystal description Space group a/Å b/Å c/Å b/8 V/Å3 T/8C Z Dc/g cm23 Radiation l/Å m/cm21 Crystal dimensions/mm Scan mode 2qmax/8 w scan angle No. of intensity measurements Criterion for observed reflection No. of independent obsd. reflections No. of reflections (m) and variables (n) in final refinement R = SmDF /SmFo Rw = SmwDF 2/SmwFo2� �� s = SmwDF 2/(m 2 n)� �� Crystal decay Max. min. transmission coefficients Largest peak in final diff. map/e Å23 Extinction coefficient R for (no. of) multiple measurements 5 C15H24O2 236.4 {100} {010} (12122) (1122) (2102) P21/c 7.707(2) 14.790(3) 12.615(3) 115.11(1) 1302.1(6) 21(1) 4 1.21 Cu-Ka 1.5418 5.73 0.19 × 0.16 × 0.45 q–2q 140 0.50 1 0.15 tan q 2700 I/s(I) > 3 1997 1997 161 0.051 0.087 3.35 1 to 0.93 0.92 0.83 0.26 5.34 × 1024 0.042 (178) 7 C15H2602 238.4 {100} (0021) (011) (1211) (0211) (2101) (2111) P3121 13.708(1) 13.708(1) 7.0046(8) (90) 1139.9(2) 21(1) 3 1.04 Cu-Ka 1.5418 4.91 0.35 × 0.35 × 0.36 q–2q 140 0.60 1 0.15 tan q 1613 I/s(I) > 3 1383 1383 90 0.037 0.058 2.50 1 to 0.96 0.87 0.85 0.25 — 0.012 (358) 10 C15H26O2 238.4 {010} {021} (2100) (11 028) P21/c 7.416(3) 23.175(6) 9.416(4) 123.28(1) 1353.0(9) 21(1) 4 1.17 Cu-Ka 1.5418 5.51 0.27 × 0.07 × 0.15 q–2q 120 0.60 1 0.15 tan q 2209 I/s(I) > 3 1209 1209 160 0.077 0.103 3.05 1 to 0.96 0.98 0.90 0.27 — 0.036 (168) and conformational arrangement of diol 5 is shown in Fig.1. Each molecule takes part in only two intermolecular HO? ? ?HO hydrogen bonds one at each of the two hydroxy groups such that the diols link together in chains along direction 2a1c with the hydrogen bonds following the sequence –donor–acceptor–acceptor– etc. Molecules in each chain have the enantiomeric sequence –A–B–A–B–A– etc. (where A and B represent the two enantiomers of 5) and these also have alternating orientations along the chain (Fig. 2). There are no particularly close contacts (C ? ? ? C 15) 320 (M1 5) 289 (28) 288 (72) 261 (23) 260 (39) 256 (18) 232 (19) 229 (39) 228 (40) 204 (15) 201 (30) 200 (31) 193 (17) 173 (31) 172 (20) 161 (20) 154 (17) 153 (29) 145 (38) 138 (15) 129 (17) 121 (16) 105 (15) 91 (26) 79 (22) 77 (27) 67 (17) 65 (29) 59 (100) 55 (92) 53 (45) 51 (20) 45 (33) 42 (32) 41 (52).5-Methylenetricyclo5.3.1.13,9dodecane-2,8-dione 4 Diester 3 (5.00 g 15.6 mmol) and calcium iodide tetrahydrate (5.68 g 15.6 mmol) were dissolved in dimethyl sulfoxide (30 cm3) in a flask set up for distillation. This mixture was stirred magnetically heated (7 h; oil bath at 185–190 8C) and volatile J.Chem. Soc. Perkin Trans. 1 1997 2943 material distilled over. The mustard yellow reaction residue was cooled to room temperature (rt) dissolved in water (50 cm3) and extracted using chloroform. The combined extracts were washed with HCl (1 mol dm23; ×3) saturated aqueous NaHCO3 (30 cm3) water (30 cm3) and then dried (Na2SO4). Evaporation of solvent from the filtrate gave a brown oil which was chromatographed on silica gel eluting with petrol and increasing proportions of diethyl ether. The product 4 was obtained as a white solid using 2 3 petrol–diethyl ether (2.04 g 64) mp 152–154 8C (from acetone) (Found C 76.1; H 8.15. C13H16O2 requires C 76.4; H 7.9); nmax(paraffin mull)/ cm21 3070w 1700s 1630w 1230m 1120m 1080w 1040m 1000m 960m 905m 795w 780w; dH(CDCl3) 4.83 (2H s) 2.96– 2.91 (2H m) 2.89–2.76 (2H m) 2.68 (2H br s) 2.27–2.04 (8H m); dC(CDCl3) 216.4 (C) 142.2 (C) 120.8 (CH2) 44.5 (CH) 43.5 (CH2) 43.3 (CH) 34.5 (CH2) 32.3 (CH2); m/z (>20) 204 (M1 100) 147 (24) 133 (32) 121 (25) 117 (27) 110 (22) 109 (56) 108 (57) 107 (47) 105 (36) 96 (87) 95 (82) 94 (36) 93 (39) 92 (25) 91 (85) 81 (34) 80 (27) 79 (95) 77 (65) 67 (37) 65 (25) 55 (72) 53 (34).2,8-Dimethyl-5-methylenetricyclo5.3.1.13,9dodecane-2-syn 8-syn-diol 5 Diketone 4 (1.40 g 6.85 mmol) was dissolved in THF (120 cm3; freshly distilled from LiAlH4) under dry N2 in a flask fitted with a condenser/drying tube and a septum. Methyllithium solution in diethyl ether (1.4 mol dm23; 14.7 cm3) was added dropwise to the solution at 0 8C using a syringe.The mixture was stirred at this temperature (1 h) then at rt (24 h). Damp diethyl ether was added cautiously followed by water (30 cm3). After 10 min the organic layer was separated the aqueous layer extracted using diethyl ether and the combined extracts dried (Na2SO4). Evaporation of solvent from the filtrate gave a milky oil which was purified by elution through silica gel eluting with petrol and increasing proportions of diethyl ether. The product 5 was obtained as a white solid using 1 1 petrol–diethyl ether (1.13 g 70) mp 133–134 8C (from diethyl ether) (Found C 76.5; H 10.6. C15H24O2 requires C 76.2; H 10.2); nmax(paraffin mull)/ cm21 3500s 3420s 3060w 1620m 1250m 1130s 1095m 1070m 1035m 1005m 980w 940s 890s 780w; dH(CDCl3) 4.96 (2H s) 3.00–2.95 (2H m) 2.44 (2H br s) 2.17–2.08 (4H m) 2.01–1.79 (6H m) 1.59–1.52 (2H m) 1.46 (6H s); dC(CDCl3) 152.7 (C) 116.6 (CH2) 74.1 (C) 39.4 (CH2) 39.2 (CH) 39.0 (CH) 32.9 (CH3) 31.0 (CH2) 28.1 (CH2); m/z (M1 and >10) 236 (M1 0.2) 200 (18) 185 (12) 145 (13) 143 (12) 131 (12) 121 (19) 120 (13) 119 (20) 117 (11) 109 (12) 108 (17) 107 (27) 106 (25) 105 (32) 95 (27) 94 (18) 93 (39) 92 (11) 91 (32) 81 (16) 79 (27) 77 (19) 71 (23) 67 (15) 55 (18) 53 (12) 43 (100).5-Methyltricyclo5.3.1.13,9dodecane-2,8-dione 6 Diketone 4 (1.00 g 4.90 mmol) was dissolved in ethyl acetate (30 cm3) and PtO2 (20 mg) added. The resulting mixture was shaken under a H2 atmosphere (45 psi; 50 8C; 2 d) on a hydrogenation apparatus. The reaction mixture was filtered through Celite and the solvent removed under reduced pressure to give a milky oil.This was dissolved in acetone (10 cm3) and reacted with excess Jones’ reagent (1.94 mol dm23; 3 cm3) in acetone initially at 0 8C and then at rt for 3 h. Water (20 cm3) was added followed by extraction with chloroform. The combined extracts were washed with saturated aqueous NaHCO3 then water and dried (Na2SO4). Evaporation of solvent from the filtrate gave a yellow oil which was purified by elution through silica gel eluting with petrol and increasing proportions of diethyl ether. The product 6 was obtained as a white solid using 1 1 petrol– diethyl ether (0.95 g 95) mp 102–103 8C (from petrol– diethyl ether) (Found C 75.6; H 8.7. C13H18O2 requires C 75.7; H 8.8); nmax(paraffin mull)/cm21 1690s 1250m 1235m 1190m 1105m 1080m 1050m 1020w 1000m 960w 780w 760w; dH(CDCl3) 2.92–2.86 (1H m) 2.74–2.59 (3H m) 2.27– 2.06 (5H m) 2.00–1.90 (2H m) 1.80–1.70 (1H m) 1.60–1.42 (2H m) 0.94–0.86 (1H m) 0.78 (3H d J 6.0); dC(CDCl3) 219.6 (C) 216.5 (C) 44.2 (CH) 44.0 (CH) 43.3 (CH2) 43.0 (CH) 42.8 (CH) 42.2 (CH2) 40.1 (CH2) 32.4 (CH2) 29.9 (CH2) 27.3 (CH or CH3) 24.4 (CH3 or CH); m/z (>10) 206 (M1 54) 178 (12) 163 (12) 150 (11) 149 (11) 145 (10) 137 (17) 136 (14) 135 (15) 131 (10) 124 (30) 123 (14) 122 (20) 121 (16) 111 (31) 110 (17) 109 (36) 108 (27) 107 (30) 105 (16) 97 (13) 96 (53) 95 (75) 94 (40) 93 (38) 92 (12) 91 (39) 83 (16) 82 (28) 81 (52) 80 (18) 79 (68) 77 (39) 69 (17) 68 (30) 67 (81) 65 (22) 55 (100) 53 (36) 51 (11) 43 (11).2,5,8-Trimethyltricyclo5.3.1.13,9dodecane-2-syn,8-syn-diol 7 Diketone 6 (0.95 g 4.61 mmol) was dissolved in THF (50 cm3; freshly distilled from LiAlH4) and reacted with methyllithium in diethyl ether solution (1.4 mol dm23; 10 cm3) using an identical procedure and work up to that used to obtain 5.Evaporation of solvent from the dried organic extracts gave a milky oil which was purified by elution through silica gel eluting with petrol and increasing proportions of diethyl ether. The product 7 was obtained as a white solid using 1 1 petrol–diethyl ether (0.75 g 68) mp 117–120 8C (from diethyl ether) (Found C 75.3; H 11.2. C15H26O2 requires C 75.6; H 11.0); nmax(paraffin mull)/ cm21 3400s 1220w 1180w 1120m 1080s 1020m 950m 920s 860m; dH(CDCl3) 2.30 (1H br m) 2.14–1.93 (4H m) 1.88–1.72 (2H m) 1.68–1.55 (5H m) 1.50–1.43 (2H m) 1.41–1.30 (2H m) 1.39 (3H s) 1.37 (3H s) 0.93 (1H t) 0.83 (3H d J 6.2); dC(CDCl3) 75.5 (C) 72.5 (C) 43.5 (CH2) 39.3 (two CH) 39.0 (CH) 38.4 (CH) 34.3 (CH3) 33.5 (CH3) 33.4 (CH2) 31.1 (CH2) 31.0 (CH2) 27.5 (CH) 25.6 (CH3) 25.4 (CH2); m/z (significant peaks and >20) 238 (M1 not observed) 223 (M 2 15)1 11 220 (M 2 18)1 8 202 (20) 177 (23) 149 (21) 147 (23) 146 (20) 145 (21) 135 (35) 125 (41) 121 (47) 119 (24) 109 (36) 108 (21) 107 (57) 105 (36) 95 (95) 94 (24) 93 (78) 92 (22) 91 (35) 81 (69) 79 (36) 77 (24) 71 (61) 69 (28) 67 (31) 55 (49) 43 (100).59-Methyldispirooxirane-2,29-tricyclo5.3.1.13,9dodecane-89,20- oxirane 9 Diketone 6 (0.45 g 2.18 mmol) methyltriphenylphosphonium bromide (1.95 g 5.45 mmol) and potassium tert-butoxide (0.61 g 5.54 mmol) were reacted in dry benzene (20 cm3) at 80 8C following the standard Wittig reaction and work up conditions devised by Dehmlow and Barahona-Naranjo.18 Triphenylphosphine oxide was filtered the solvent distilled off the concentrated residue eluted through silica gel using petrol and the solvent removed by distillation to give the diene 8 as a colourless oil (0.38 g 84) nmax(liquid film)/cm21 3050m 2900s 1620m 1440m 875s.A solution of m-chloroperbenzoic acid (MCPBA; 0.77 g of 80 purity 3.7 mmol) in dichloromethane (10 cm3) was added dropwise to a vigorously stirred mixture of diene 8 (0.37 g 1.8 mmol) and aqueous sodium hydrogen carbonate (0.5 mol dm23; 5.3 cm3). Stirring was continued for 4 h at rt then aqueous Na2S was added to destroy remaining peracid. The organic layer was separated the aqueous layer was extracted using dichloromethane and the combined extracts washed with water then dried (Na2SO4).Evaporation of solvent from the filtrate gave a sticky colourless oil (0.45 g) which was purified by elution through silica gel using petrol and increasing proportions of diethyl ether to give the bis(epoxide) 9 as an oil (0.39 g 90) pure by 13C NMR spectroscopy nmax(liquid film)/cm21 3020w 1270w 1240m 1210w 1120w 1090w 1080w 1020w 945s 930s 890m 855s 795s 725s; dH(CDCl3) 2.70–2.50 (4H m) 2.30–2.15 (1H m) 2.05–1.59 (10H m) 1.55–1.42 (1H m) 1.42–1.10 (2H m) 0.91 (1H t J 12.3) 0.79 (3H d J 6.1); dC(CDCl3) 65.5 61.4 52.5 52.1 44.0 40.7 35.2 34.9 (two peaks) 34.8 34.7 30.4 27.6 27.2 25.3. 2,5,8-Trimethyltricyclo5.3.1.13,9dodecane-2-anti,8-anti-diol 10 The bis(epoxide) 9 (0.45 g 1.91 mmol) was dissolved in THF (25 cm3; freshly distilled from LiAlH4) LiAlH4 (0.10 g) was 2944 J.Chem. Soc. Perkin Trans. 1 1997 added and the mixture was stirred at rt overnight. Wet diethyl ether was added cautiously followed by careful addition of cold water. Organic solvents were evaporated under reduced pressure the aqueous solution extracted thoroughly using ethyl acetate and the combined extracts dried (Na2SO4). Evaporation of solvent from the filtrate gave a white solid which was recrystallised from ethyl acetate to yield 10 (0.38 g 85) mp 203–204 8C (Found C 75.8; H 10.7. C15H26O2 requires C 75.6; H 11.0); nmax(paraffin mull)/cm21 3320s 1250m 1215w 1085s 1040m 1020m 965w 890m 865m 790w 750w; dH(CDCl3) 2.40–2.21 (1H m) 2.19–1.74 (11H m) 1.71–1.57 (2H m) 1.55–1.27 (2H m) 1.39 (3H s) 1.25 (3H s) 1.02–0.85 (1H m) 0.81 (3H d J 6.15); dC(CDCl3) 75.6 (two peaks) 42.6 40.3 39.5 39.1 38.6 36.7 31.8 28.5 27.6 27.4 25.3 25.0 24.5; m/z (M1 and >10) 238 (M1 0.15) 220 (13) 205 (26) 177 (27) 151 (16) 149 (17) 145 (11) 137 (11) 136 (13) 135 (44) 123 (16) 121 (37) 119 (17) 111 (17) 110 (11) 109 (33) 108 (11) 107 (36) 106 (11) 105 (27) 97 (10) 95 (34) 93 (36) 91 (27) 81 (25) 79 (20) 77 (17) 71 (36) 69 (16) 67 (20) 55 (27) 53 (16) 45 (13) 43 (100).59-Methylenedispirodioxolane-2,29-tricyclo5.3.1.13,9dodecane- 89,20-dioxolane 11 The unsaturated diketone 4 (1.40 g 6.8 mmol) ethylene glycol (1.30 g 20.4 mmol) one crystal of toluene-p-sulfonic acid and benzene (50 cm3) were placed in a flask fitted with a Dean and Stark trap and the mixture was heated overnight. After cooling solvent was evaporated and the residue filtered under suction through a short silica gel column washing with 20 diethyl ether in petrol.The solvent was removed under reduced pressure to give the product 11 as an oil (1.61 g 81) nmax(paraffin mull)/cm21 3050m 1630m 1255m 1220m 1100s 1010s 980m 930s 910s 880s 850m 820w 790w 750m; dH(CDCl3) 4.75 (2H s) 4.02–4.76 (8H m) 2.67 (2H dd J 13.40 and 3.95) 2.22–1.16 (12H m); dC(CDCl3) 147.0 116.2 112.4 64.8 63.5 39.3 37.2 35.3 29.5 27.3. Dispirodioxolane-2,29-tricyclo5.3.1.13,9dodecane-89,20- dioxolan-59-one 12 A solution of the unsaturated diketal 11 (0.14 g 0.48 mmol) in dichloromethane (15 cm3) was cooled to 278 8C. A stream of ozonised oxygen was passed through the solution until TLC of an aliquot showed the reaction was complete (1 h). While still at 278 8C dimethyl sulfide (2 cm3) was added the solution was stirred at 0 8C (0.5 h) and then at room temperature (1 h).Solvent was removed under reduced pressure water added and the residue extracted with diethyl ether. The diethyl ether solution was washed with water dried (Na2SO4) and solvent evaporated from the filtrate to give a mixture of solid products which were eluted through a silica column using petrol and increasing amounts of diethyl ether. The pure product 12 was obtained as a white solid using 1 1 petrol–diethyl ether (0.11 g 78) mp 145–148 8C (from diethyl ether) (Found C 65.1; H 7.6. C16H22O5 requires C 65.3; H 7.5); nmax(paraffin mull)/cm21 1680m 1290m 1210m 1130m 1100s 1060s 1010m 960m 940m 920m 880w 840w 790w; dH(CDCl3) 4.02–3.68 (8H m) 3.00–2.81 (2H m) 2.41–1.59 (12H m); dC(CDCl3) 212.1 (C) 111.1 (C) 64.8 (CH2) 63.8 (CH2) 46.7 (CH2) 36.4 (CH) 34.8 (CH) 28.8 (CH2) 27.7 (CH2); m/z (>10) 294 (M1 28) 251 (20) 249 (10) 223 (14) 221 (15) 205 (12) 195 (10) 139 (25) 138 (21) 126 (35) 125 (45) 113 (39) 112 (32) 100 (20) 99 (100) 96 (13) 91 (17) 86 (13) 82 (14) 79 (16) 77 (18) 73 (16) 69 (14) 68 (12) 67 (14) 55 (70) 54 (11) 53 (12) 45 (13) 43 (11) 41 (22).Dispirodioxolane-2,29-tricyclo5.3.1.13,9dodecane-89,20- dioxolane-59-one tosylhydrazone 13 Ketone 12 (0.10 g 0.34 mmol) and tosylhydrazine (0.065 g 0.34 mmol) were dissolved in a minimum of warm ethanol and concentrated hydrochloric acid (1 drop) was added. The mixture was allowed to stir overnight at rt during which time a white solid precipitated. After cooling with ice the solid was filtered washed with a little cold ethanol and then dried in air.13C NMR spectroscopy indicated that the sample of 13 was almost pure (0.15 g 95) mp 179–180 8C (Found C 60.0; H 6.5; N 6.15. C23H30O6N2S requires C 59.7; H 6.5; N 6.1); nmax- (paraffin mull)/cm21 3200m 1595w 1210w 1160s 1130w 1100s 1060m 1030m 970w 940m 920m 900w 850w 830w 800w; dH(CDCl3) 7.26 (1H br s) 7.07 (2H d HAB) 6.48 (2H d HAB) 3.10–2.90 (8H m) 2.87–2.63 (1H m) 2.20–2.05 (1H m) 2.05– 1.88 (1H m) 1.62 (3H s) 1.72–1.12 (11H m); dC(CDCl3) 162.2 143.6 135.6 129.0 128.3 112.1 111.0 64.8 64.7 63.9 63.7 38.4 36.7 36.3 35.0 34.5 33.7 31.5 29.3 23.6 21.6; m/z (>20) 463 (M 1 1)1 43 307 (78) 280 (21) 279 (87) 278 (20) 235 (42) 217 (87) 191 (23) 173 (14) 155 (32) 145 (57) 139 (44) 137 (22) 125 (25) 120 (24) 113 (97) 107 (30) 105 (31) 103 (23) 99 (100) 94 (42) 92 (48) 91 (100) 82 (27) 78 (42) 76 (34) 73 (47) 67 (28) 65 (35) 55 (67) 46 (22).Dispirodioxolane-2,29-tricyclo5.3.1.13,9dodec-4-ene-89,20- dioxolane 14 A suspension of the tosylhydrazone 13 (0.82 g 1.8 mmol) in benzene (40 cm3) was cooled in an ice bath and ethereal methyllithium (1.4 mol dm23; 3.8 cm3 5.4 mmol) was added over 5 min. The mixture was stirred for 4 h at rt during which time the original white suspension became a colourless solution then an orange solution and finally an orange suspension. After this time the reaction was quenched by addition of saturated aqueous NH4Cl (20 cm3). The organic layer was separated and the aqueous layer extracted with diethyl ether. The combined organic layers were washed with water (×3) dried (Na2SO4) and the filtrate evaporated to give a sticky oil which was purified by column chromatography on silica gel eluting with light petroleum and increasing amounts of diethyl ether.The product 14 was obtained using 1 4 diethyl ether–petrol (0.28 g 56) mp 122–124 8C (Found C 68.85; H 8.1. C16H22O4 requires C 69.0; H 8.0); nmax(paraffin mull)/cm21 1670w 1260m 1210s 1100s 1040s 1020s 985s 920s 880m 870m 790m 740s 690m; dH(CDCl3) 5.75–5.57 (1H m) 5.51–5.20 (1H m) 4.01–3.81 (8H m) 2.73–2.60 (2H m) 2.37–1.60 (10H m); dC(CDCl3) 128.9 127.9 112.4 112.2 65.0 64.6 63.9 63.5 38.5 36.6 34.2 33.8 33.5 29.3 29.0 27.8; m/z (>10) 278 (M1 15) 233 (33) 217 (12) 216 (18) 209 (11) 149 (12) 139 (19) 137 (13) 125 (20) 113 (21) 112 (36) 106 (13) 99 (100) 95 (13) 91 (24) 79 (13) 77 (11) 55 (16). Tricyclo5.3.1.13,9dodec-4-ene-2,8-dione 15 Tricyclic diketal 14 (0.12 g 0.43 mmol) was added to a stirred solution of acetone (10 cm3) and hydrochloric acid (2 mol dm23; 5 cm3) then stirred overnight at rt.Acetone was removed by evaporation and the residue extracted with chloroform. The combined extracts were washed successively with water and saturated aqueous NaHCO3 dried (Na2SO4) and the solvent evaporated from the filtrate to give a yellowish solid. This was purified by column chromatography on silica gel eluting with light petroleum and increasing amounts of diethyl ether. The white solid product 15 was obtained using 1 1 diethyl ether– petrol (0.082 g 100) mp 150–155 8C nmax(paraffin mull)/cm21 3010w 1705s 1685m 1260w 1230w 1150w 1120w 1100w 1085w 1070w 1030w 1000m 950w 900w 820w; dH(CDCl3) 5.95–5.75 (1H m) 5.44–5.30 (1H m) 3.41–3.24 (1H m) 3.01– 1.84 (11H m); dC(CDCl3) 217.5 (C) 214.1 (C) 128.9 (CH) 127.5 (CH) 45.1 (CH) 41.8 (CH) 41.5 (two CH) 37.5 (CH2) 35.5 (CH2) 32.9 (CH2) 31.4 (CH2); m/z (>20) 190 (M1 35) 172 (28) 144 (20) 133 (37) 129 (40) 117 (22) 116 (21) 108 (39) 107 (40) 105 (28) 96 (47) 95 (61) 94 (44) 93 (27) 92 (25) 91 (100) 80 (22) 79 (61) 78 (30) 77 (53) 67 (29) 66 (28) 65 (27) 55 (41) 54 (29) 53 (27) 52 (53) 51 (57) 50 (53) 41 (26).2,8-Dimethyltricyclo5.3.1.13,9dodec-4-ene-2-syn,8-syn-diol 16 Unsaturated diketone 15 (0.15 g 0.79 mmol) was dissolved in THF (20 cm3; freshly distilled from LiAlH4) in a flask fitted J. Chem. Soc. Perkin Trans. 1 1997 2945 with a septum and a condenser plus drying tube and stirred under a dry N2 atmosphere.Methyllithium solution in diethyl ether (1.4 mol dm23; 2.1 cm3 2.94 mmol) was added dropwise into the flask at 0 8C using a syringe. The reaction mixture was stirred at room temperature (24 h). Damp diethyl ether was added to the reaction mixture followed by water (5 cm3) and stirring continued for a further 10 min. The two layers were separated the aqueous layer extracted with diethyl ether and the combined organic layers dried (Na2SO4). Evaporation of solvent from the filtrate gave the crude product which was purified by column chromatography on silica gel eluting with light petroleum and increasing amounts of diethyl ether. The product 16 was eluted as a colourless oil using 1 1 diethyl ether–petrol (0.135 g 77); nmax(liquid film)/cm21 3460s 1675w 1280m 1255m 1220w 1130s 1075m 1015m 1000s 970w 940s 910m 895m 850w 780m 740m 710m; dH(CDCl3) 5.85–5.74 (1H m) 5.68–5.57 (1H m) 2.76–2.58 (2H m) 2.36–2.53 (12H m) 1.38 (3H s) 1.36 (3H s); dC(CDCl3) 132.8 128.2 73.6 72.0 41.0 38.2 38.1 37.7 33.9 32.8 31.3 30.8 29.4 29.1.2,5,8-Trimethyltricyclo5.3.1.13,9dodec-4-ene-2-syn,8-syn-diol 17 Unsaturated diol 5 (0.30 g 1.27 mmol) was dissolved in ethyl acetate (10 cm3) and palladium catalyst on charcoal (5 mg) was added. The reaction flask was evacuated filled with hydrogen and stirred at room temperature (24 h). The reaction mixture was filtered through Celite and solvent removed under reduced pressure to give a sticky colourless oil. 13C NMR spectroscopy indicated a mixture of two products was present. This was carefully separated by column chromatography on silica gel eluting with petrol and increasing amounts of diethyl ether.The cyclic ether 18 eluted first (eluent 15 diethyl ether in petrol) as a solid and was followed by the diol 17 (eluent 25 diethyl ether in petrol) as an oil (0.21 g 70) nmax(liquid film)/cm21 3400s 1660w 1285s 1245s 1210m 1120s 1080s 1020s 980s 950m 920s 900m 880s 840w 820m 785w; dH(CDCl3) 5.51 (1H d J 11.5) 2.70–1.50 (14H m) 1.80 (3H br s) 1.38 (3H s) 1.37 (3H s); dC(CDCl3) 139.5 (C) 123.6 (CH) 73.5 (C) 71.9 (C) 41.5 (CH) 38.9 (CH) 38.4 (CH2) 38.2 (CH) 37.8 (CH) 32.6 (CH3) 31.4 (CH2) 30.8 (CH3) 29.7 (CH2) 29.3 (CH2) 28.6 (CH3); m/z (M1 and >10) 236 (M1 8) 107 (16) 105 (12) 95 (17) 93 (18) 91 (17) 81 (13) 79 (15) 77 (14) 71 (24) 69 (10) 67 (18) 55 (26) 53 (13) 43 (100) 41 (32). 2,7,9-Trimethyl-8-oxatetracyclo5.4.1.13,10.05,9tridecan-2-endool 18 During the preparation of diol 17 described above the cyclic ether 18 eluted first (0.09 g 30) mp 128–129 8C (from diethyl ether) (Found C 76.6; H 10.5.C15H24O2 requires C 76.2; H 10.3); nmax(paraffin mull)/cm21 3420m 1245m 1200s 1170w 1110s 1060s 1030m 990w 950s 920m 890m 820m 800w 780w 710m; dH(CDCl3) 2.42–1.33 (15H m) 1.38 (3H s) 1.29 (3H s) 1.21 (3H s); dC(CDCl3) 83.2 (C) 82.5 (C) 72.9 (C) 49.1 (CH2) 42.7 (CH) 41.6 (CH2) 41.4 (CH) 40.1 (CH) 38.3 (CH) 34.1 (CH3) 33.8 (CH2) 33.1 (CH2) 32.8 (CH3) 32.0 (CH2) 30.6 (CH3); m/z (>10) 236 (M1 20) 175 (12) 149 (13) 119 (12) 109 (15) 107 (24) 106 (17) 105 (25) 97 (17) 96 (12) 95 (18) 94 (11) 93 (34) 91 (36) 85 (11) 81 (21) 79 (28) 77 (24) 71 (19) 69 (17) 67 (22) 65 (10) 57 (11) 55 (27) 53 (15) 43 (100) 41 (28).A quantitative yield of 18 was obtained when hydrogenation of 5 using H2 and PtO2 was attempted in ethyl acetate solution with addition of two drops of 70 perchloric acid. 9-Hydroxy-7-methyl-8-oxatetracyclo5.4.1.13,10.05,9tridecan-2- one 20 Diester 3 (1.00 g 3.12 mmol) was heated under reflux with acetic acid (8.7 cm3) and hydrochloric acid (5 mol dm23; 5.8 cm3) with stirring for 16 h. The reaction mixture was evaporated to dryness under reduced pressure to give a brown waxy solid. A small amount of water was added and then organic material extracted with chloroform. The combined extracts were washed with saturated aqueous sodium carbonate dried (Na2SO4) and solvent evaporated from the filtrate to leave a solid product. This crude solid was recrystallised from diethyl ether to give clean hemiketal 20 (0.62 g 90) mp 132–134 8C (Found C 70.1; H 8.2.C13H18O3 requires C 70.2; H 8.2); nmax(paraffin mull)/cm21 3410s 1690s 1250m 1230m 1170m 1140w 1120s 1100s 1080s 1070s 1015s 990s 980m 960m 940s 915s 885w 855m 840m 785w 750s 695w 680w 660m; dH(CDCl3) 3.69 (1H s) 2.77–1.68 (14H m) 1.24 (3H s); dC(CDCl3) 220.5 (C) 106.4 (C) 82.4 (C) 48.4 (CH2) 46.0 (CH2) 45.5 (CH) 44.8 (CH) 43.5 (CH) 42.4 (CH) 38.7 (CH2) 33.4 (CH2) 33.2 (CH2) 29.7 (CH3); m/z (>20) 222 (M1 25) 204 (25) 194 (24) 179 (23) 176 (24) 161 (26) 138 (25) 135 (22) 133 (23) 121 (23) 110 (24) 109 (55) 108 (36) 107 (47) 105 (30) 97 (31) 96 (57) 95 (100) 94 (43) 93 (51) 91 (74) 83 (23) 82 (29) 81 (71) 80 (25) 79 (84) 77 (69) 69 (34) 68 (26) 67 (57) 65 (29) 55 (95) 53 (36) 43 (45) 41 (30).2,9-Dimethyl-8-oxatetracyclo5.4.1.13,10.05,9tridecane-2-endo,7- diol 22 A solution of the unsaturated diol 5 (0.10 g 0.34 mmol) in dichloromethane (15 cm23) was cooled to 278 8C. A stream of ozonised oxygen was passed through the solution for 30 min. While still at 278 8C dimethyl sulfide (1 cm3) was added the solution was then stirred at 0 8C (0.5 h) and at rt (1 h). Solvent was evaporated under reduced pressure water was added then the residue extracted with diethyl ether. The extract was then washed with water dried (Na2SO4) and solvent evaporated from the filtrate to give a solid product which was purified by column chromatography on silica gel using light petroleum and increasing amounts of diethyl ether. The pure product 22 was eluted with 1 1 diethyl ether–petrol (0.08 g 80) mp 144–145 8C (from 1 1 diethyl ether–petrol) (Found C 70.9; H 9.5.C14H22O3 requires C 70.6; H 9.3); nmax(paraffin mull)/cm21 3440–3120m (br) 1150m 1120m 1070m 1020m 1000w 980m 960m 935m 910m 850w 820w; dH(CDCl3) 2.51–1.48 (15H m) 1.43 (3H s) 1.37 (3H s) 1.29–1.19 (1H m); dC(CDCl3) 106.9 80.7 72.6 48.1 41.1 (two peaks) 39.8 39.1 38.0 34.1 33.5 32.8 32.7 31.6; m/z (significant peaks plus >10) 238 (M1 2) 223 (7) 220 (6) 205 (7) 179 (10) 177 (12) 161 (15) 160 (17) 159 (13) 150 (15) 149 (13) 145 (15) 137 (12) 136 (12) 135 (25) 133 (24) 123 (18) 122 (63) 121 (25) 120 (22) 119 (36) 118 (10) 114 (12) 111 (17) 110 (13) 109 (30) 108 (17) 107 (75) 106 (68) 105 (60) 97 (11) 95 (28) 94 (18) 93 (51) 92 (16) 91 (44) 85 (15) 83 (11) 81 (29) 79 (34) 77 (26) 71 (36) 70 (10) 69 (21) 67 (23) 65 (10) 55 (32) 53 (15) 43 (100) 41 (36).7-Hydroxymethyl-2,9-dimethyl-8-oxatetracyclo5.4.1.13,10.05,9- tridecane-2-endo-ol 24 A solution of m-chloroperbenzoic acid (MCPBA; 0.16 g 80– 85 purity ca. 0.76 mmol) in dichloromethane (5 cm3) was added dropwise to a vigorously stirred mixture of the unsaturated diol 5 (0.18 g 0.75 mmol) and aqueous sodium hydrogen carbonate (0.5 mol dm23; 1.1 cm3). The reaction mixture was stirred at rt for 4 h then saturated aqueous sodium sulfide (1.5 cm3) was added to destroy the remaining peracid. The organic layer was separated and the aqueous layer extracted with dichloromethane. The combined extracts were washed with water and dried (Na2SO4). After evaporation of solvent from the filtrate a white sticky oil was obtained which crystallised on addition of diethyl ether giving 24 (0.15 g 89) mp 135– 138 8C (Found C 71.1; H 9.3.C15H24O3 requires C 71.4; H 9.6); nmax(paraffin mull)/cm21 3380s 1260m 1215w 1145m 1130m 1085s 1075s 1060s 1020m 1000w 960m 940m 920m 900m 840m 815w 775w; dH(CDCl3) 3.45–3.38 (1H m) 3.34– 3.25 (1H m) 2.50–2.37 (1H m) 2.31–2.12 (5H m) 2.00–1.67 (6H m) 1.65–1.42 (4H m) 1.40 (3H s) 1.29 (3H s); dC(CDCl3) 85.6 83.1 72.7 68.3 42.3 42.2 41.2 40.0 38.4 36.4 34.3 33.9 33.0 32.3 32.1; m/z (significant peaks plus 2946 J. Chem. Soc. Perkin Trans. 1 1997 >10) (252 M1 not observed) 237 (M 2 15)1 4 234 (M 2 18)1 13 161 (14) 147 (18) 146 (13) 135 (11) 133 (20) 132 (12) 121 (16) 120 (10) 119 (26) 111 (10) 109 (18) 107 (33) 106 (18) 105 (37) 97 (15) 95 (28) 94 (10) 93 (32) 91 (34) 83 (18) 81 (26) 79 (30) 77 (24) 71 (26) 69 (45) 67 (26) 57 (23) 55 (45) 53 (17) 44 (18) 43 (100) 41 (46).Determination of the crystal structures of 5 7 and 10 Crystals of diols 5 and 7 were grown from diethyl ether solution and diol 10 from ethyl acetate. There was no indication of guest inclusion by IR and 1H NMR spectroscopy or by microanalysis in any case. Data for all three structures were recorded using an Enraf-Nonius CAD4 X-ray diffractrometer in q–2q scan mode using nickel filtered copper radiation (l 1.5418 Å). Data collection and processing procedures have been described.26 Corrections were made for absorption 27 and for any crystal decomposition. For 5 and 10 the structures were determined by direct phasing (MULTAN28) and Fourier methods. The positions of the hydroxy hydrogen atoms were determined from difference Fourier maps.All other hydrogen atoms were included in calculated positions. The positions of the hydroxy hydrogen atoms were refined and all hydrogen atoms were assigned thermal parameters equal to those of the atom to which they were bonded. Positional and anisotropic thermal parameters for the non-hydrogen atoms were refined using full matrix least squares.29 The final residuals were 0.051 and 0.077 and the largest peaks in the final difference maps were 0.26 and 0.27 e Å23 for 5 and 10 respectively. For 7 the initial positional parameters for the diol were taken from a previously determined structure of the non-methylated diol 25 22 since the two structures were clearly isomorphous. A difference Fourier synthesis revealed the additional methyl carbon position.The structure was refined anisotropically.30 The hydroxy hydrogen position was taken from a difference Fourier and its position was refined. Methyl and methylene hydrogen atoms were included in calculated positions with isotropic temperature factors set equal to those of the atoms to which they were bonded. However it was clear from a difference map that the hydrogen atoms of the C(6) methyl group were disordered. Two different sets of hydrogen atom positions were included with equal occupancy. The final residual was 0.037. The R factor for the other enantiomer was the same. The largest peak in the final difference map was 0.25 e Å23. Reflection weights used for all three structure refinements were 1/s2(Fo) with s(Fo) being derived from s(Io) = s2(Io) 1 (0.04Io)2� �� . The weighted residual was defined as Rw = (SwD2/SwFo 2)� �� .Atomic scattering factors and anomalous dispersion parameters were from International Tables for X-ray Crystallography.31 ORTEP-II32 running on a Macintosh IIcx was used for the structural diagrams and a DEC Alpha AXP workstation was used for calculations. In previous analyses of diols 2513,22 and 26 23 we have observed that the central atom C(8) of the propano bridge was disordered as required by space group symmetry. This uncertainty in the position of C(8) which is indicated by the higher standard deviation associated with it is reflected by an inequality and/or a shortening of the C(7)–C(8) and C(7)9–C(8) bond distances together with an increase in the bridge angles from the tetrahedral value. There is again evidence for this phenomenon in 7 (where space group symmetry requires disorder) and in 10.In these structures the bridge angle values are larger and the bridge bond length values shorter than expected. Atomic coordinates thermal parameters and bond lengths and angles have been deposited at the Cambridge Crystallographic Data Centre (CCDC). See Instructions for Authors 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 207/128. Acknowledgements We thank the Australian Research Council for financial support of this work. References 1 R. Bishop ‘Helical Host Lattices Formed by Alicyclic Diols’ in Comprehensive Supramolecular Chemistry eds. J. L. Atwood J. E. D. Davies D. D. MacNicol and F. Vögtle vol.6 Solid-state Supramolecular Chemistry Crystal Engineering eds. D. D. MacNicol F. Toda and R. Bishop Pergamon Oxford 19985–115. 2 R. Bishop I. G. Dance S. C. Hawkins and M. L. Scudder J. Inclusion Phenom. 1987 5 229. 3 R. Bishop D. C. Craig M. L. Scudder A. P. Marchand and Z. Liu J. Chem. Soc. Perkin Trans. 2 1995 1295. 4 W. Parker R. L. Tranter C. I. F. Watt L. W. K. Chang and P. v. R. Schleyer J. Am. Chem. Soc. 1974 96 7121. 5 T. S. Sorensen and S. M. Whitworth J. Am. Chem. Soc. 1990 112 8135. 6 K. Schulze G. Winkler W. Dietrich and M. Mühlstädt J. Prakt. Chem. 1977 319 463. 7 R. W. Alder D. D. Ellis A. G. Orpen and P. N. Taylor Chem. Commun. 1996 539. 8 T. Sasaki S. Eguchi T. Toru and K. Itoh J. Am. Chem. Soc. 1972 94 1357. 9 T. Sasaki S. Eguchi and M. Mizutani Tetrahedron Lett.1975 2685. 10 H. D. Ward and R. K. Murray Jr. J. Org. Chem. 1990 55 81. 11 H. Meerwein F. Kiel G. Klösgen and E. Schoch J. Prakt. Chem. 1922 104 161. 12 S. C. Hawkins PhD Thesis University of New South Wales 1986. 13 A. T. Ung R. Bishop D. C. Craig I. G. Dance A. D. Rae and M. L. Scudder J. Inclusion Phenom. 1993 15 385. 14 A. Mooradian and J. B. Cloke J. Am. Chem. Soc. 1945 67 942. 15 T. W. Bell H.-J. Choi and W. Harte J. Am. Chem. Soc. 1986 108 7427. 16 D. Y. Chang C.-F. Yam S.-Y. Chan S. H. Lee and H.-C. Lee J. Org. Chem. 1966 31 3297. 17 D. Y. Chang S. H. Lee and H.-C. Lee J. Org. Chem. 1967 32 3716. 18 E. V. Dehmlow and S. Barahona-Naranjo J. Chem. Res. (S) 1981 142. 19 M. A. Viswamitra R. Radhakrishnan J. Bandekar and G. R. Desiraju J. Am. Chem. Soc. 1993 115 4868.20 H. S. Rzepa M. H. Smith and M. L. Webb J. Chem. Soc. Perkin Trans. 2 1994 703. 21 CUSCIC L. Quijano J. S. Calderon G. F. Gomez P. J. Lopez T. Rios and F. R. Fronczek Phytochem. 1984 23 1971; POITDL W. Fenical G. R. Schulte J. Finer and J. Clardy J. Org. Chem. 1978 43 3628; PILCES V. Cody and J. R. Luft J. Mol. Struct. 1994 317 89. 22 I. G. Dance R. Bishop S. C. Hawkins T. Lipari M. L. Scudder and D. C. Craig J. Chem. Soc. Perkin Trans. 2 1986 1299; I. G. Dance R. Bishop and M. L. Scudder J. Chem. Soc. Perkin Trans. 2 1986 1309. 23 S. C. Hawkins R. Bishop D. C. Craig I. G. Dance A. D. Rae and M. L. Scudder J. Chem. Soc. Perkin Trans. 2 1993 1737. 24 R. Bishop S. Choudhury and I. Dance J. Chem. Soc. Perkin Trans. 2 1982 1159. 25 R. Bishop D. C. Craig I. G. Dance S. Kim M.A. I. Mallick K. C. Pich and M. L. Scudder Supramol. Chem. 1993 1 171. 26 R. M. H. Banda I. G. Dance T. D. Bailey D. C. Craig and M. L. Scudder Inorg. Chem. 1989 28 1862. 27 J. de Meulenaer and H. Tompa Acta Crystallogr. 1965 19 1014. 28 P. Main S. J. Fiske S. E. Hull L. Lessinger G. Germain J.-P. Declercq and M. M. Woolfson ‘MULTAN80 A System of Computer Programs for the Automatic Solution of Crystal Structures from X-ray Diffraction Data’ Universities of York England and Louvain Belgium 1980. 29 W. R. Busing K. O. Martin and H. A. Levy ORFLS Report ORNL-TM-305 Oak Ridge National Laboratory TN USA 1962. 30 A. D. Rae ‘RAELS. A Comprehensive Constrained Least Squares Refinement Program’ University of New South Wales 1989. 31 International Tables for X-Ray Crystallography eds. J. A. Ibers and W.C. Hamilton vol. 4 Kynoch Press Birmingham 1974. 32 C. K. Johnson ORTEP-II Oak Ridge National Laboratory TN USA 1976. Paper 6/07710B Received 13th November 1996 Accepted 8th May 1997 © Copyright 1997 by the Royal Society of Chemistry J. Chem. Soc. Perkin Trans. 1 1997 2937 Simple synthetic entries into the tricyclo5.3.1.13,9dodecane and 8-oxatetracyclo5.4.1.13,10.05,9tridecane ring systems Weimin Yue Roger Bishop,* Marcia L. Scudder and Donald C. Craig School of Chemistry The University of New South Wales Sydney 2052 Australia The bis(enolate) of diester 1 undergoes a double intramolecular alkylation reaction with 3-chloro-2- chloromethylprop-1-ene 2 to form the tricyclic product 3 in 75 yield. This conversion represents the first high-yielding route to derivatives of tricyclo5.3.1.13,9dodecane an alicyclic ring system of considerable theoretical and structural interest.Diol derivatives 5 7 10 16 and 17 are prepared to investigate further the crystal engineering requirements for obtaining new helical tubuland hosts. The X-ray structures of 5 10 and 7 reveal one- two- and three-dimensional hydrogen bonded lattice structures respectively despite their remarkable molecular similarity. Solid 5 comprises chains assembled through intermolecular ? ? ?HO? ? ?HO? ? ?HO? ? ? and novel intramolecular alkene ? ? ?HO hydrogen bonds; while diol 10 forms double layers of diols constructed from recurved spiral chains (four molecules per repeat unit) of intermolecular ? ? ?HO? ? ?HO? ? ?HO? ? ? hydrogen bonds. When crystallised from diethyl ether the hydroxy groups of 7 are linked ? ? ?HO? ? ?HO? ? ?HO? ? ? around threefold screw axes to give a further example of the helical tubuland lattice.This is a microporous solid with empty tubes of cross-sectional area 17.8 Å2 parallel to z. Appropriately functionalised tricyclo5.3.1.13,9dodecanes undergo efficient intramolecular cyclisation providing compounds 18 20 22 and 24 which are the first reported derivatives of 8-oxatetracyclo5.4.1.13,10.05,9tridecane. Introduction During the course of our continuing studies into the helical tubuland family of diol inclusion hosts 1 we required a convenient preparation of 2,5,8-trisubstituted tricyclo5.3.1.13,9- dodecane derivatives in order to investigate compounds such as 5 7 10 16 and 17. The closely related molecular structures of these diols fit the formal molecular rules required for potential helical tubuland lattice formation 2,3 and therefore were important target molecules.Relatively little work had been reported previously on syntheses of this alicyclic skeleton and none which could supply the necessary functionality at these three positions. This paper provides a simple solution to this problem and also describes the first derivatives of the previously unknown 8-oxatetracyclo5.4.1.13,10.05,9tridecane system. Results and discussion Synthetic entry to 2,5,8-trisubstituted tricyclo5.3.1.13,9- dodecanes Few synthetic data on tricyclo5.3.1.13,9dodecane (1,1-bishomoadamantane) derivatives have been published despite this ring system being of considerable interest from a theoretical viewpoint.Parker et al. 4 have predicted enhanced reactivity due to relief of angle strain at positions C3 and C7 in reactions leading to bridgehead carbocation or radical formation. Similarly the formation of bridgehead alkene derivatives is expected to be particularly favourable. Even the possible formation of bridgehead inside-pyramidalised hydrogen structures has been mooted.5 The 1,1-bishomoadamantane skeleton is therefore quite different in its behaviour to simpler homologues such as adamantane. These properties which are reflected in the difficulty of its synthesis arise because part of its skeleton comprises a bicyclo- 3.3.3undecane (manxane) sub-structure where flattening of the bridgehead sites creates significant strain.4 Hence preparative methods involving formation of the required eightmembered rings by closure methods are rarely effective although syntheses of double bridgehead 1,5-diaza- and 1,5- diphospha-manxanes have been most successful.6,7 The following approaches to the 1,1-bishomoadamantane skeleton have been reported.Adamantanone may be ring expanded easily into homoadamantan-4-one and this in turn subjected to Tiffeneau–Demjanov ring expansion which produced tricyclo5.3.1.13,9dodecan-4-one (15 yield). From this material Sasaki and co-workers were able to prepare several other 4-substituted derivatives and also the parent hydrocarbon but attempts to obtain the ring system through ring expansion of 3-tosyloxymethylhomoadamantane were unsuccessful.8 In an alternative approach Ag I-assisted hydrolysis of the dichlorocarbene adduct of homoadamant-4-ene gave a mixture of products including 5-chlorotricyclo5.3.1.13,9dodec-5-en-4- ol (30).9 Ward and Murray 10 used the route to tricyclo5.3.1.13,9- dodecan-4-one outlined above to prepare several bridgehead enolate derivatives and ultimately the bridgehead alkene itself in accord with the above ideas of favoured sp2 carbon hybridisation at this