Meso-Epoxide ring opening desymmetrization

To avoid the inherent limitations of a kinetic resolution process, the reaction was extended to desymmetrization of prochiral meso epoxides. A number of cyclic di-methylidene epoxides were synthesized and subjected to treatment with Et2Zn in the presence of Cu(OTf)2 and ligands 42 or 43. As in the case mentioned above, ligand 42 was superior in terms of selectivity. Cydohexane derivative 46 gave the ring-opened product with a 97% ee and in a 90% isolated yield, with a y/a ratio of 98 2 (Scheme 8.28). The other substrates investigated produced sigmficantly lower ees of between 66% and 85%. 

Nugent, W. A. (1998) Desymmetrization of meso-epoxides with halides A new catalytic reaction based on mechanistic insight, J. Am. Chem. Soc., 120 7139-7140. Bruns, S. Haufe, G. (1999) Catalytic asymmetric ring opening of epoxides to chlorohydrins with mild chloride donors and enantiopure titanium complexes.. 

The desymmetrization of meso-e poxides such as cyclohexene epoxide (55, Scheme 13.27) has been achieved both by enantioselective isomerization, e.g. to allylic alcohols (56, path A, Scheme 13.27) or by enantiotopos-differentiating opening by nucleophiles, affording trans-/ -substituted alcohols and derivatives (57, path B, Scheme 13.27). As indicated in Scheme 13.27, the allylic alcohols 56 can also be prepared from the ring-opening products 57 by subsequent elimination of the nucleophile. 

Highly enantioselective catalytic desymmetrization of meso-epoxides through nucleophihc ring opening was first effectively demonstrated by Nugent, who found that a zirconium trialkanolamine complex catalyzed the addition of azi-dosilanes to meso-epoxides (Scheme 1) [3]. Azide has been the most widely explored nitrogen nucleophile [4,5,6,7], in part due to its utiHty as an amine sur-... 

Desymmetrization of meso epoxides by ring-opening reaction using thiol as nucleophile catalyzed by chiral salen-Ti Lewis acid was first reported by Hou [238]. Under the optimized conditions, the reaction of meso epoxides in the presence of 5 mol% of catalyst gave the corresponding -hydroxy sulfide compounds in good yields (86-93%) with moderate enantiomeric excesses (46-63%) (Scheme 14.101). The use of BINOL-Ti or salen-Ti catalyst for the same type of reaction afforded the corresponding chiral P-hydroxysulfides in moderate yield and enantiomeric excess values (<73%) [239]. 

There is significant interest in controlling the absolute stereochemistry of ring opening in epoxide/C02 copolymerization. Cyciohexene oxide, a meso molecule, is an ideal substrate for desymmetrization using chiral catalysts. In 1999, Nozaki et al7 reported that a 1 1 mixture of ZnEt2 and (S)-diphenyl (pyrrolidine-2-yl)methanol (11) (Scheme 13) was active for stereoselective cyciohexene oxide/C02 copolymerization at 40 °C and 30 atm. CO2 (Scheme 14). The resultant polycarbonate contained 100% carbonate linkages, had an Ain of... 

Aluminum alkoxide can be also used as a base. Chiral aluminum alkoxide prepared from Al(Oi-Pr)3 and BINOL mediated asymmetric desymmetrization of meso-cyclopentenone epoxide through p-eliminative ring-opening reaction to give hydroxylated cyclopentenone in 95% ee (Scheme 6.77) [97]. 

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