Nonracemic, chiral homoenolate reagents derived from (cycloalk-1-enyl)methyl carbamates and evaluation of their configurational stabilities

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M. Özlügedik, Jesper Langgaard Kristensen, B. Wibbeling, R. Fröhlich, D. Hoppe

Several (cycloalk-1-enyl)methyl N,N-diisopropylcarbamates 11 were synthesised by three different methods and their asymmetric deprotonation by butyllithium/(-)-sparteine was investigated. The ratios of epimeric ion pairs 18·4/epi-18·4 were determined by (stereospecific) trimethylsilylation, forming the products 19/ent-19. Lithiated 2-unsubstituted (cyclopent-1-enyl) methyl carbamates, such as 11a or 11h, epimerise rapidly at -78 °C and the thermodynamically controlled ratio is opposite to the kinetically achieved ratio. High configurational stability was found for the 2-methylcycloalk-1-enyl derivatives 11d, 11e and 11j. These turned out to be valuable reagents for enantioselective homoaldol reaction; er values of up to 96:4 could be achieved. X-ray crystal structure analyses with anomalous diffraction, obtained from the heavy atom containing products 22, 23b, 27d, and 27e derived from (2-methylcyclopentenyl)methyl and (2-methyl-cyclohexenyl)methyl reagents, established the (1S) configuration of the major lithium compound. Thus, the kinetically controlled deprotonation of the corresponding allyl carbamates removes the (pro-S) proton. Overall, a simple method for the enantioselective synthesis of cyclic homoaldol adducts from achiral precursors is reported.
Original languageEnglish
JournalEuropean Journal of Organic Chemistry
Issue number3
Pages (from-to)414-427
Number of pages14
ISSN1434-193X
Publication statusPublished - 1 Jan 2002

ID: 45437991