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

TY - JOUR

T1 - Nonracemic, chiral homoenolate reagents derived from (cycloalk-1-enyl)methyl carbamates and evaluation of their configurational stabilities

AU - Özlügedik, M.

AU - Kristensen, Jesper Langgaard

AU - Wibbeling, B.

AU - Fröhlich, R.

AU - Hoppe, D.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0036169729&partnerID=8YFLogxK

M3 - Journal article

AN - SCOPUS:0036169729

SN - 1434-193X

SP - 414

EP - 427

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 3

ER -