Title

Asymmetric anionic cyclization of achiral olefinic organolithiums

Date of Completion

January 2002

Keywords

Chemistry, Organic

Degree

Ph.D.

Abstract

The asymmetric cyclization of achiral olefinic organolithiums in the presence of a chiral ligand has been explored. Investigations into the scope of the reaction indicate that, in the presence of the chiral lupine alkaloid, (−)-sparteine, the cyclization of achiral primary-, vinyl-, and aryllithiums containing a remote carbon-carbon π-bond may proceed enantioselectively. For instance, the organolithium derived from N,N-diallyl-2-bromoaniline by low-temperature lithium-bromine exchange cyclizes in the presence of (−)-sparteine with a high degree of enantioselectivity. The resulting [(3-indolinyl)methyl]lithium may be readily functionalized by addition of an electrophile to give a 3-substituted indoline with enantiomeric excess approaching 90%. The effect of experimental variables on the enantioselectivity of this process has been examined. ^ The (−)-sparteine-mediated cyclization of the organolithium derived from N,N-diallyl-2-bromoaniline provides convenient access to 3-methylindolines of (R)-absolute configuration. The utility of this process is limited by the availability of only the (−)-antipode of sparteine. In an effort to circumvent this problem, the efficacy of a number of chiral diamine, amino-ether, and diether ligands has been explored. The effect of 25 ligands and their architectural significance in this chemistry is discussed. ^ In addition, the use of anionic and radical cyclization for the diastereoselective ring construction of 1,3-disubstituted indans has been explored. The cyclization of the organolithium derived from 2-(2-iodo-1-methylethyl)styrene was found to deliver cis-1,3-disubstituted indans in >85% diastereomeric excess. ^