"Asymmetric anionic cyclization of achiral olefinic organolithiums" by Michael James Mealy

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. ^

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