1-Magnesiotetrahydroisoquinolyloxazolines as Chiral Nucleophiles in Stereoselective Additions to Aldehydes: Auxiliary Optimization, Asymmetric Synthesis of (+)-Corlumine, (+)-Bicuculline, (+)-Egenine, and (+)-Corytensine, and Preliminary (13)C NMR Studies of 1-Lithio- and 1-Magnesiotetrahydroisoquinolyloxazolines

Robert E. Gawley; Pingsheng Zhang

doi:10.1021/jo961164u

1-Magnesiotetrahydroisoquinolyloxazolines as Chiral Nucleophiles in Stereoselective Additions to Aldehydes: Auxiliary Optimization, Asymmetric Synthesis of (+)-Corlumine, (+)-Bicuculline, (+)-Egenine, and (+)-Corytensine, and Preliminary (13)C NMR Studies of 1-Lithio- and 1-Magnesiotetrahydroisoquinolyloxazolines

J Org Chem. 1996 Nov 15;61(23):8103-8112. doi: 10.1021/jo961164u.

Authors

Robert E. Gawley¹, Pingsheng Zhang

Affiliation

¹ Department of Chemistry, University of Miami, Coral Gables, Florida 33124-0431.

PMID: 11667797
DOI: 10.1021/jo961164u

Abstract

Transmetalation of 1-lithiotetrahydroisoquinolyloxazolines with magnesium halides affords Grignard reagents that add to aldehydes with up to 80% selectivity for one of the four possible diastereomeric products. An oxazoline chiral auxiliary derived from camphor provides an optimal blend of diastereoselectivity and isomer separability. Synthetic applications of the optimal auxiliary, patterned after a literature approach in the racemic series, comprise an improved (formal) synthesis of bicuculline, egenine, and corytensine, as well as an efficient synthesis of corlumine. Preliminary NMR studies show that both 1-lithio- and 1-magnesiotetrahydroisoquinolyloxazolines are dynamic mixtures in THF solution at low temperatures. The barrier to pyramidal inversion of the secondary Grignard reagent is in the 9.8-10.1 kcal/mol range, while an upper limit of about 8.2 kcal/mol can be assigned to the barrier to the organolithium inversion.