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A novel enantioselective synthesis of (S)‐(−)‐ and (R)‐(+)‐nornicotine via alkylation of a chiral 2‐hydroxy‐3‐pinanone ketimine template
Author(s) -
Swango Jason H.,
Bhatti Balwinder S.,
Qureshi Muhammad M.,
Crooks Peter A.
Publication year - 1999
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1999)11:4<316::aid-chir9>3.0.co;2-d
Subject(s) - chemistry , nornicotine , alkylation , enantioselective synthesis , stereochemistry , chirality (physics) , pyridine , intramolecular force , enantiomer , alkaloid , catalysis , medicinal chemistry , organic chemistry , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
An asymmetric synthesis of the optically pure isomers of the minor tobacco alkaloid and CNS nicotine metabolite, nornicotine, has been achieved with moderately high optical purity. The synthetic pathway involves alkylation of a chiral ketimine, prepared from either 1R,2R,5R‐(+)‐ or 1S,2S,5S‐(−)‐2‐hydroxy‐3‐pinanone and 3‐(aminomethyl)pyridine with 3‐bromopropan‐1‐ol. After cleavage of the respective C‐alkylated ketimines with NH 2 OH·HCl, and treatment of the resulting amino alcohols with HBr, followed by base‐catalyzed intramolecular ring closure, (S)‐(−)‐nornicotine and (R)‐(+)‐nornicotine were obtained with ee values of 91% and 81%, respectively. Chirality 11:316–318, 1999. © 1999 Wiley‐Liss, Inc.