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Bis(oxazoline) Lewis Acid Catalyzed Aldol Reactions of Pyridine N ‐Oxide Aldehydes—Synthesis of Optically Active 2‐(1‐Hydroxyalkyl)pyridine Derivatives: Development, Scope, and Total Synthesis of an Indolizine Alkaloid
Author(s) -
Landa Aitor,
Minkkilä Anna,
Blay Gonzalo,
Jørgensen Karl Anker
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200501475
Subject(s) - chemistry , pyridine , indolizine , aldol reaction , oxazoline , pyridine n oxide , enantioselective synthesis , racemization , optically active , total synthesis , organic chemistry , enantiomeric excess , lewis acids and bases , catalysis , combinatorial chemistry
A new, short, and simplified procedure for the synthesis of optically active pyridine derivatives from pro‐chiral pyridine‐ N ‐oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and 1‐oxypyridine‐2‐carbaldehyde derivatives catalyzed by chiral copper( II )–bis(oxazoline) complexes gave optically active 2‐(hydroxyalkyl)‐ and 2‐( anti ‐1,2‐dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities—up to 99 % enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.