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Sequential Mannich‐Aza‐Michael Reactions for the Stereodivergent Synthesis of Highly Substituted Pyrrolidines
Author(s) -
Enkisch Charlotte,
Schneider Christoph
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900787
Subject(s) - diastereomer , chemistry , michael reaction , intramolecular force , mannich reaction , mannich base , protecting group , sequence (biology) , side chain , stereochemistry , combinatorial chemistry , organic chemistry , catalysis , polymer , biochemistry , alkyl
A stereodivergent synthesis of 2,3,5‐trisubstituted pyrrolidines by an organocatalytic Mannich/aza‐Michael addition sequence has been developed. Depending upon the choice of the base used in the intramolecular aza‐Michael additions, 2,5‐ trans ‐ or 2,5‐ cis ‐configured pyrrolidines were obtained in high yields and excellent diastereomeric ratios. Selective deprotection of the amino group and the side‐chain hydroxy group proceeded without loss of diastereomeric purity. The stereodivergent outcome of the key aza‐Michael reactions is the result of thermodynamically versus kinetically controlled cyclization.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)