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Facile Synthesis of Diastereoisomerically and Optically Pure 2‐Substituted Hexahydro‐1 H ‐pyrrolizin‐3‐ones
Author(s) -
Siegrist Romain,
Baumgartner Corinne,
Seiler Paul,
Diederich François
Publication year - 2005
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200590158
Subject(s) - chemistry , diastereomer , ylide , intramolecular force , aldehyde , wittig reaction , proline , optically active , catalysis , stereochemistry , cleavage (geology) , absolute configuration , proton nmr , organic chemistry , amino acid , biochemistry , geotechnical engineering , fracture (geology) , engineering
We report a short synthetic route that provides optically active 2‐substituted hexahydro‐1 H ‐pyrrolizin‐3‐ones in four steps from commercially available Boc ( tert ‐but(oxy)carbonyl))‐protected proline. Diastereoisomers (−)‐ 11 and (−)‐ 12 were assembled from the proline‐derived aldehyde (−)‐ 8 and ylide 9 via a Wittig reaction and subsequent catalytic hydrogenation ( Scheme 3 ). Cleavage of the Boc protecting group under acidic conditions, followed by intramolecular cyclization, afforded the desired hexahydro‐1 H ‐pyrrolizinones (−)‐ 1 and (+)‐ 13 . Applying the same protocol to ylide 19 afforded hexahydro‐1 H ‐pyrrolizinones (−)‐ 25 and (−)‐ 26 ( Scheme 5 ). The absolute configuration of the target compounds was determined by a combination of NMR studies ( Figs. 1 and 2 ) and X‐ray crystallographic analysis ( Fig. 3 ).