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Enantioselective Synthesis of (–)‐Methoxyestrone
Author(s) -
Betík Robert,
Kotora Martin
Publication year - 2011
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.201100317
Subject(s) - enantioselective synthesis , chemistry , ketone , aldehyde , stereochemistry , conjugate , bicyclic molecule , imine , enone , side chain , addition reaction , organic chemistry , catalysis , mathematical analysis , polymer , mathematics
Enantioselective synthesis of unnatural (–)‐methoxyestrone in 12 steps from the commercially available tetralone based on the formation of a chiral bicyclic intermediate having the A–B steroid ring framework was accomplished. The crucial synthetic step comprised the enantioselective conjugate addition of vinylmagnesium bromide to a chiral imine formed from a trisubstituted cyclic α,β‐unsaturated aldehyde with >98 % ee , giving rise to the stereoselectively substituted building block possessing the A–B steroid rings. Further steps included the construction of the side chain containing the triple bond, and the obtained enyne was subjected to a Pauson–Khand reaction that furnished stereoselectively an intermediate tetracyclic ketone. Further functional group transformations yielded the target compound.