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Phosphine‐Catalyzed (4+1) Annulation: Rearrangement of Allenylic Carbamates to 3‐Pyrrolines through Phosphonium Diene Intermediates
Author(s) -
Blank Brian R.,
Andrews Ian P.,
Kwon Ohyun
Publication year - 2020
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.202000626
Subject(s) - phosphonium , phosphine , chemistry , annulation , diene , cope rearrangement , catalysis , combinatorial chemistry , organic chemistry , cyclopentene , allene , medicinal chemistry , natural rubber
We have developed a phosphine‐catalyzed (4+1) annulative rearrangement for the preparation of 3‐pyrrolines from allenylic carbamates via phosphonium diene intermediates. We employed this methodology to synthesize an array of 1,3‐disubstituted‐ and 1,2,3‐trisubstituted‐3‐pyrrolines, including the often difficult to prepare 2‐alkyl variants. A mechanistic investigation employing allenylic acetates and mononucleophiles unexpectedly unveiled that a phosphine‐catalyzed (4+1) reaction for the construction of cyclopentene products, previously reported by Tong, might not occur through a phosphonium diene, as had been proposed, but rather through multiple mechanisms working in concert. Consequently, our phosphine‐catalyzed rearrangement is most likely the first transformation to involve the unequivocal formation of a phosphonium diene intermediate along the reaction pathway. To demonstrate the synthetic utility of this newly developed reaction, we have completed concise formal syntheses of the pyrrolizidine alkaloids (±)‐trachelanthamidine and (±)‐supinidine.