Phosphine‐Catalyzed (4+1) Annulation: Rearrangement of Allenylic Carbamates to 3‐Pyrrolines through Phosphonium Diene Intermediates

• Published in: ChemCatChem Vol. 12; no. 17; pp. 4352 - 4372
• Main Authors: Blank, Brian R., Andrews, Ian P., Kwon, Ohyun
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 04.09.2020
• Subjects: (4+1) annulation; 3-pyrroline; Acetates; Alkaloids; Carbamates (tradename); Chemical reactions; Cyclopentene; phosphine catalysis; Phosphines; phosphonium diene; pyrrolizidine alkaloid; phosphonium diene; pyrrolizidine alkaloid; 3-pyrroline; phosphine catalysis; (4+1) annulation
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.202000626

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. From allenes to pyrrolizidines: A phosphine‐catalyzed (4+1) annulative rearrangement of allenylic carbamates yields 1,3‐disubstituted‐ and 1,2,3‐trisubstituted‐3‐pyrrolines, including difficult to prepare 2‐alkyl variants, via phosphonium diene intermediates. This new methodology has been employed as the key step in concise formal syntheses of the pyrrolizidine alkaloids (±)‐trachelanthamidine and (±)‐supinidine.