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. 2020 Sep 4;12(17):4352-4372.
doi: 10.1002/cctc.202000626. Epub 2020 May 22.

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

Brian R Blank  1 , Ian P Andrews  1 , Ohyun Kwon  1
Affiliations

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

Brian R Blank et al. ChemCatChem. .

Abstract

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.

Keywords: (4+1) annulation; 3-pyrroline; phosphine catalysis; phosphonium diene; pyrrolizidine alkaloid.

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Conflict of interest statement

Conflict of Interest The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Representative pyrrolizidine alkaloids.
Scheme 1.
Scheme 1.
Phosphine-catalyzed (4+1) reactions.
Scheme 2.
Scheme 2.
Conversion of allenylic carbamate 1 to phosphonium diene 2 and 3-pyrroline 3.
Scheme 3.
Scheme 3.
Mechanistic rationale for the formation of allenoate 12 from allenylic acetate 9 in the absence of Cs2CO3.
Scheme 4.
Scheme 4.
Plausible mechanism for Tong’s (4+1) reaction.
Scheme 5.
Scheme 5.
Plausible alternative mechanism for Tong’s (4+1) reaction.
Scheme 6.
Scheme 6.
Alternative pathway for the production of intermediate 22.
Scheme 7.
Scheme 7.
Reaction between allenylic acetate 9 and 19 in the presence of Cs2CO3.
Scheme 8.
Scheme 8.
Proposed mechanism for our phosphine-catalyzed (4+1) reaction.
Scheme 9.
Scheme 9.
Reaction of benzyl tosyl carbamate (39) with PPh3.
Scheme 10.
Scheme 10.
Formal synthesis of (±)-trachelanthamidine.
Scheme 11.
Scheme 11.
Formal synthesis of (±)-supinidine.
See this image and copyright information in PMC

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