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. 2021 Nov 17;143(45):18864-18870.
doi: 10.1021/jacs.1c10175. Epub 2021 Nov 8.

Stereoselective Synthesis of Cyclobutanes by Contraction of Pyrrolidines

Chunngai Hui  1   2 , Lukas Brieger  2 , Carsten Strohmann  2 , Andrey P Antonchick  1   2   3
Affiliations

Stereoselective Synthesis of Cyclobutanes by Contraction of Pyrrolidines

Chunngai Hui et al. J Am Chem Soc. .

Abstract

Here we report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. Mediated by a nitrogen extrusion process, the stereospecific synthesis of cyclobutanes involves a radical pathway. Unprecedented unsymmetrical spirocyclobutanes were prepared successfully, and a concise, formal synthesis of the cytotoxic natural product piperarborenine B is reported.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Cyclobutane containing bioactive natural products. (B) Stereospecific synthesis of cyclobutanes via 1,1-diazene. (C) Iodonitrene chemistry. (D) Chemical features of this work.
Scheme 1
Scheme 1. Scope of Contractive Synthesis of Multisubstituted Cyclobutanes from Pyrrolidines
Using 5 equiv of HTIB for 12 h. XRD denotes X-ray diffraction analysis (for details, see the Supporting Information).
Scheme 2
Scheme 2. Further Investigation of Contractive Synthesis of Cyclobutanes: (A) Observation of Olefin Side Product Resulting from β-fragmentation; (B) Radical Trapping Experiments Using Various Scavengers; (C) Oxidative Ring Contraction of N-Aminopyrrolidine; (D) Attempts of Nitrogen Deletion from a Linear Secondary Amine; (E) Proposed Reaction Mechanism
Scheme 3
Scheme 3. Formal Stereoselective Synthesis of Piperarborenine B (3)
See this image and copyright information in PMC

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