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Review
. 2024 Jun 11;14(1):37.
doi: 10.1007/s13659-024-00457-9.

Recent advances in the application of [2 + 2] cycloaddition in the chemical synthesis of cyclobutane-containing natural products

Song-Yu Hou  1 , Bing-Chao Yan  1 , Han-Dong Sun  1 , Pema-Tenzin Puno  2
Affiliations
Review

Recent advances in the application of [2 + 2] cycloaddition in the chemical synthesis of cyclobutane-containing natural products

Song-Yu Hou et al. Nat Prod Bioprospect. .

Abstract

Cyclobutanes are distributed widely in a large class of natural products featuring diverse pharmaceutical activities and intricate structural frameworks. The [2 + 2] cycloaddition is unequivocally the primary and most commonly used method for synthesizing cyclobutanes. In this review, we have summarized the application of the [2 + 2] cycloaddition with different reaction mechanisms in the chemical synthesis of selected cyclobutane-containing natural products over the past decade.

Keywords: Cyclobutane; Natural products; Total synthesis; [2 + 2] Cycloaddition.

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Conflict of interest statement

All the authors declare that there is no competitive interest related to this work.

Figures

Scheme 1
Scheme 1
Representative drugs and natural products containing cyclobutane motifs
Scheme 2
Scheme 2
[2 + 2] cycloaddition between alkene and ketene in the synthesis of ( −)-isoscopariusin A
Scheme 3
Scheme 3
[2 + 2] cycloaddition between alkene and keteniminium ions in the synthesis of ( −)-isoscopariusin A
Scheme 4
Scheme 4
Intramolecular [2 + 2] cycloaddition between alkene and allene in the synthesis of ( −)-cajanusine
Scheme 5
Scheme 5
Total synthesis of ( −)-hebelophyllene E
Scheme 6
Scheme 6
Total synthesis of ( +)-hippolide J
Scheme 7
Scheme 7
Total synthesis of hippolachnin A
Scheme 8
Scheme 8
Scopariusicides A, B and its proposed biosynthesis
Scheme 9
Scheme 9
Total synthesis of scopariusicide A
Scheme 10
Scheme 10
Total synthesis of aquatolide by Takao
Scheme 11
Scheme 11
Total synthesis of aplydactone by Zhang
Scheme 12
Scheme 12
Mechanism of the direct photocatalytic [2 + 2] cycloaddition and EnT pathway
Scheme 13
Scheme 13
EnT mediated [2 + 2] cycloaddition by T.P.Yoon
Scheme 14
Scheme 14
EnT mediated [2 + 2] cycloaddition in the total synthesis of ( +)-isoscopariusins B and C
Scheme 15
Scheme 15
Photocatalytic [2 + 2] cycloaddition in the total synthesis of artochamin J
Scheme 16
Scheme 16
Total synthesis of piperarborenine B
Scheme 17
Scheme 17
Total synthesis of isatiscycloneolignan A
Scheme 18
Scheme 18
Total synthesis of barbarumamide C
Scheme 19
Scheme 19
EnT mediated [2 + 2] cycloaddition in the total synthesis of sceptrin
Scheme 20
Scheme 20
Mechanism of the [2 + 2] cycloaddition mediated by SET
Scheme 21
Scheme 21
SET mediated intramolecular [2 + 2] cycloaddition by T.P. Yoon
Scheme 22
Scheme 22
SET mediated intramolecular [2 + 2] cycloaddition in the total synthesis of ( ±)-nyingchinoid D by George
Scheme 23
Scheme 23
Total Synthesis of endiandrin A and di-O-methylendiandrin A
Scheme 24
Scheme 24
Cu(ClO4)2·6H2O mediated intramolecular [2 + 2] cycloaddition in the total synthesis of ( +)-piperarborenine B
Scheme 25
Scheme 25
Total Synthesis of six meroterpenoids by Fe-catalyzed [2 + 2] cycloaddition
Scheme 26
Scheme 26
Non-classic intermolecular [2 + 2] cycloaddition between coumarin analogs and high-tensile bicyclo[1.1.0]butane derivatives
Scheme 27
Scheme 27
Non-classic intermolecular [2 + 2] cycloaddition in the total synthesis of hippolachnin A
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