Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

Abstract

Cyclopropenes constitute useful precursors of other classes of compounds incorporating a three-membered ring. Although the transformation of substituted cyclopropenes into alkylidenecyclopropanes can be accomplished through different strategies, this review is focusing specifically on the use of [2,3]- and [3,3]-sigmatropic rearrangements involving cyclopropenylcarbinol derivatives as substrates. These sigmatropic rearrangements, which have been developed in recent years, allow a remarkably efficient and stereoselective access to a wide variety of heterosubstituted and/or functionalized alkylidenecyclopropanes which would not be readily accessible by other strategies. The different [2,3]- and [3,3]-sigmatropic rearrangements of cyclopropenylcarbinol derivatives disclosed to date, as well as the analysis of their substrate scope and some applications of the products arising from those reactions, are presented in this review.

Keywords: alkylidenecyclopropanes; cyclopropanes; cyclopropenes; sigmatropic rearrangements; strained rings.

Scheme 1

Representative strategies for the formation of alkylidenecyclopropanes from cyclopropenes and scope of the review.

Scheme 2

[2,3]-Sigmatropic rearrangement of phosphinites 2a–h.

Scheme 3

[2,3]-Sigmatropic rearrangement of a phosphinite derived from enantioenriched cyclopropenylcarbinol (S)-1f.

Scheme 4

Selective reduction of phosphine oxide (E)-3f.

Scheme 5

Attempted thermal [2,3]-sigmatropic rearrangement of phosphinite 6a.

Scheme 6

Computed activation barriers and free enthalpies.

Scheme 7

[2,3]-Sigmatropic rearrangement of phosphinites 6a–j.

Scheme 8

Proposed mechanism for the Lewis base-catalyzed rearrangement of phosphinites 6.

Scheme 9

[3,3]-Sigmatropic rearrangement of tertiary cyclopropenylcarbinyl acetates 10a–c.

Scheme 10

[3,3]-Sigmatropic rearrangement of secondary cyclopropenylcarbinyl esters 10d–h.

Scheme 11

[3,3]-Sigmatropic rearrangement of trichoroacetimidates 12a–i.

Scheme 12

Reaction of trichloroacetamide 13f with pyrrolidine.

Scheme 13

Catalytic hydrogenation of (arylmethylene)cyclopropropane 13f.

Scheme 14

Instability of trichloroacetimidates 21a–c derived from cyclopropenylcarbinols 20a–c.

Scheme 15

[3,3]-Sigmatropic rearrangement of cyanate 27 generated from cyclopropenylcarbinyl carbamate 26.

Scheme 16

Synthesis of alkylidene(aminocyclopropane) derivatives 30–37 from carbamate 26.

Scheme 17

Scope of the dehydration–[3,3]-sigmatropic rearrangement sequence of cyclopropenylcarbinyl carbamates.

Scheme 18

Formation of trifluoroacetamide 50 from carbamate 49.

Scheme 19

Formation of alkylidene[(N-trifluoroacetylamino)cyclopropanes] 51–54.

Scheme 20

Diastereoselective hydrogenation of alkylidenecyclopropane 51.

Scheme 21

Ireland–Claisen rearrangement of cyclopropenylcarbinyl glycolates 56a–l.

Scheme 22

Synthesis and Ireland–Claisen rearrangement of glycolate 61 possessing gem-diester substitution at C3.

Scheme 23

Synthesis of alkylidene(gem-difluorocyclopropanes) 66a–h, and 66k–n from propargyl glycolates 64a–n.

Scheme 24

Ireland–Claisen rearrangement of N,N-diBoc glycinates 67a and 67b.

Scheme 25

Diastereoselective hydrogenation of alkylidenecyclopropanes 58a and 74.

Scheme 26

Synthesis of functionalized gem-difluorocyclopropanes 76 and 77 from alkylidenecyclopropane 66a.

Scheme 27

Access to oxa- and azabicyclic compounds 78–80.