[3,3]-Sigmatropic rearrangements: recent applications in the total synthesis of natural products

Abstract

Among the fundamental chemical transformations in organic synthesis, the [3,3]-sigmatropic rearrangement occupies a unique position as a powerful, reliable, and well-defined method for the stereoselective construction of carbon-carbon or carbon-heteroatom bonds. While many other reactions can unite two subunits and create a new bond, the strengths of sigmatropic rearrangements derive from their ability to enable structural reorganization with unmatched build-up of complexity. Recent applications that illustrate [3,3]-sigmatropic processes as a key concept in the synthesis of complex natural products are described in this tutorial review, covering literature from about 2001 through early 2009.

Fig. 1

A summary of natural products discussed in this review.

Fig. 2

By-products in the isomerization of 71.

Scheme 1

C-H activation-Cope rearrangement strategy in the synthesis of (−)-colombiasin A and (−)-elisapterosin B.

Scheme 2

Tandem oxy-Cope–Claisen–ene reorganization of 10 in an approach to wiedamannic acid.

Scheme 3

Tandem oxy-Cope–ene reaction in the total synthesis of (+)-arteannuin M.

Scheme 4

Formal synthesis of (−)-FR901483 by aza-Cope–Mannich cyclization.

Scheme 5

Aza-Cope–Mannich strategy in the synthesis of (±)-dide-hydrostemofoline and (±)-isodidehydrostemofoline.

Scheme 6

Aza-Cope–Mannich cascade in the synthesis of actinophyllic acid.

Scheme 7

Frondosin B: anionic 5-exo-cyclization–Claisen rearrangement.

Scheme 8

Synthesis of 1-O-methylforbesione.

Scheme 9

Total synthesis of (±)-1-O-methyllateriflorone (65).

Scheme 10

Total synthesis of (±)-gambogin.

Scheme 11

Total synthesis of solandelactones.

Scheme 12

Tandem nitrosation–oxaza-Cope rearrangement in the total synthesis of trichodermamide B.

Scheme 13

The synthesis of (±)-clavubicyclone by a Cope rearrangement.

Scheme 14

Oxy-Cope rearrangement in the enantioselective synthesis of alkaloid G and (+)-ajmaline.

Scheme 15

Synthesis of (±)-eremopetasidione.

Scheme 16

The Claisen rearrangement of ester 142 in the synthesis of (+)-pinnatoxin A.

Scheme 17

A unified total synthesis of (−)-joubertinamine and (−)-mesembrine.

Scheme 18

Claisen rearrangement in the synthesis of (+)-galanthamine.

Scheme 19

Claisen rearrangement as a key step in the total synthesis of azadirachtin.

Scheme 20

Scheme 21

The total synthesis of communesin F.

Scheme 22

Stereocontrol through complexation in the Claisen rearrangement en route to saudin.

Scheme 23

Zaragozic acid C.

Scheme 24

Consecutive sigmatropic rearrangements in the synthesis of A-315675.

Scheme 25

Allyic cyanate to isocyanate rearrangement in the synthesis of glycocinnasperimicin D.

Scheme 26

[3,3]-Sigmatropic transposition of N-vinyl-2-arylaziridine in the total synthesis of (−)-deoxyharringtonine.