Asymmetric Organocatalytic [2,3]‐Wittig Rearrangement of Cyclohexanone Derivatives

Abstract

Asymmetric rearrangement reactions are one of the perfect tools for the construction of new carbon-carbon bonds in an enantioselective manner. The enantioselective [2,3]-Wittig rearrangement of cinnamyloxycyclohexanone derivatives, catalyzed by a commercially available primary amine, provided α-hydroxy ketones with high diastereo-and enantioselectivity. A new and straightforward procedure for the synthesis of cinnamyloxycyclohexanone derivatives was developed.

Primary amines as heterogeneous catalysts in an enantioselective [2,3]-Wittig rearrangement reaction

“…We have recently reported an asymmetric [2,3]-Wittig rearrangement reaction of cyclohexanone derivatives. 26 Utilizing a structurally simple primary amine, substituted α-hydroxyketones were obtained with high yields, diastereoselectivities and enantioselectivities of the major diastereomer ( Scheme 2 ). However, this approach is not devoid of limitations, since the epimerization of the rearrangement product happened under the [2,3]-Wittig rearrangement conditions, diminishing enantioselectivity, especially drastically for the minor diastereomer.…”

“…We started the investigation of the [2,3]-Wittig rearrangement of cyclohexanone derivatives under previously optimized reaction conditions for homogeneous catalysis with immobilized catalysts connected with the resin by an ester bond. 26 Reactions were carried out in CDCl 3 in the presence of a corresponding immobilized catalyst and a catalytic amount of para -nitrobenzoic acid ( p -NBA). The reaction mixture was shaken in a temperature-controlled shaker at 50°C.…”

“…While conducting the [2,3]-Wittig rearrangement reaction in the presence of a homogeneous catalyst, a noticeable drop in the enantioselectivity of the rearranged product was observed. 26 However, performing the same reaction using heterogeneous catalysis led to the formation of the product 2 with significantly higher enantioselectivity of both diastereomers (to compare, ee major/minor for product 2 with homogeneous catalysis – 77%/35%, heterogeneous catalysis – 86%/86%). The kinetic study of the [2,3]-Wittig rearrangement reaction of 1 with the immobilized catalyst XXIX revealed the full consumption of the starting material in 16 h. A decrease in ee of both diastereomers was also noticed, but, compared to the homogeneous catalysis, the detected drop was substantially smaller ( Figure 6 ).…”

“… Limitations associated with the scope of [2,3]-Wittig rearrangement of cyclohexanone derivatives can be found in our prior publication. 26 In this investigation, a heterogeneous catalyst with recyclability of up to six cycles is presented. Subsequent research is warranted to extend the reusability profile of the identified catalytic system.…”

“…Limitations associated with the scope of [2,3]-Wittig rearrangement of cyclohexanone derivatives can be found in our prior publication. 26 …”