Catalytic Enantioselective [2+2] Cycloaddition of α‐Halo Acroleins: Construction of Cyclobutanes Containing Two Tetrasubstituted Stereocenters

Abstract

A catalytic enantioselective formal [2+2] cycloaddition between a-halo acroleins and electronically diverse arylalkenes is described. In the presence of (S)-oxazaborolidinium cation as the catalyst, densely functionalized cyclobutanes containing two vicinal tetrasubstituted stereocenters were produced in high yields and high diastereoselectivities with excellent enantioselectivities. Mechanistic studies revealed that the cis isomer could be transformed into the trans isomer via an enantiocontrolled process. A gram-scale reaction of this catalytic method was used to demonstrate its synthetic potential. Scheme 1. Chiral Lewis acid catalyzed asymmetric [2+2] cycloadditions.

Mechanistic study of cobalt(I)‐catalyzed asymmetric coupling of ethylene and enynes to functionalized cyclobutanes

“…[11][12][13][14][15] Generally, there are two approaches for generating cyclobutane derivatives with stereocenters, including the enantioselective ring closure reactions [16][17][18] and the enantioselective functionalization of prochiral cyclobutane or cyclobutene speices. 19,20 For the cycloaddition reactions of alkenes or alkynes, the efficient catalysts could be photoinduction, [21][22][23][24] Lewis acids 25 or transition metal compounds. [26][27][28] However, the direct use of ethylene for synthesizing cyclobutane was hardly reported except for the reported Fe(0)-catalyzed the cycloaddition reaction of butadiene and ethylene giving the achiral cyclobutene.…”

Catalytic Diastereoselective Hetero-Diels–Alder Reaction of α-Haloacroleins with Alkenes: Construction of 3,4-Dihydropyran

“…Then, we examined the electronic effect of the phenyl ring with a series of para-substituted styrenes. Except for those with a strong electron-withdrawing group (14 and 15), styrenes bearing substituents including the strong electron-donating −OMe were quite suitable in the catalytic reaction (9)(10)(11)(12)(13)16). meta-and ortho-Chloro styrenes delivered products in relatively low yields (17 and 18).…”

“…The reaction is always complex and leads to the formation of a mixture of products . The ene reaction, especially stepwise cyclobutanation, has always accompanied HDA reactions. , In view of the long-standing limitation of the substrate scope in the REDF HDA reaction, here we disclose a catalytic protocol that successfully expands the substrate scope to acroleins with less polarized alkenes (Scheme ).…”

Oxathiaborolium-catalyzed enantioselective [2 + 2] cycloadditions

“…11–13 Therefore, significant effort has recently been devoted to exploring a number of enantioselective strategies. Among these endeavors, catalytic enantioselective [2 + 2] cycloaddition chemistry provides the most economical and sustainable approach for constructing chiral cyclobutane derivatives, 14–35 and Lewis-acid-catalyzed [2 + 2] cycloadditions between electron-deficient olefins and alkenes are highly attractive. 36–41 Several catalytic asymmetric strategies have been documented following the pioneering work on catalytic enantioselective [2 + 2] cycloadditions reported by Narasaka et al (Scheme 1).…”

“…[36][37][38][39][40][41] Several catalytic asymmetric strategies have been documented following the pioneering work on catalytic enantioselective [2 + 2] cycloaddi-tions reported by Narasaka et al (Scheme 1). [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In addition, many enantioselective photochemical [2 + 2] cycloaddition reactions have been reported for the synthesis of optically active cyclobutane moieties over the past few years. [42][43][44][45][46][47][48][49] Furthermore, a few groups have reported some enantioselective organocatalytic strategies that provide easy access to functionalized cyclobutane derivatives.…”