Lewis Acid/Base Catalyzed [2+2]‐Cycloaddition of Sulfenes and Aldehydes: A Versatile Entry to Chiral Sulfonyl and Sulfinyl Derivatives

Abstract

The first catalytic asymmetric synthesis of β-sultones is reported. This development has enabled a rapid access to a number of highly enantioenriched biologically interesting sulfonyl and sulfinyl compound classes, which makes use of the inherent ring strain of the four-membered heterocycles. The products possess either two vicinal stereocenters, such as in β-hydroxy-sulfonamides, -sulfonates, -sulfones, -sulfonic acids, -sulfinic acids, γ-sultines, and γ-sultones or a single stereocenter, such as in α-branched alkyl or allyl sulfonic acids. This work also represents the first application of sulfene intermediates in asymmetric catalysis. The reactivity of a sulfene normally acting as an electrophile could be reverted by the formation of a nucleophilic zwitterionic sulfene-amine adduct. To achieve a combination of high enantioselectivity and reactivity, cooperative catalytic action of a chiral nucleophilic tertiary amine (the cinchona alkaloid derivative diydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQ)(2)PYR)) and Bi(OTf)(3) or In(OTf)(3) was of primary importance.

New trends in bismuth-catalyzed synthetic transformations

“…Cooperative catalytic action of a chiral nucleophilic tertiary amine (the cinchona alkaloid derivative dihydroquinine 2,5diphenyl-4,6-pyrimidinediyl diether [(DHQ) 2 PYR]) and Bi(OTf ) 3 , in the presence of 1,2,2,6,6-pentamethylpiperidine (PMP), was proposed in the [2+2]-cycloaddition of sulfenes and aldehydes. 81 The reaction of propanesulfonyl chloride with chloral provided the disubstituted β-sulfone with high diastereo-and enantioselectivity (Scheme 71). Bi(OTf ) 3 provided better yields (47-87%) than In(OTf ) 3 (28-69%), whereas in terms of enantioselectivity a clear-cut trend is not obvious.…”

Unexpected reactions of Grignard reagents with selected β-carboalkoxy substituted sulfinate esters

“…[28][29][30][31] Diels-Alder reactions with sulfinate ester-bearing dienophiles have also been studied. [32][33][34][35] The sulfinate is particularly appealing for its ability to be readily adapted by reduction, 34,36,37 oxidation, [38][39][40] and transformation to sulfoxide. [41][42][43] Moreover, we have demonstrated that appropriately disposed sulfinate esters can participate in iodosultinization reactions with inversion of sulfinyl configuration.…”

Catalytic Asymmetric Synthesis of Spirocyclic Azlactones by a Double Michael‐Addition Approach

“…[13] In this context we have also reported the first catalytic asymmetric examples, in which the azlactone substrates have been formed in situ from racemic acylated or unprotected amino acids. [13] Results and Discussion Catalytic investigations: As part of our program to study cooperative effects in asymmetric catalysis, [14] we have investigated a planar chiral ferrocene bisimidazoline bispalladacycle (FBIP, prepared in four steps from ferrocene), which has recently been developed and studied in our research group for various bimetal-catalyzed applications. [15][16][17][18] For catalytic Abstract: Spirocyclic azlactones are shown to be useful precursors of cyclic quaternary amino acids, such as the constrained cyclohexane analogues of phenylalanine.…”