Enantioselective Potassium-Catalyzed Wittig Olefinations

Abstract

We report asymmetric potassium−isothiourea−boronate-catalyzed Wittig olefinations of 4-substituted cyclohexanones with non-stabilized phosphorus ylides to afford highly enantioenriched axially chiral alkenes. The optimal catalyst features an unusual macrocyclic amide−potassium−boronate chelate. Kinetic and spectroscopic analyses are consistent with a Lewis acid mechanism for the catalytic olefination that results in the formation of the oxaphosphetane adduct under cryogenic conditions. Thermal fragmentation of the oxaphosphetane to the alkene product occurs after the reaction is complete. Computational studies indicate that cycloaddition proceeds via a stepwise mechanism involving enantiodetermining polar 1,2-addition to afford an intermediate potassium betaine complex.

Stable Axially Chiral Cyclohexylidenes from Catalytic Asymmetric Knoevenagel Condensation

“…Recently, Jacobsen achieved highly enantioenriched axially chiral alkenes by developing an efficient potassiumÀ isothioureaÀ boronate catalyst to promote asymmetric Wittig olefinations of 4-substituted cyclohexanones with non-stabilized phosphorus ylides. [15] In 2019, Bencivenni [14b] applied a cinchona-derived primary amine catalyst to realize the enantioselective Knoevenagel condensation reaction between 4-substituted cyclohexanones and oxindoles. It's a straightforward method to construct axially chiral cyclohexylidene oxindole-derivatives, but suffers from the following problems: 1) the axial chirality is easily destroyed, resulting racemization even during purification process; 2) the enantioselectivity need improving, especially, the prochiral cyclohexanones with small steric hindered aliphatic group transformed in very low enantioselectivities; 3) the substrate scope need being broadened since only oxindoles were reported.…”

Enantioselective Construction of Anthracenylidene-Based Axial Chirality by Asymmetric Heck Reaction

“…The first foray into catalytic asymmetric assembly of this unique structure can be traced back to 1988 when Fiaud and co-workers explored a palladium-catalyzed enantioselective allylic alkylation, albeit with poor enantiocontrol . Despite significant advances in the field, most investigations in this realm have focused on a cyclohexylidene core . Noteworthily, Jacobsen and co-workers ingeniously established an expeditious approach to access this type of axially chiral skeletons harnessing potassium-isothiourea-boronate-catalyzed asymmetric Wittig olefinations very recently .…”