The modification of benzylic quaternary, tertiary, and secondary carbon centers through palladium‐catalyzed hydrogenolysis of C(sp3)–C(sp3) σ bonds is presented. When benzyl Meldrum's acid derivatives bearing quaternary benzylic centers are treated under mild hydrogenolysis conditions – palladium on carbon and atmospheric pressure of hydrogen – aromatics substituted with tertiary benzylic centers and Meldrum's acid are obtained with good to excellent yield. Analogously, substrates containing tertiary or secondary benzylic centers yield aromatics substituted with secondary benzylic centers or toluene derivatives, respectively. Furthermore, this strategy is used for the high yielding synthesis of diarylmethanes. The scope of the reductive dealkylation reaction is explored and the limitations with respect to steric and electronic factors are determined. A mechanistic analysis of the reaction is described that consisted of deuterium labelling experiments and hydrogenolysis of enantioenriched derivatives. The investigation shows that the C(sp3)–C(sp3) σ bond‐cleaving events occur through a hybrid SN1/SN2 mechanism, in which the palladium center displaces a carbon‐based leaving group, namely Meldrum's acid, with inversion of configuration, followed by reductive elimination of palladium to furnish a C−H bond.magnified image
This article describes the catalytic asymmetric formation of all carbon benzylic quaternary centres, which is an important goal in organic chemistry as these moieties are ubiquitous in natural products and pharmaceuticals. Conjugate addition of organometallic reagents to tri‐ and tetrasubstituted alkenes activated by carbonyl, nitro or sulfone groups is an efficient method that can be used to synthesize these motifs. The conjugate addition of dialkylzinc reagents to 5‐ylidene Meldrum's acid derivatives presented herein is a flexible and convenient method to perform this transformation because the substrates are readily prepared by Knoevenagel condensation of various commercially available aryl ketones and the conjugate addition products may undergo a wide variety of transformations. In addition, the substrate scope is broad as the reaction tolerates numerous functional groups.
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