Catalytic Asymmetric Claisen Rearrangements. The Development of Ru(II)-Catalyzed Formal [3,3] Sigmatropic Rearrangements and Related Enolate Allylation Reactions

The Claisen rearrangement, a [3,3] sigmatropic rearrangement, remains an important method for the construction of C-C bonds nearly a century after its discovery. However, methods to affect a catalytic and asymmetric variant of this reaction are rare. A transition metal/Lewis acid co-catalyst system (Ru(II)-B(III)) has been successfully employed to affect an enantioselective, and diastereoselective Claisen rearrangement of simple, achiral, allyl vinyl ethers without the need for auxiliary functionality to assist in substrate-catalyst association. In addition, we have developed a complementary ruthenium catalyzed enolate allylic alkylation reaction that forms Claisen-like products, without the need to synthesize allyl vinyl ethers

Design and Development of Fe-Catalyzed Intra- and Intermolecular Carbofunctionalization of Vinyl Cyclopropanes

Design and implementation of the first (asymmetric) Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes (VCPs) with alkyl halides and aryl Grignard reagents has been realized via a mechanistically driven approach. Mechanistic studies support the diffusion of the alkyl radical intermediates out of the solvent cage to participate in an intra- or -intermolecular radical cascade with the VCP followed by re-entering the Fe radical cross-coupling cycle to undergo selective C(sp2)-C(sp3) bond formation. Overall, we provide new design principles for Fe-mediated radical processes and underscore the potential of using combined computations and experiments to accelerate the development of challenging transformations

Fe-Catalyzed Conjunctive Cross-Couplings of Unactivated Alkenes with Grignard Reagents

The first iron-catalyzed three-component cross-coupling of unactivated olefins with alkyl halides and Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp2-hybridized nucleophiles, alkyl halides, and unactivated olefins bearing diverse functional groups to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines via a three-component radical cascade cyclization/arylation that forges three new C-C bonds

Gold(I)-Catalyzed Desymmetrization of 1,4-Dienes by an Enantioselective Tandem Alkoxylation/Claisen Rearrangement

An enantioselective alkoxylation/Claisen rearrangement reaction was achieved by a strategic desymmetrization of 1,4-dienes under the catalysis of (S)-DTBM-Segphos(AuCl)(2)/AgBF(4). This reaction system was highly selective for the formation of 3,3-rearrangement products, providing cycloheptenes with various substitutions in good yield and good to excellent enantioselectivity. This transformation was further extended to bicyclic ring substrates, providing the opportunity to easily assemble 5,6- and 6,7-fused ring systems