Synthesis of Spirooxindoles via the tert-Amino Effect.

A new method is developed for the synthesis of spirooxindoles from amines and isatins via C-H functionalization. The reaction leverages the tert-amino effect to form an enolate-iminium intermediate via [1,5]-hydride shift followed by cyclization. Interestingly the hydride migrates to the N atom of a C═N, which is atypical for hydride additions to imines.

Palladium-Catalyzed Double-Decarboxylative Addition to Pyrones: Synthesis of Conjugated Dienoic Esters.

An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct.

Retro-Claisen benzylation: direct use of benzyl alcohols in Pd-catalyzed couplings with nitriles.

A new strategy has been developed for the benzylation of nitriles directly from benzyl alcohols. In this process benzyl alcohols undergo retro-Claisen activation with cyanoacetic esters to generate an active electrophile and a carbanionic nucleophile. In the presence of Pd(0) these intermediates undergo catalytic coupling to generate a new C-C bond, resulting in the formation of phenyl propionitriles.

Catalytic α-monoallylation of aryl acetonitriles.

α-Cyano aldehydes undergo selective transition-metal-catalyzed monoallylation to provide α-allylated nitriles. The transformation leads to linear substitution products with palladium catalysts or branched allylated nitriles using an iridium catalyst. Facile TBD-catalyzed retro-Claisen cleavage is leveraged to attain selective monoallylation.

Development of asymmetric deacylative allylation.

Herein we present the development of asymmetric deacylative allylation of ketone enolates. The reaction directly couples readily available ketone pronucleophiles with allylic alcohols using facile retro-Claisen cleavage to form reactive intermediates in situ. The simplicity and robustness of the reaction conditions is demonstrated by the preparation of >6 g of an allylated tetralone from commercially available materials. Furthermore, use of nonracemic PHOX ligands allows intermolecular formation of quaternary stereocenters directly from allylic alcohols.

L-Proline/CoCl2-catalyzed highly diastereo- and enantioselective direct aldol reactions.

The CoCl(2)/L-proline (1:2) system was found to be an excellent catalyst for direct aldol reactions. Excellent yields (up to 93%) and a significant improvement in diastereoselectivity (anti/syn up to 45:1) as well as enantioselectivity (up to more than 99% ee) compared with using proline as the sole catalyst were observed. This catalyst system was successfully applied to both cyclic and acyclic ketones in combination with aromatic and aliphatic aldehydes. In situ chelation of CoCl(2) and proline (1:2) is proposed to promote the reaction through a six-membered Zimmermann-Traxler type transition state involving the positioning of proline-enamine and the aldehyde through chelation to Co(II).

Visible-light photoredox catalysis: dehalogenation of vicinal dibromo-, α-halo-, and α,α-dibromocarbonyl compounds.

vic-Dibromo-, α-halo-, or α,α-dibromocarbonyl compounds can be efficiently dehalogenated using catalytic tris(2,2'-bipyridyl)ruthenium dichloride (Ru(bpy)(3)Cl(2)) in combination with 1,5-dimethoxynaphthalene (DMN) and ascorbate as sacrificial electron donor. For this process, a visible light promoted photocatalytic cycle is proposed that involves the reduction of carbon halogen bonds via free radical intermediates.

Iron(II)-bis(isonitrile) complexes: novel catalysts in asymmetric transfer hydrogenations of aromatic and heteroaromatic ketones.

Chiral iron(ii)-bis(isonitrile) complexes catalyse the transfer hydrogenation of aromatic ketones with enantioselectivities up to 91% ee, most likely via hydride transfer through imine intermediates, generated by in situ reduction of the isonitrile ligands, whereas iron acts as a Lewis acid to activate the ketone.