Stereoselective Gold(I)-Catalyzed Vinylcyclopropanation via Generation of a Sulfur-Substituted Vinyl Carbene Equivalent.

A stereoselective gold(I)-catalyzed vinylcyclopropanation of alkenes has been developed. A gold-coordinated cationic vinyl carbene species, readily generated via a rearrangement of the ethylenedithioacetal of propargyl aldehyde, reacts with a wide range of alkenes to afford thio-substituted vinylcyclopropanes. The gold-catalyzed vinyl cyclopropanation proceeds under mild conditions at room temperature and is generally selective for the formation of cis-substituted cyclopropanes. The reaction allows the formal introduction of a "naked" vinyl carbene, by subsequent chemoselective hydrodesulfurisation of the ethylenedithio-bridge. The synthetic utility of the new method is demonstrated by a short, racemic formal synthesis of the alkaloid cephalotaxin, hinging on a key vinyl cyclopropane-cyclopentene rearrangement.

Chiral Primary Amine Catalysis for Asymmetric Mannich Reactions of Aldehydes with Ketimines: Stereoselectivity and Reactivity.

The application potential of primary amine catalysts in the context of Mannich reactions of aldehydes with ketimines is exemplified by isatin-derived ketimines and cyclic trifluoromethyl ketimines. Primary amine catalysts exhibit either unusual stereoselectivity or reactivity, which is not observable with secondary amine catalysts. Moreover, reversal of diastereofacial selectivity between primary and secondary amine catalysts is disclosed. These new reactions provide useful methods for the syntheses of chiral 3-substituted 3-amino-2-oxindoles and dihydroquinazolinones bearing a trifluoromethylated quaternary stereocenter. The synthetic utility of the reactions is demonstrated through the formal synthesis of AG-041R and DPC 083 and the total synthesis of (-)-psychotriasine.

Dearomative (3 + 2) Cycloaddition of Indoles for the Stereoselective Assembly of Fully Functionalized Cyclopentanoids.

The gold(I)-catalyzed dearomative cyclopentannulation of various indoles with 2-ethynyl-1,3-dithiolane is reported. The method generates three new stereocenters with excellent control of relative stereochemistry and is tolerant of diverse functionalization and substitution patterns on the indoles. The obtained cyclopentane-fused indolines allow for interesting subsequent synthetic manipulations, giving rise to fully substituted cyclopentanes with control of the relative stereochemistry of all five stereocenters. The reported reaction illustrates and elucidates a mechanistic dichotomy underlying gold(I)-catalyzed reactions of 2-ethynyl-1,3-dithiolane.

C(sp3)-H Monoarylation of Methanol Enabled by a Bidentate Auxiliary.

With the assistance of a practical directing group (COAQ), the first catalytic protocol for the palladium-catalyzed C(sp3)-H monoarylation of methanol has been developed, offering an invaluable synthesis means to establish extensive derivatives of crucial arylmethanol functional fragments. Furthermore, the gram-scale reaction, broad substrate scope, excellent functional group compatibility, and even the practical synthesis of medicines further demonstrate the usefulness of this strategy.

Cobalt-Catalyzed C-H Acetoxylation of Phenols with Removable Monodentate Directing Groups: Access to Pyrocatechol Derivatives.

An efficient cobalt-catalyzed C-H acetoxylation of phenols has been developed by using PIDA (phenyliodine diacetate) as a sole acetoxy source to synthesize pyrocatechol derivatives for the first time. The key feature of this method is the use of earth-abundant metal cobalt as the green and inexpensive catalyst for the acetoxylation of C(sp2)-H bonds under neutral reaction conditions. Furthermore, the gram-scale reaction and late-stage functionalization demonstrated the usefulness of this method.