A 1,3,2-Diazaphospholene-Catalyzed Reductive Claisen Rearrangement.

1,3,2-Diazaphospholenes (DAPs) are an emerging class of organic hydrides. In this work, we exploited them as efficient catalysts for very mild reductive Claisen rearrangements. The method is tolerant towards a wide variety of functional groups and operates at ambient temperature. Besides being enantiospecific for substrates with existing stereogenic centers, the diastereoselectivity can be switched by varying solvents and DAP catalysts. The reaction kinetics show direct rearrangements of O-bound phospholene enolates and provide a proof-of-principle for catalytic enantioselective reactions.

Chiral 1,3,2-Diazaphospholenes as Catalytic Molecular Hydrides for Enantioselective Conjugate Reductions.

Secondary 1,3,2-diazaphospholenes have a polarized P-H bond and are emerging as molecular hydrides. Herein, a class of chiral, conformationally restricted methoxy-1,3,2-diazaphospholene catalysts is reported. We demonstrate their catalytic potential in asymmetric 1,4-reductions of α,ß-unsaturated carbonyl derivatives, including enones, acyl pyrroles, and amides, which proceeded in enantioselectivities of up to 95.5:4.5 e.r.

Ligand-controlled regiodivergent nickel-catalyzed annulation of pyridones.

The 1,6-annulated 2-pyridone motif is found in many biologically active compounds and its close relation to the indolizidine and quinolizidine alkaloid core makes it an attractive building block. A nickel-catalyzed C-H functionalization of 2-pyridones and subsequent cyclization affords 1,6-annulated 2-pyridones by selective intramolecular olefin hydroarylation. The switch between the exo- and endo-cyclization modes is controlled by two complementary sets of ligands. Irrespective of the ring size, the regioselectivity during the cyclization is under full catalyst control. Simple cyclooctadiene promotes an exo-selective cyclization, whereas a bulky N-heterocyclic carbene ligand results in an endo-selective mode. The method was further applied in the synthesis of the lupin alkaloid cytisine.

Chiral Cp-rhodium(III)-catalyzed asymmetric hydroarylations of 1,1-disubstituted alkenes.

Metal-catalyzed functionalizations at the ortho position of a directing group have become an efficient bond-forming strategy. A wide range of transformations that employ Cp*Rh(III) catalysts have been described, but despite their synthetic potential, enantioselective variants that use chiral versions of the Cp* ligand remain scarce (Cp*=pentamethyl cyclopentadienyl). Cyclopentadienyl compounds with an atropchiral biaryl backbone are shown to be suitable ligands for the efficient intramolecular enantioselective hydroarylation of aryl hydroxamates. Dihydrofurans that bear methyl-substituted quaternary stereocenters are thus obtained by CH functionalization under mild conditions.

Nickel(0)-catalyzed enantioselective annulations of alkynes and arylenoates enabled by a chiral NHC ligand: efficient access to cyclopentenones.

Cyclopentenones are versatile structural motifs of natural products as well as reactive synthetic intermediates. The nickel-catalyzed reductive [3+2] cycloaddition of α,ß-unsaturated aromatic esters and alkynes constitutes an efficient method for their synthesis. Here, nickel(0) catalysts comprising a chiral bulky C1-symmetric N-heterocyclic carbene ligand were shown to enable an efficient asymmetric synthesis of cyclopentenones from mesityl enoates and internal alkynes under mild conditions. The bulky NHC ligand provided the cyclopentenone products in very high enantioselectivity and led to a regioselective incorporation of unsymmetrically substituted alkynes.

Diaminophosphine oxide ligand enabled asymmetric nickel-catalyzed hydrocarbamoylations of alkenes.

Chiral trivalent phosphorus species are the dominant class of ligands and the key controlling element in asymmetric homogeneous transition-metal catalysis. Here, novel chiral diaminophosphine oxide ligands are described. The arising catalyst system with nickel(0) and trimethylaluminum efficiently activates formamide C-H bonds under mild conditions providing pyrrolidones via intramolecular hydrocarbamoylation in a highly enantioselective manner with as little as 0.25% mol catalyst loading. Mechanistically, the secondary phosphine oxides behave as bridging ligands for the nickel center and the Lewis acidic organoaluminum center to give a heterobimetallic catalyst with superior reactivity.

Synthetic Approach toward Enantiopure Cyclic Sulfinamides.

A synthetic approach toward densely substituted enantiopure cyclic sulfinamides possessing up to four consecutive stereogenic centers was developed based on a completely diastereoselective SN2' cyclization/tert-Bu cleavage sequence. Diastereospecific transformation of the obtained scaffold into chiral SVI derivatives such as sulfoximines and sulfonimidamides is demonstrated.

Efficient synthesis of the 3-benzazepine framework via intramolecular Heck reductive cyclization.

A microwave-assisted protocol based on reductive Heck reaction was developed for regio- and stereoselective construction of the 3-benzazepine core.

Efficient synthesis of the indoloazocine framework via intramolecular alkyne carbocyclization.

A microwave-assisted protocol based on an Hg(OTf)(2) catalyzed intramolecular alkyne carbocyclization reaction was developed for selective construction of the indoloazocine core.