Recent studies have demonstrated that amides can be used in nickel-catalyzed reactions that lead to cleavage of the amide C–N bond, with formation of a C–C or C–heteroatom bond. However, the general scope of these methodologies has been restricted to amides where the carbonyl is directly attached to an arene or heteroarene. We now report the nickel-catalyzed esterification of amides derived from aliphatic carboxylic acids. The transformation requires only a slight excess of the alcohol nucleophile and is tolerant of heterocycles, substrates with epimerizable stereocenters, and sterically congested coupling partners. Moreover, a series of amide competition experiments establish selectivity principles that will aid future synthetic design. These studies overcome a critical limitation of current Ni-catalyzed amide couplings and are expected to further stimulate the use of amides as synthetic building blocks in C–N bond cleavage processes.
A highly-enantioselective acylation of silyl ketene acetals with acyl fluorides has been developed to generate useful α, α-disubstituted butyrolactone products. This reaction is promoted by a new thiourea catalyst and 4-pyrrolidinopyridine and represents the first example of enanti-oselective thiourea anion-binding catalysis with fluoride.
A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.
Synthesis of chiral sulfones: A copper–phosphine complex efficiently provided optically active alkyl phenyl sulfones by hydrosilylation at room temperature. The reduction of β,β‐disubstituted vinyl sulfones in the presence of the Me‐DuPhos monoxide ligand lead to excellent enantiomeric excesses and high yields (see scheme). The prepared chiral sulfones were desulfonylated and subjected to Julia olefination conditions.
A concise asymmetric synthesis of an 11β-HSD-1 inhibitor has been achieved using inexpensive starting materials with excellent step-economy at low catalyst loadings. The catalytic enantioselective total synthesis of 1 was accomplished in 7 steps and 38% overall yield aided by the development of an innovative, sequential strategy involving Pd-catalyzed pyridinium C–H arylation and Ir-catalyzed asymmetric hydrogenation of the resulting fused tricyclic indenopyridinium salt highlighted by the use of a unique P,N-ligand (MeO-BoQPhos) with 1000 ppm of [Ir(COD)Cl]2.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.