Efficient and scalable enantioselective synthesis of a CGRP antagonist.

An enantioselective synthesis of the CGRP antagonist BMS-846372, amenable to large scale preparation, is presented. This new synthesis showcases a chemo- and enantioselective reduction of a cyclohepta[b]pyridine-5,9-dione as well as a Pd-catalyzed alpha-arylation reaction to form the key carbon-carbon bond and set the absolute and relative stereochemistry.

Insights into directing group ability in palladium-catalyzed C-H bond functionalization.

This paper describes a detailed investigation of factors controlling the dominance of a directing group in Pd-catalyzed ligand-directed arene acetoxylation. Mechanistic studies, involving reaction kinetics, Hammett analysis, kinetic isotope effect experiments, and the kinetic order in oxidant, have been conducted for a series of different substrates. Initial rates studies of substrates bearing different directing groups showed that these transformations are accelerated by the use of electron-withdrawing directing groups.

Oxone as an inexpensive, safe, and environmentally benign oxidant for C-H bond oxygenation.

[reaction: see text] This paper describes the application of peroxide-based oxidants in the Pd(OAc)(2)-catalyzed acetoxylation and etherification of arene and alkane C-H bonds. Oxone in acetic acid and/or methanol proved particularly effective, and these transformations were applied to a wide variety of substrates.

Oxidative C-H activation/C-C bond forming reactions: synthetic scope and mechanistic insights.

This paper describes a new palladium-catalyzed method for C-H activation/carbon-carbon bond formation with hypervalent iodine arylating agents. This transformation has been applied to a variety of arene and benzylic substrates containing different directing groups (pyridines, quinolines, oxazolidinones, and amides) and proceeds with high levels of regiocontrol. Mechanistic experiments provide preliminary evidence in support of an unusual mechanism for this transformation involving a Pd(II)/Pd(IV) catalytic cycle.

Palladium-catalyzed oxygenation of unactivated sp3 C-H bonds.

This communication describes a new palladium-catalyzed method for the oxygenation of unactivated sp3 C-H bonds. A wide variety of alkane substrates containing readily available oxime and/or pyridine directing groups are oxidized with extremely high levels of chemo-, regio-, and in some cases diastereoselectivity. The substrate scope of these reactions is discussed, and the high selectivities are rationalized on the basis of the requirements of putative palladium alkyl intermediates.

Substrate selectivity and conformational space available to bromoxynil and acrylonitrile in iron nitrile hydratase.

Nitrile hydratase (NHase) is used in the commercial conversion of acrylonitrile to acrylamide. There are two main types of NHase: the iron containing and the cobalt containing NHase. They catalyze the conversion of a wide variety of nitriles to their corresponding amides.