Massachusetts Institute of Technology

Merck Sharp + Dohme Corp.

Michael Palucki

Stephen L Buchwald

John P Wolfe

Ken Kamikawa

David W Old

Ian W Davies

Jonathan D Rosen

Jens Bertil Ahman

Dietrich P Steinhuebel

Malisa Troutman

Andre Chieffi

An efficient syntheses for the preparation of (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one.

Process for the preparation of caprolactam CGRP antagonist

One aspect of the present invention relates to novel ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.

Ligands for metals and improved metal-catalyzed processes based thereon

The present invention provides transition-metal-catalyst-based methods for the arylation and vinylation of activated methyl, methylene, and methine carbons with aryl halides, vinyl halides, and the like. The methods of the invention provide several improvements over existing methods, including the ability to synthesize efficiently and under mild conditions &#x3b1;-aryl and &#x3b1;-vinyl products from a wide range of starting materials, including ketones, esters, hydrazones, and imines. Furthermore, the methods of the invention may be used in an asymmetric sense, i.e. to produce enantiomerically-enriched chiral &#x3b1;-aryl and &#x3b1;-vinyl products.

Arylation and vinylation of activated carbons

One aspect of the present invention relates to novel, electron-rich bidentate ligands for transition metals. A second aspect of the present invention relates to the use of catalysts comprising these ligands in transition metal-catalyzed carbon-heteroatom and carbon-carbon bond-forming reactions. The subject methods provide improvements in many features of the transition metal-catalyzed reactions, including the range of suitable substrates, reaction conditions, and efficiency.

A method for preparing an aryl ether compound is provided in which an alcohol is reacted with an aromatic compound in the presence of a base, and a transition metal catalyst selected from the group consisting of platinum and nickel to form an aryl ether. The aromatic compound comprises an activated substituent, X, said activated substituent being a moiety such that its conjugate acid HX has a pKa of less than 5.0. The catalyst is preferably a soluble palladium complex in the presence of supporting ligands.

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Belle Meade, NJ, United States of America

Michael Palucki