Tom Sheppard Group - Professor Product Portal

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Professor Tom Sheppard

Our laboratory is interested in the development of new synthetic methodology and its application to the synthesis of potentially useful molecules. Our research work is spread across a wide range of different areas including transition-metal catalysis (gold, palladium), organoboron chemistry, organocatalysis, multicomponent reactions, and sustainable chemistry.

A common theme in many of the ongoing research projects is the development of new methods for activation or formation of carbon-oxygen bonds. Within this class of reactions, the direct synthesis of amides from carboxylic acids and amines is one of the most important and commonly used reactions in organic chemistry. In our laboratory, we have reported the use of simple borate esters for the direct catalytic formation of amides from a wide variety of carboxylic acids and amines. In particular, B(OCH2CF3)3 is highly effective, and can be used for coupling pharmaceutically relevant substrates containing heterocycles and other functional groups. It can even be employed for the catalytic direct amidation of unprotected amino acids. In most cases, the amide products can be purified using a simple solid-phase work-up with acidic, basic and boron-scavenger resins without the need for an aqueous work-up or chromatography. The reactions are readily scalable to obtain multigram quantities of material, and are considerably more efficient than most other amidation methods (PMI as low as 5 for the synthesis of an amine on 20 g scale).

Other recent work in the group has included the development of a range of catalytic transformations of propargylic alcohols, largely using the PPh3AuNTf2 catalyst originally developed by Fabian Gagosz. Efficient methods have been developed for the gold-catalyzed conversion of these readily available starting materials into enones, 3-alkoxyfurans and dihalohydroxyketones; direct substitution of the propargyl alcohol with a variety of nucleophiles can also be achieved using either a silver catalyst or a simple Brønsted acid.

Sheppard Group Website

Products available at Aldrich from the Sheppard Laboratory

     

Sabatini MT1, Boulton LT2, Sheppard TD1.
Sci Adv. 2017 Sep 22;3(9):e1701028. doi: 10.1126/sciadv.1701028. eCollection 2017 Sep.
Chemical reactions for the formation of amide bonds are among the most commonly used transformations in organic chemistry, yet they are often highly inefficient. A novel protocol for amidation using a simple borate ester catalyst is reported. The process presents significant improvements over other catalytic amidation methods inRead More
Arkhipenko S1, Sabatini MT2, Batsanov AS3, Karaluka V2, Sheppard TD2, Rzepa HS4, Whiting A1.
Chem Sci. 2018 Jan 2;9(4):1058-1072. doi: 10.1039/c7sc03595k. eCollection 2018 Jan 28.
The generally accepted monoacyloxyboron mechanism of boron-catalysed direct amidation is brought into question in this study, and new alternatives are proposed. We have carried out a detailed investigation of boron-catalysed amidation reactions, through study of the interaction between amines/carboxylic acids and borinic acids, Read More
Foster RW1, Tame CJ2, Bučar DK1, Hailes HC3, Sheppard TD4.
Chemistry. 2015 Nov 2;21(45):15947-50. doi: 10.1002/chem.201503510. Epub 2015 Sep 25.
L-Arabinose is an abundant resource available as a waste product of the sugar beet industry. Through use of a hydrazone-based strategy, L-arabinose was selectively dehydrated to form a chiral tetrahydrofuran on a multi-gram scale without the need for protecting groups. This approach was extended to other biomass-derived reducingRead More