Asymmetric Hydrogenation of Pyrroles

The asymmetric hydrogenation of pyrroles is a useful method to optically active pyrrolidines that are building blocks of pyrroline based alkaloids and otlier biolog ically active compounds. It was not until very recently that the catalytic asymmetric hydrogenation of pyrroles has become the truth. 

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Approach C, direct asymmetric hydrogenation of pyrrole 4, had no precedent at the time, and was deemed to require extensive development. Only recently, the first successful cases of asymmetric hydrogenation of certain pyrroles have been reported by Kuwano (Scheme 8.7) [9]. 

Enantioselective hydrogenation of pyrroles has also been conducted, and is somewhat more complex than that of indoles. These reactions were conducted with N-Boc-substituted pyrroles and a ruthenium-TRAP catalyst. The pyrroles can be mono-, di-, or tri-substituted. For example, the asymmetric reduction of 4,5-dimethylpyrrole-2-carboxylate gave the product from addition of hydrogen to the same face of both olefin units to form products containing three stereocenters in high enantioselectivity. These reactions occur by initial reduction of the less-substituted carbon-carbon double bond. 

Modification of the core motif allows for 2,5-diamido-pyrrole derivatives, 99, having a additional NH hydrogen-bond donor compared with isophthalamide receptors. A binding constant of 2500 M for benzoate in acetonitrile is observed with an asymmetric binding mode apparent in the molecular structure measured by X-ray crystallography. 

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