Biomedical subjects

Simon J Hedley

Publications and source records attributed to Simon J Hedley.

3 recordsLinked to original sources

PubMed2006

Investigation into factors influencing stereoselectivity in the reactions of heterocycles with donor-acceptor-substituted rhodium carbenoids.

Rhodium-catalyzed decomposition of aryldiazoacetates in the presence of pyrroles or furans results in mono- or biscyclopropanation of the heterocycle, but with opposite enantioinduction. In the absence of sterically encumbering groups, the cyclopropanation of furan occurs with initial bond formation at the 2-position. If this pathway is sterically blocked, cyclopropanation can occur with initial bond formation at the 3-position of the furan ring; in this case, the cyclopropanation reaction takes place on the opposite face of the heterocycle, and the opposite enantioinduction is observed. Upon extension of this methodology to benzofurans, a highly enantioselective monocyclopropanation reaction occurs to furnish a product derived from initial bond formation at the 2-position of the benzofuran. When this reaction pathway is inhibited by sterically encumbering substituents on the benzofuran, no cyclopropanation of the furan ring is observed, and instead, double cyclopropanation of the benzene ring occurs. Double cyclopropanation of the benzene ring was also observed in reactions with indoles.

Journal Article↗

PubMed2005

Asymmetric intermolecular C-H functionalization of benzyl silyl ethers mediated by chiral auxiliary-based aryldiazoacetates and chiral dirhodium catalysts.

[reaction: see text] C-H functionalization of benzyl silyl ethers by means of rhodium-catalyzed insertions of aryldiazoacetates can be achieved in a highly diastereoselective and enantioselective manner by judicious choice of chiral catalyst or auxiliary. The dirhodium tetraprolinates such as Rh2((S)-DOSP)4 have been widely successful as chiral catalysts in the C-H functionalization chemistry of aryldiazoacetates, but give poor enantioselectivity in the reactions of aryldiazoacetates with benzyl silyl ether derivatives. The use of (S)-lactate as a chiral auxiliary resulted in C-H functionalization with moderately high diastereoselectivity (79-88% de) and enantioselectivity (68-85% ee). The best results (91-95% de, 95-98% ee), however, were achieved using Hashimoto's Rh2((S)-PTTL)4 catalyst.

Journal Article↗

PubMed2003

Development of a [3+3] cycloaddition strategy toward functionalized piperidines.

This paper describes a novel route to functionalized piperidines via a formal [3+3] cycloaddition reaction of activated aziridines and palladium-trimethylenemethane (Pd-TMM) complexes. The cycloaddition reaction generally proceeds enantiospecifically with ring opening at the least hindered site of the aziridine. Therefore, readily available enantiomerically pure 2-substituted aziridines can be utilized to prepare enantiomerically pure 2-substituted piperidines in good to excellent yield. The N-substituent on the aziridine proved to be crucial to the success of this reaction with only 4-toluenesulfonyl (Ts) and 4-methoxybenzenesulfonyl (PMBS) aziridines permitting smooth cycloaddition to take place. Additionally, spirocyclic aziridines have been found to participate in the [3+3] cycloaddition reaction, whereas 2,3-disubstituted aziridines can be applied to provide fused bicyclic piperidines, albeit in low yield.

Aziridines↗