Effective 1,5-, 1,6- and 1,7-remote stereocontrol in reactions of alkoxy- and hydroxy-substituted allylstannanes with aldehydes.

Alk-2-enylstannanes with 4-, 5- and 6-alkoxy- or -hydroxy-substituents are transmetallated stereoselectively with tin(iv) halides to generate allyltin trihalides which react with aldehydes to give (Z)-alk-3-enols with useful levels of 1,5-, 1,6- and 1,7-stereocontrol. Alk-2-enylstannanes with a stereogenic centre bearing a hydroxy or alkoxy group at the 4-, 5- or 6-position, react with overall (Z)-1,5-, 1,6- and 1,7-syn-stereoselectivity with respect to the hydroxy and alkoxy substituents. The analogous reactions of alkoxy- and -hydroxyalk-2-enylstannanes with a methyl bearing stereogenic centre at the 4- or 5-position react with overall (Z)-1,5- and 1,6-anti-stereoselectivity with respect to the hydroxy and methyl substituents.

Analysis of the reactions used for the preparation of drug candidate molecules.

The purpose of this perspective is to indicate the range of chemistries used in the manufacture of drug candidate molecules and to highlight certain gaps in current technologies. To do this a survey was carried out of chemical syntheses within the Process Chemistry R&D departments of GlaxoSmithKline, AstraZeneca and Pfizer.