Iridium-catalysed enantioselective formal deoxygenation of racemic alcohols via asymmetric hydrogenation

Asymmetric hydrogenation of alkenes is one of the most powerful tools for the preparation of optically active compounds. However, to achieve high enantioselectivity, the starting olefin in most cases needs to be isomerically pure in either the cis or the trans form. Generally, most olefination protocols provide olefins as isomeric mixtures that are difficult to separate, and in many cases also generate lots of waste. In contrast, the synthesis of racemic alcohols is straightforward and highly atom-efficient, with products that are easier to purify. Here, we describe a strategy that enables rapid access to chiral alkanes via enantioconvergent formal deoxygenation of racemic alcohols. Mechanistic studies indicate an Ir-mediated elimination of water and subsequent in situ hydrogenation. This approach allows rapid and efficient assembly of chiral intermediates and is exemplified in the total synthesis of antidepressant sertraline and sigma(2) receptor PB 28.