Narasaka–Prasad reduction

The Narasaka–Prasad reduction, sometimes simply called Narasaka reduction, is a diastereoselective reduction of β-hydroxy ketones to the corresponding syn-dialcohols. The reaction employs a boron chelating agent, such as BBu₂OMe, and a reducing agent, commonly sodium borohydride. This protocol was first discovered by Narasaka in 1984.[1]

Scheme for the Narasaka–Prasad reduction

The reaction proceeds through the 6-membered transition state shown below. Chelation by the boron agent favors hydride delivery from the top face because it leads directly to the more stable chair-like conformation of the product (Fürst-Plattner Rule). The intermolecular hydride delivery from NaBH₄ therefore proceeds via an axial attack from the opposite face with respect to the existing alcohol.[1]

Transition state for the Narasaka–Prasad reduction showing the reasons for the observed diastereoselectivity

This reaction can be contrasted with the similar Evans–Saksena reduction that employs a different boron reagent in order to achieve intramolecular hydride delivery from the same face of the alcohol, thus producing the anti-diol.

The Narasaka–Prasad reduction has been employed in many total syntheses in the literature,[2] such as discodermolide[3]