Light-Initiated Hydrogen Atom Transfer-Driven Asymmetric Minisci Reaction of Primary Alcohols

Key words

photocatalysis - Minisci reaction - primary alcohols - pyridines - chiral phosphoric acids - hydrogen atom transfer

Significance

Ermanis, Phipps, and co-workers report a light-initiated, hydrogen atom transfer (HAT)-driven asymmetric Minisci reaction of primary alcohols with pyridines. The reaction proceeds through an α-hydroxy radical intermediate formed by α-hydrogen atom abstraction from the alcohol by dicumyl peroxide (DCP) upon irradiation. The resulting hydroxyalkylated pyridines are obtained in moderate yields and with good to excellent enantio­selectivities. The reaction is selective to the C2 position of the pyridine and tolerates alkyl functionalization on every position of the pyridine, as well as a variety of functional handles on the primary alcohol.

Comment

The currently reported formal dehydrogenative C–H to C–H bond coupling expands upon the authors’ previously reported Minisci reaction between N-heterocycles and α-imido radicals generated in situ (Science 2018, 360, 419) by eliminating the requirement for a protected amine to form the α-radical. The addition of unprotected feedstock alcohols to the scope of this type of reactivity presents a significant advance in its utility. We look forward to potential modifications of this methodology that would optimize the yield.

Publication History

Article published online:
18 July 2022