The development of an intermolecular and enantioselective aza-Wacker reaction is described. Using indoles as the N-source, a selection of alkenols as the coupling partner enables selective β-hydride elimination towards the alcohol. This strategy preserves the newly formed stereocenter by preventing the formation of traditionally observed enamine products. Allylic and homoallylic alcohols with a variety of functional groups are compatible with the reaction in high enantioselectivity. Isotopic-labeling experiments support a syn amino-palladation mechanism for this new class of aza-Wacker reactions.

Herein we describe the development of a Pd-catalyzed enantioselective Markovnikov addition of carbamates to allylic alcohols for the construction of α-tertiary and α-secondary amines. The reaction affords a range of β-amino alcohols, after reduction of the aldehyde in situ, which contain a variety of functional groups in moderate yields and moderate to good enantioselectivities. These products can be readily oxidized to β-amino acids, valuable building blocks for the synthesis of biologically active compounds. Mechanistic studies indicate that C–N bond formation occurs via a syn amino-palladation mechanism, an insight which may guide future reaction development given the limited number of enantioselective syntheses of α-tertiary amines.

It has come to our attention that there is an error in Scheme 2 regarding the labeling of compounds syn-3y and anti-3y. The corrected graphic is shown below. Scheme 2. Mechanistic Experiments