Enantioselective Giese Additions of Prochiral α-Amino Radicals.

Funder: Orionin Tutkimuss??ti?Funder: Emil Aaltosen S??ti?Funder: Royal SocietyFunder: AstraZenecaAmines featuring an adjacent stereocenter are important building blocks, and recent years have seen remarkable growth in methods forming these via prochiral α-amino radical intermediates. However, very few can exert control over the newly formed stereocenter. We disclose a strategy to overcome this in the context of one of the most widely used radical carbon-carbon bond forming reactions, the Giese reaction. Incorporation of a removable basic heteroarene into the substrate enables a network of attractive noncovalent interactions between a phosphoric acid catalyst, the subsequently formed α-amino radical, and the Giese acceptor, allowing the catalyst to exert control during the C-C bond forming step. Deprotection of the products leads to analogues of γ-aminobutyric acid. We anticipate that this strategy will be applicable to other asymmetric radical transformations in which catalyst control is presently challenging.ERC H2020, AstraZeneca, Royal Society, Isaac-Newton Trust, Orion Research Foundation sr (A.S.K.L) and Emil Aaltonen Foundatio

Hydrogen Atom Transfer Driven Enantioselective Minisci Reaction of Alcohols

Abstract: Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α‐amino radical coupling partners. We report a substantial evolution of the enantioselective Minisci reaction that enables α‐hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through the direct oxidative coupling of two C−H bonds on simple alcohol and pyridine partners through a hydrogen atom transfer (HAT)‐driven approach: a challenging process to achieve due to the numerous side reactions that can occur. Our approach is highly regioselective as well as highly enantioselective. Dicumyl peroxide, upon irradiation with 390 nm light, serves as both HAT reagent and oxidant whilst selectivity is controlled by use of a chiral phosphoric acid catalyst. Computational and experimental evidence provide mechanistic insight as to the origin of selectivity, revealing a stereodetermining deprotonation step distinct from the analogous reaction of amide‐containing substrates