Despite a well-developed and growing body of work in copper catalysis, the potential of copper to serve as a photocatalyst remains underexplored. Herein, we describe a photoinduced, copper-catalyzed method for coupling readily available racemic tertiary alkyl chloride electrophiles with amines to generate fully substituted stereocenters with high enantioselectivity. The reaction proceeds at –40 °C under excitation by a blue light-emitting diode and benefits from the use of a single, Earth-abundant transition metal acting as both the photocatalyst and the source of asymmetric induction. An enantioconvergent mechanism transforms the racemic starting material into a single product enantiomer.
Overarching
principles for salting-out extraction are long-established
but poorly disseminated. We highlight the opportunity for more widespread
application of this technique using the Hofmeister series as a foundational
basis for choosing the right salt. The power of this approach is exemplified
by the aqueous workup of a highly water-soluble nucleoside in which
the use of sodium sulfate allowed for high recoveries without relying
on back extraction.
The first Suzuki cross-couplings of unactivated tertiary alkyl electrophiles are described, employing a readily accessible catalyst (NiBr2·-diglyme/4,4′-di-t-butyl-2,2′-bipyridine, both commercially available); this also represents the initial example of the use of a Group 10 catalyst to cross-couple unactivated tertiary electrophiles to form carbon–carbon bonds. This approach to the synthesis of all-carbon quaternary carbon centers does not suffer from isomerization of the alkyl group, in contrast with the umpolung strategy for this bond construction (cross-coupling a tertiary alkylmetal with an aryl electrophile). Preliminary mechanistic studies are consistent with the generation of a radical intermediate along the reaction pathway.
A modular Cu/ABNO catalyst system has been identified that enables efficient aerobic oxidative coupling of alcohols and amines to amides. All four permutations of benzylic/aliphatic alcohols and primary/secondary amines are viable in this reaction, enabling broad access to secondary and tertiary amides. The reactions exhibit excellent functional group compatibility and are complete within 30 min – 3 h at room temperature. All components of the catalyst system are commercially available.
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