Abstract
By employing an N-heterocyclic carbene (NHC) catalyst, we developed a versatile catalytic system that enables deaminative cross-coupling reactions of aldehydes with redox-active pyridinium salts. Katritzky pyridinium salts behave as single-electron oxidants capable of generating alkyl radicals enabled by the redox properties of the enolate form of Breslow intermediates. The resultant alkyl radical undergoes efficient recombination with the NHC-bound aldehyde-derived carbonyl carbon radical for the formation of a C–C bond. The mild and transition metal-free reaction conditions tolerate a broad range of functional groups, and its utility has been further demonstrated by the modification of a series of peptide feedstocks and application to the three-component dicarbofunctionalization of olefins.
Highlights
The utilization of widely available and naturally abundant functionalities is of great interest because it promises a convenient and cost-effective synthetic method to enable the rapid modi cation of an important class of feedstocks. a-Amino acids and their derivatives are prevalent structural motifs across natural products[1] and medicinally relevant compounds,[2] and the development of a general method to exploit them as synthetic intermediates is highly desirable for rapid modi cation and generation of new chemical entities with broad utility
As outlined in Scheme 1d, we imagined that the alkyl radical generated by the single electron transfer (SET) pathway could be combined with the oxidized enolate form of the Breslow intermediate, which would present a new opportunity for the rapid modi cation of a series of amino acid-derived and peptidic compounds
To further highlight the broad applicability of this reaction, we investigated whether the current N-heterocyclic carbene (NHC) catalysis enables the vicinal alkyl carbofunctionalization of alkenes through a radical relay mechanism involving a SET from the enolate form and radical addition of the resultant alkyl radical to an alkene followed by radical–radical coupling
Summary
The utilization of widely available and naturally abundant functionalities is of great interest because it promises a convenient and cost-effective synthetic method to enable the rapid modi cation of an important class of feedstocks. a-Amino acids and their derivatives are prevalent structural motifs across natural products[1] and medicinally relevant compounds,[2] and the development of a general method to exploit them as synthetic intermediates is highly desirable for rapid modi cation and generation of new chemical entities with broad utility. A-Amino acids and their derivatives are prevalent structural motifs across natural products[1] and medicinally relevant compounds,[2] and the development of a general method to exploit them as synthetic intermediates is highly desirable for rapid modi cation and generation of new chemical entities with broad utility.
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