Herein, we report a highly regio- and enantioselective copper-catalyzed reductive hydroxymethylation of styrenes and 1,3-dienes with 1 atm of CO. Diverse important chiral homobenzylic alcohols were readily prepared from styrenes. Moreover, a variety of 1,3-dienes also were converted to chiral homoallylic alcohols with high yields and excellent regio-, enantio-, and Z/E-selectivities. The utility of this transformation was demonstrated by a broad range of styrenes and 1,3-dienes, facile product modification, and synthesis of bioactive compounds (R)-(-)-curcumene and (S)-(+)-ibuprofen. Mechanistic studies demonstrated the carboxylation of phenylethylcopper complexes with CO as one key step.
Reported herein is a novel visible-light photoredox system with Pd(PPh ) as the sole catalyst for the realization of the first direct cross-coupling of C(sp )-H bonds in N-aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra- and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp )-C(sp ) and C(sp )-C(sp ) bonds in moderate to excellent yields. These redox-neutral reactions feature broad substrate scope (>60 examples), good functional-group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible-light photocatalyst and radicals are involved in the process.
Cross-electrophile couplings between two electrophiles are powerful and economic methods to generate C−C bonds in the presence of stoichiometric external reductants. Herein, we report a novel strategy to realize the first external-reductant-free cross-electrophile coupling via visible-light photoredox catalysis. A variety of tetraalkyl ammonium salts, bearing primary, secondary, and tertiary C−N bonds, undergo selective couplings with aldehydes/ketone and CO 2 . Notably, the in situ generated byproduct, trimethylamine, is efficiently utilized as the electron donor. Moreover, this protocol exhibits mild reaction conditions, low catalyst loading, broad substrate scope, good functional group tolerance, and facile scalability. Mechanistic studies indicate that benzyl radicals and anions might be generated as the key intermediates via photocatalysis, providing a new direction for cross-electrophile couplings.
Carboxylic acids, including amino acids (AAs), have been widely used as reagents for decarboxylative couplings. In contrast to previous decarboxylative couplings that release CO 2 as a waste byproduct, herein we report a novel strategy with simultaneous utilization of both the alkyl and carboxyl components from carboxylic acids. Under this unique strategy, carboxylic acids act as bifunctional reagents in the redox-neutral carbocarboxylation of alkenes. Diverse, inexpensive, and readily available α-AAs take part in such difunctionalizations of activated alkenes via visiblelight photoredox catalysis, affording a variety of valuable but otherwise difficult to access γ-aminobutyric acid derivatives (GABAs). Additionally, a series of dipeptides and tripeptides also participate in this photocatalytic carbocarboxylation. Although several challenges exist in this system due to the low concentration and quantitative amount of CO 2 , as well as unproductive side reactions such as hydrodecarboxylation of the carboxylic acids and hydroalkylation of the alkenes, excellent regioselectivity and moderate to high chemoselectivity are achieved. This process features low catalyst loading, mild reaction conditions, high step and atom economy, and good functional group tolerance, and it is readily scalable. The resulting products are subject to efficient derivations, and the overall process is amenable to applications in the latestage modification of complex compounds. Mechanistic studies indicate that a carbanion is generated catalytically and it acts as the key intermediate to react with CO 2 , which is also generated catalytically in situ and thus remains in low concentration. The overall transformation represents an efficient and sustainable system for organic synthesis, pharmaceutics, and biochemistry.
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