Copper-catalyzed enantioselective decarboxylative cyanation of β,γ-unsaturated carboxylic acids to access chiral allyl nitriles

Copper-Catalyzed Enantioselective Decarboxylative Cyanation of Benzylic Acids Promoted by Hypervalent Iodine(III) Reagents

“…Based on the above mechanistic experiments and existing related literature, 7,[10][11][12]16 Finally, a linear correlation between the enantiopurity of the product 2a with that of ligand L1 suggested that a monomeric copper complex with a single chiral ligand was involved in the enantio-determining transition state.…”

“…6 However, this strategy remains largely elusive in hypervalent-iodine(III)reagent-mediated asymmetric decarboxylative radical transformation. 7 On the other hand, optically pure alkyl nitriles are key structural elements in a diverse range of bioactive natural products, pharmaceuticals, and agrochemicals, and they are also recognized as versatile synthetic intermediates for the synthesis of various chiral aldehydes, ketones, amides, amines, acids, and heterocycles. 8 Not surprisingly, great efforts have been devoted to synthesize α-chiral nitriles under mild conditions using simple and inexpensive chemical materials.…”

“…12a Very recently, our group developed a copper-catalyzed enantioselective decarboxylative cyanation of β,γ-unsaturated carboxylic acids by in situ activation of acids using a hypervalent iodine(III) reagent. 7 During the preparation of this manuscript, Xu, Zhang, and Fu independently developed a photoelectrocatalytic strategy for the copper-catalyzed asymmetric decarboxylative cyanation of benzylic acids, which is typically conducted in photo-and electrochemical reactors. 13 Herein, we report a coppercatalyzed direct and enantioselective decarboxylative cyanation of simple benzylic acids, which was promoted by a hypervalent iodine(III) reagent (Scheme 1c).…”

“…Under simple operation and mild conditions, the commercially inexpensive hypervalent iodine(III) reagent covalently in situ activated readily available carboxylic acids, producing alkyl radicals without prefunctionalization. Inspired by our previous work, 7 the present study began with exploration of the reaction between phenylpropanoic acids (1a) and TMSCN (Table 1; see Tables S1−S7 in the Supporting Information for more detail). To our delight, with a catalytic system comprising CuF 2 (10 mol %), chiral bisoxazoline ligand L1 (15 mol %), hypervalent iodine(III) reagent (PhI�O, 2.0 equiv), and K 2 HPO 4 •3H 2 O (1.5 equiv), the decarboxylative cyanation reaction proceeded smoothly in acetone at 30 °C, affording the desired cyanide product 2a in 66% yield with 96:4 er (entry 1).…”

Cu-catalyzed enantioselective decarboxylative cyanation via the synergistic merger of photocatalysis and electrochemistry

“…This approach is particularly useful in enantioselective carbon–carbon bond-forming reactions with electrophilic organohalides via a redox-neutral strategy. 7 e ,7 f However, enantioselective decarboxylative carbon-heteroatom bond-formation reactions always require an oxidizing agent, 8 or the prefunctionalization of the carboxylic acids 9 to facilitate the decarboxylative generation of alkyl radical via single electron reduction of carboxylic acid derivatives, such as redox-active esters. 4 a ,7 a Seminal work by G. Liu and coworkers has demonstrated the enantioselective cyanation of redox-active esters by Ir photoredox catalysis and Cu catalysis.…”