Photoredox/Cu‐Catalyzed Decarboxylative C(sp3)−C(sp3) Coupling to Access C(sp3)‐Rich gem‐Diborylalkanes

• Published in: Angewandte Chemie International Edition Vol. 63; no. 33; pp. e202401782 - n/a
• Main Authors: Huang, Mingming, Sun, Huaxing, Seufert, Florian, Friedrich, Alexandra, Marder, Todd B., Hu, Jiefeng
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 12.08.2024
• Edition: International ed. in English
• Subjects: boron; boronate; Carboxylic acids; Catalysis; Chemical synthesis; Complexity; Copper; Coupling (molecular); Cross coupling; Drug development; Esters; Natural products; photochemistry; radical; Steric hindrance; Substrates; boronate; Boron; Cross-coupling; radical; photochemistry
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202401782

gem‐Diborylalkanes are highly valuable building blocks in organic synthesis and pharmaceutical chemistry due to their ability to participate in multi‐step cross‐coupling transformations, allowing for the rapid generation of molecular complexity. While progress has been made in their synthetic metholodology, the construction of β‐tertiary and C(sp3)‐rich gem‐diborylalkanes remains a synthetic challenge due to substrate limitations and steric hindrance issues. An approach is presented that utilizes synergistic photoredox and copper catalysis to achieve efficient C(sp3)−C(sp3) cross‐coupling of alkyl N‐hydroxyphthalimide esters, which can easily be obtained from alkyl carboxylic acids, with diborylmethyl species, providing a series of C(sp3)‐rich gem‐diborylalkanes with 1°, 2°, and even 3° β positions. Furthermore, this approach can also be applied to complex medicinal compounds and natural products, offering rapid access to molecular complexity and late‐stage functionalization of C(sp3)‐rich drug candidates. Mechanistic experiments revealed that diborylmethyl Cu(I) species participated in both the photoredox process and the key C(sp3)−C(sp3) bond‐forming step. A mild and highly selective decarboxylative C(sp3)−C(sp3) cross‐coupling diborylmethylation of various alkyl carboxylic acids with a gem‐diboryl metallic reagent has been accomplished via dual photoredox/copper catalysis providing a series of C(sp3)‐rich gem‐diborylalkanes with 1°, 2°, and even 3° β positions.