Practical and Modular Construction of C(sp(3))-Rich Alkyl Boron Compounds

• Published in: Journal of the American Chemical Society Vol. 143; no. 1; pp. 471 - 480
• Main Authors: Yang, Yangyang, Tsien, Jet, Ben David, Ayala, Hughes, Jonathan M. E., Merchant, Rohan R., Qin, Tian
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 13.01.2021
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; ALKENYLBORONIC ACIDS; CROSS-COUPLING REACTIONS; ESTERS; SECONDARY; CARBONYL-COMPOUNDS; DIAZO-COMPOUNDS; CATALYZED BORYLATION; HOMOLOGATION; DERIVATIVES; N-TOSYLHYDRAZONES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c11964

Alkyl boronic acids and esters play an important role in the synthesis of C(sp(3))-rich medicines, agrochemicals, and material chemistry. This work describes a new type of transition-metal-free mediated transformation to enable the construction of C(sp(3))-rich and sterically hindered alkyl boron reagents in a practical and modular manner. The broad generality and functional group tolerance of this method is extensively examined through a variety of substrates, including synthesis and late-stage functionalization of scaffolds relevant to medicinal chemistry. The strategic significance of this approach, with alkyl boronic acids as linchpins, is demonstrated through various downstream functionalizations of the alkyl boron compounds. This two-step concurrent cross-coupling approach, resembling formal and flexible alkyl-alkyl couplings, provides a general entry to synthetically challenging high Fsp(3)-containing drug-like scaffolds.