β-Selective C(sp3)–H functionalization of alkyl boronates using photoredox catalysis

Alkyl boronates are a versatile class of organic molecules that have transformed chemical synthesis and had a broad impact in drug discovery, agrochemistry and materials research. For over 50 years, the conventional use of alkyl boronates has been the direct reaction of the C–B bond for the formation of C–C, C–N, C–O and C–X bonds. Here we report the use of alkyl boronates as directing groups to perform site-selective C(sp3)–H functionalization at the distal site. This methodology involves classic Lewis pair chemistry; it uses an alkyl-BF2, generated in situ from alkyl trifluoroborate salts, as a Lewis acid and 2-haloheteroarene as a Lewis base. Under mild photoredox reaction conditions, we are able to site-selectively functionalize the β-position of a wide range of alkyl trifluoroborate salts with the corresponding heteroarene through a cascade sequence of single-electron reduction, hydrogen atom transfer and intramolecular heteroaryl migration. This transformation effectively upgrades alkyl boron compounds into structurally complex heteroarene-containing building blocks. Alkyl boronates are typically involved in direct C–B bond transformations. Now the use of boronates as directing groups to enable β-selective C(sp3)–H functionalization is reported. The process uses Lewis pair chemistry between an in situ-generated alkyl BF2 and a 2-haloheteroarene, selectively forming β-heteroarylated alkyl boronates under photoredox conditions.