Copper-Mediated Dehydrogenative C(sp³)–H Borylation of Alkanes

Abstract

Borylations of inert carbon–hydrogen bonds are highly useful for transforming feedstock chemicals into versatile organoboron reagents. Catalysis of these reactions has historically relied on precious-metal complexes, which promote dehydrogenative borylations with diboron reagents under oxidant-free conditions. Recently, photoinduced radical-mediated borylations involving hydrogen atom transfer pathways have emerged as attractive alternatives because they provide complimentary regioselectivities and proceed under metal-free conditions. However, these net oxidative processes require stoichiometric oxidants and therefore cannot compete with the high atom economy of their precious-metal-catalyzed counterparts. Herein, we report that CuCl2 catalyzes radical-mediated, dehydrogenative C­(sp3)–H borylations of alkanes with bis­(catecholato)­diboron under oxidant-free conditions. This is a result of an unexpected dual role of the copper catalyst, which promotes oxidation of the diboron reagent to generate an electrophilic bis-boryloxide that acts as an effective borylating agent in subsequent redox-neutral photocatalytic C–H borylations.

Terminal C(sp 3 )–H borylation through intermolecular radical sampling

“…By increasing the amount of inexpensive and easily recyclable hexane to 20 equiv, we achieved a 55% isolated yield of hexyl 2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine (Bdan) ( 1′ , treated with 1,8-diaminonaphthalene 3instead of pinacol) with no loss of regioselectivity (entry 10). This success led to the regioselective C(sp 3 )–H borylation of unbranched alkanes under gentle photocatalytic conditions, a result previously unachievable without our sulfoxide-controlled photocatalytic procedure ( 43 – 45 ).…”

“…However, achieving selective modification of simple alkanes, particularly the terminal functionalization of unbranched chains, poses a formidable challenge owing to the formation of relatively unstable primary carbon radical intermediates through HAT from stronger C–H bonds (Fig. 1B) ( 19 – 21 , 27 , 37 , 38 , 42 – 45 ).…”

“…Nonetheless, the system exhibited unsatisfactory regioselectivity when applied to straight-chain substrates, such as pentane, resulting in an approximately 1:1 methyl to methylene ratio. Very recently, the Xia group ( 44 ) and Aggarwal group ( 45 ) independently reported intriguing C(sp 3 )–H borylation reactions that use base metal chlorides under light irradiation. The regioselectivity observed was similar to that of Aggarwal and Noble’s former metal-free work ( 43 ), thereby confirming the challenge of achieving selective borylation of unbranched alkanes.…”

Cu(ii) salts as terminal oxidants in visible-light photochemical oxidation reactions

“…28 It is possible that another species may be acting as the terminal oxidant in this transformation; Aggarwal published a C–H borylation reaction under similar reaction conditions and observed the copper-catalyzed in situ formation of O(Bcat) 2 with residual water. 29 This oxidation of B 2 cat 2 is balanced by the reduction of the water to molecular hydrogen, allowing the C–H borylation to proceed with catalytic CuCl 2 .…”

Copper-Catalyzed Synthesis of N-Fused Quinolines via C(sp3)–H Activation-Radical Addition–Cyclization Cascade

“…However, the application of such C–H bond functionalization in constructing structurally diverse polyheterocycles is rare . Besides, while transition-metal-catalyzed C­(sp 3 )–H functionalization reactions with noble metals were widely used, the application of inexpensive metals, such as copper or iron, remains limited and is still challenging . Therefore, it is significant to develop novel catalytic systems for C­(sp 3 )–H bond activation toward structurally interesting molecules.…”