Ni-Catalyzed Formal Cross-Electrophile Coupling of Alcohols with Aryl Halides

Abstract

Direct coupling of unactivated alcohols remains a challenge in current synthetic chemistry. We herein demonstrate a strategy building upon in situ halogenation/reductive coupling of alcohols with aryl halides to forge Csp2–Csp3 bonds. The combination of 2-chloro-3-ethylbenzo­[d]­oxazol-3-ium salt (CEBO) and TBAB as the mild bromination reagents enables rapid transformation of a wide range of alcohols to their bromide counterparts within one to 5 min in CH3CN and DMF, which is compatible with the Ni-catalyzed cross-electrophile coupling conditions in the presence of a chemical reductant. The present method is suitable for arylation of a myriad of structurally complex alcohols with no need for prepreparation of alkyl halides. More importantly, the mild and kinetically rapid bromination process has shown good selectivity in the bromination/arylation of symmetric diols and less sterically hindered hydroxyl groups in polyols, thus offering promise for selective functionalization of diols and polyols without laborious protecting/deprotecting operations. The practicality of this work is also evident in the arylation of a number of carbohydrates, drug compounds, and naturally occurring alcohols.

Recent Progress on Transition-Metal-Mediated Reductive C(sp3)–O Bond Radical Addition and Coupling Reactions

“…Gong demonstrated a strategy of in situ halogenation/reductive coupling of alkyl alcohols with aryl halides (Scheme 34). 71 They found that the mixture of 2-chloro-3-ethylbenzo[d]oxazol-3-ium salt (CEBO) and TBAX (X = B or C) enabled rapid transformation of a wide range of alcohols into their halide counterparts within 1 to 5 min in CH3CN and DMF at room temperature, which is compatible with the Ni-catalyzed cross-electrophile coupling conditions. 3-Ethylbenzo[d]oxazol-2(3H)-one (BEO), as a coproduct of halogenation step, served as an important additive.…”

“…Gong has demonstrated a strategy that involves in situ halogenation/reductive coupling of alkyl alcohols with aryl halides (Scheme 34). 71…”

Radical Deoxyfunctionalisation Strategies**

“…One method involves the in situ conversion of the hydroxyl motif into the corresponding iodide or bromide, which subsequently reacts via metal‐catalysed coupling in a one‐pot cascade strategy. Inspired by this concept, Gong [47] and Weix [48] concurrently reported Ni‐catalysed methodologies for the formal cross‐coupling of alcohols with aryl halides (Gong) and aryl/alkenyl halides (Weix) (Scheme 29). The former employed 2‐chloro‐3‐ethylbenzo[ d ]‐oxazol‐3‐ium salts (CEBO) 61 as in situ halogenating reagents, while the latter utilised Hendrickson's POP reagent 62 [49] to achieve this goal.…”

Radical Deoxyfunctionalisation Strategies

“…One method involves the in situ conversion of the hydroxyl motif into the corresponding iodide or bromide, which subsequently reacts via metal-catalysed coupling in a one-pot cascade strategy. Inspired by this concept, Gong [41] and Weix [42] concurrently reported Ni-catalysed methodologies for the formal crosscoupling of alcohols with aryl halides (Gong) and aryl/alkenyl halides (Weix) (Scheme 23). The former employed 2-chloro-3ethylbenzo[d]-oxazol-3-ium salts (CEBO) 34 as in situ halogenating reagents, while the latter utilised Hendrickson's POP reagent 35 [43] to achieve this goal.…”