Synthesis of Multisubstituted Allenes via Nickel-Catalyzed Cross-Electrophile Coupling

Abstract

In this context, we report the successful application of a cross-electrophile strategy in the synthesis of multisubstituted allenes. Under the catalysis of nickel, reductive cross-coupling between propargyl carbonates and organoiodides provides an entry to prepare tri- or tetrasubstituted allenes without employing any pregenerated organometallics. Furthermore, propargyl carbonates also prove to be suitable allenylating agents in nickel-catalyzed asymmetric reductive aryl-allenylation of aryl-iodide-tethered unactivated alkenes, furnishing a variety of chiral benzene-fused cyclic compounds bearing a quaternary allenyl-substituted stereogenic center in a highly enantioselective manner.

Recent Advances in Non-Precious Metal Catalysis

“…These strategies provide quick access to an array of alkyl, vinyl, and aryl halides of relevant structures to pharmaceutically interesting compounds. Other notable advances in Ni-catalyzed reactions include publications entitled (1) CgPhen-DalPhos enables the nickel-catalyzed O-arylation of tertiary alcohols with (hetero)­aryl electrophiles, (2) Synthesis of multisubstituted allenes via nickel-catalyzed cross-electrophile coupling, and (3) Nickel-catalyzed ring-opening allylation of cyclopropanols via homoenolate …”

Nickel-Catalyzed Reductive Coupling of γ-Metalated Ketones with Unactivated Alkyl Bromides

“…Nickel-catalyzed reductive coupling reactions are highly desirable, with the operational advantage of circumventing the use of preformed organometallic reagents of traditional cross-coupling reactions . These synthetically useful reductive processes have been widely developed by Gosmini, Weix, Gong, Reisman, Diao, Shu, Wang, and others using diverse electrophiles (Scheme a). A subset of such transformations includes nickel-catalyzed reductive coupling of enolizable intermediates, which have been demonstrated to be valuable in the synthesis of bioactive molecules .…”

Ni-Catalyzed Decarboxylative Silylation of Alkynyl Carbonates: Access to Chiral Allenes via Enantiospecific Conversions

“…Despite being distinct, for the latter category of propargylic substitutions several enantioselective protocols have evolved over the past decade . Of our particular interest is the demonstration of Ni-catalysis to forge chiral propargylic synthons with internal alkyne groups. ,, We recently reported the use of new propargylic surrogates based on alkyne-functionalized cyclic carbonates that under appropriate Cu-catalysis can be converted into silylated and borylated allenes . In both cases, there is a key β-O-elimination step that empowers the propargylic substitution process.…”

“…In both cases, there is a key β-O-elimination step that empowers the propargylic substitution process. However, carbometalation followed by β-O-elimination is unprecedented with Ni, while Ni-promoted propargylic silylation to our knowledge remains unknown despite the report of several successful Ni-catalyzed propargylic substitution processes using amine and carbon pronucleophiles (Scheme b). ,,, …”