Nickel‐Catalyzed Regioselective Hydroalkylation and Hydroarylation of Alkenyl Boronic Esters

Abstract

Metal hydride catalyzedhydrocarbonation reactions of alkenes are an efficient approach to construct new carboncarbon bonds from readily available alkenes.H owever,t he regioselectivity of hydrocarbonation remains challenging to be controlled. In nickel hydride (NiH) catalyzedh ydrocarbonation, linear selectivity is most often obtained because of the relative stability of the linear Ni-alkyli ntermediate over its branched counterpart. Herein, we showt hat the boronic pinacol ester (Bpin) group directs aNi-catalyzed hydrocarbonation to occur at its adjacent carbon center,resulting in formal branch selectivity.B oth alkyla nd aryl halides can be used as electrophiles in this hydrocarbonation, providing access to aw ide range of secondary alkylB pin derivatives,w hich are valuable building blocks in synthetic chemistry.T he utility of the method is demonstrated by the late-stage functionalization of natural products and drug molecules,t he synthesis of an anticancer agent, and iterative syntheses.

Enantioselective access to chiral aliphatic amines and alcohols via Ni-catalyzed hydroalkylations

“…Mechanistic consideration. Then, we carried out the reaction using deuterated silane (Ph 2 SiD 2 ) 32 under otherwise identical to standard conditions (Fig. 6).…”

“…Based on the mechanistic results and literature precedence [28][29][30][31][32][33][34][42][43][44][45]48,49 , two tentative mechanistic pathways are proposed and depicted in Fig. 7.…”

“…Buchwald developed a seminal work on Cu-H-catalyzed hydroamination of internal alkenes to achieve chiral dialkyl amines 26,27 . In 2016, Fu group reported a pioneer work on Ni-H-catalyzed racemic hydrofunctionalizations of alkenes with aryl or alkyl halides 28 , which have become a promising alternative for traditional asymmetric C-C cross-coupling reaction to construct saturated stereogenic carbon centers [28][29][30][31][32][33][34][35] . The use of readily available and bench-stable alkenes as a masked nucleophile in the presence of silane circumvents the use of stoichiometric and often sensitive organometallic reagents, which usually require time-consuming preformation 36,37 .…”

Regio‐ and Enantioselective Ni‐Catalyzed Formal Hydroalkylation, Hydrobenzylation, and Hydropropargylation of Acrylamides to α‐Tertiary Amides

“…This outcome suggests the Ni‐catalyzed Csp3–Csp3 cross‐coupling step is facilitated by the assistance of amide group. Next, we carried out the reaction using deuterated silane (PhSiD 2 ) [7e] under otherwise identical to standard conditions [Eq. (3)].…”

Nickel-Catalyzed Electronically Reversed Enantioselective Hydrocarbofunctionalizations of Acrylamides

“…This result suggested that the presence of an amide group is essential for the Ni-catalyzed C(sp 3 )-C(sp 3 ) bond-forming step. Next, the reaction was conducted by using a deuterated silane (Ph 2 SiD 2 ) 12 under otherwise standard conditions (Scheme 4b). The desired hydroalkylation product 7 was obtained in 43% yield with 91% ee, along with the hydrogenation product 8 in 55% yield.…”