Cobalt‐Catalyzed Enantioselective Negishi Cross‐Coupling of Racemic α‐Bromo Esters with Arylzincs

Abstract

The first cobalt-catalyzed enantioselective Negishi cross-coupling reaction, and the first arylation of α-halo esters with arylzinc halides, are disclosed. Employing a cobalt-bisoxazoline catalyst, various α-arylalkanoic esters were synthesized in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield). A diverse range of functional groups, including ether, halide, thioether, silyl, amine, ester, acetal, amide, olefin and heteroaromatics is tolerated by this method. This method was suitable for gram-scale reactions, enabling the synthesis of (R)-xanthorrhizol with high enantiopurity. Radical clock experiments support the intermediacy of radicals.

Enantioselective synthesis of (R)‐Cinacalcet via cobalt‐catalysed asymmetric Negishi cross‐coupling

“…The gram‐scale synthesis of a reaction exhibits its potential of practical application . Although racemic 4‐methoxybenzyl 2‐bromopropanoate 3 could couple with 1‐naphthalenylzinc bromide 2 on a o.5 mmol scale in our previous research, it is noteworthy to scale this enantioselective cross‐coupling to gram scale. To our pleasure, a gram‐scale cobalt‐catalysed cross‐coupling of ester 3 with arylzinc reagent 2 was successfully developed without the erosion of yield and ee.…”

“…Moreover, the inexpensive and lower toxicity of cobalt has led to a significant progress on cobalt‐catalysed Negishi cross‐coupling reactions . Recently, we have developed the first cobalt‐catalysed enantioselective Negishi cross‐coupling to construct the stereogenic benzylmethyl center directly . Herein, we disclosed an expanded application of this methodology to an asymmetric synthesis of ( R )‐cinacalcet via a gram‐scale cobalt‐catalysed asymmetric cross‐coupling of racemic ester with arylzinc reagent.…”

Enantioselective Palladium‐Catalyzed Cross‐Coupling of α‐Bromo Carboxamides and Aryl Boronic Acids

“…Thea symmetric cross-coupling of a-halo carbonyl compounds and aryl metal reagents is an attractive method for preparing chiral a-aryl carbonyl compounds from simple and readily available starting materials. [2] In previous excellent work, the groups of Fu, [3] Zhong and Bian, [4] and Nakamura [5] developed af ew enantioselective versions with chiral Ni, Co,a nd Fe catalysts (Scheme 1a), albeit with high catalyst loadings (mostly > 5mol %). An asymmetric crosscoupling with stable and readily available aryl boronic acids as coupling partners with ap alladium catalyst at al ower catalyst loading is attractive and yet to be realized.…”

Nickel/Photoredox‐Catalyzed Asymmetric Reductive Cross‐Coupling of Racemic α‐Chloro Esters with Aryl Iodides

“…Herein, we employ an organic photoredox catalyst with Hantzsch ester (HEH) as the terminal organic reductant to realize the nickel catalyzed asymmetric reductive cross‐coupling of α‐chloro esters with aryl iodides to furnish α‐aryl esters (Scheme D). This method represents an advance over prior methods that employed prefunctionalized aryl coupling partners (organosilane, Grignard, or organozinc reagents), or preformed enolates . It is also an alternative strategy for the enantioselective formation of C(sp 2 )−C(sp 3 ) bonds to the use of stoichiometric metal as reductant.…”