Synthesis of Homoallylamines Enabled by Cobalt or Palladium Catalyzed Allylic Substitution of Azaarylmethylamines.

Pd(OAc)2/Nixantphos or CoI2/Nixantphos catalyzed allylic substitutions with weakly acidic C(sp)3-H bonds of azaarylmethylamines are described. This method facilitates access to various kinds of heteroaryl rings containing homoallylamines (39 examples, 30-98% yields) with excellent functional group tolerance and diastereoselectivity. Compared with the Pd/Nixantphos complex, the Co/Nixantphos catalysis could obtain the cyclic products with good to excellent diastereoselectivities. Importantly, the CoI2/(R,R)-Me-Duphos catalyzed reactions exhibit moderate enantioselectivity. Additionally, the scalability of this transformation is successfully demonstrated.

Nickel-Catalyzed Reductive Arylation of α-Bromo Sulfoxide.

A nickel-catalyzed cross-electrophile coupling of aryl iodides with α-bromo sulfoxide to access a diverse array of aryl benzyl sulfoxides has been discovered. These reactions occurred under mild conditions with excellent functional group tolerance so that optically enriched sulfoxides could be coupled with aryl iodides, generating corresponding sulfoxides with excellent stereochemical integrity. Furthermore, the scalability of this transformation was demonstrated. Initial mechanistic studies revealed that the reaction undergoes a radical pathway.

Nickel/photoredox-catalyzed enantioselective arylation of α-chloro thioesters.

The first dual nickel/photoredox-catalyzed enantioselective reductive cross-coupling of racemic α-chloro thioesters with aryl iodides has been developed. This strategy avoids the need for organometallic reagents or stoichiometric metal reductants. This reaction could tolerate a wide range of substrate scope with excellent reactivity and high enantioselectivities (up to 91% ee) to access a variety of chiral α-aryl thioesters. The synthetic utility of the corresponding α-aryl thioesters is demonstrated. Furthermore, we explored the mechanism of such an enantioselective radical cross-coupling process.

Nickel-Catalyzed Cross-Electrophile Coupling of 1,2,3-Benzotriazin-4(3H)-ones with Aryl Bromides.

The nickel-catalyzed cross-electrophile coupling of 1,2,3-benzotriazin-4(3H)-ones with aryl bromides to generate a diverse array of ortho-arylated benzamide derivatives has been developed. The reaction displayed good functional group tolerance with Zn as the reductant. The key to this transformation is the ring opening of benzotriazinones, which undergo a denitrogenative process to obtain various benzamide derivatives (29 examples, 42-93% yield). The scalability of this transformation was demonstrated.

Nickel/Photoredox-Catalyzed Enantioselective Reductive Cross-Coupling between Vinyl Bromides and Benzyl Chlorides.

A visible-light-promoted nickel/photoredox-catalyzed reductive cross-coupling reaction between vinyl bromides and benzyl chlorides is reported. A diverse array of enantioenriched allylic centers containing products could be achieved in good yields (up to 90%) and high enantioselectivities (up to 95% ee). The mechanistic studies show that this reductive cross-coupling involves a radical pathway.

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

A nickel-catalyzed reductive cross-coupling reaction of aryl cyclopropyl ketones with easily accessible unactivated alkyl bromides to access aryl alkyl ketones has been developed. This strategy facilitates access to various of γ-alkyl-substituted ketones via ring opening of cyclopropyl ketones (26 examples, 50-90% yield). Initial mechanistic studies revealed that the reaction proceeds via radical cleavage of the alkyl bromide.

Palladium-Catalyzed Direct Arylation of 2-Pyridylmethyl Silanes with Aryl Bromides.

The first palladium-catalyzed direct arylation of 2-pyridylmethyl silanes with aryl bromides to generate a diverse array of aryl(2-pyridyl)-methyl silane derivatives has been developed. This protocol facilitates access to various kinds of heterocycle-containing silanes in good to excellent yields (40 examples, 66-97% yield) with good functional group tolerance. The scalability of this transformation is demonstrated.

Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides.

The catalytic generation of homoenolates and their higher homologues has been a long-standing challenge. Like the generation of transition metal enolates, which have been used to great affect in synthesis and medicinal chemistries, homoenolates and their higher homologues have much potential, albeit largely unrealized. Herein, a nickel-catalyzed generation of homoenolates, and their higher homologues, via decarbonylation of readily available cyclic anhydrides has been developed. The utility of nickel-bound homoenolates and their higher homologues is demonstrated by cross-coupling with unactivated alkyl bromides, generating a diverse array of aliphatic acids. A broad range of functional groups is tolerated. Preliminary mechanistic studies demonstrate that: (1) oxidative addition of anhydrides by the catalyst is faster than oxidative addition of alkyl bromides; (2) nickel bound metallocycles are involved in this transformation and (3) the catalyst undergoes a single electron transfer (SET) process with the alkyl bromide.

Nickel-Catalyzed Desymmetrizing Cross-Electrophile Coupling of Cyclic Meso-Anhydrides.

A Ni-catalyzed desymmetrizing cross-electrophile coupling of cyclic meso-anhydrides with aryl triflates has been successfully demonstrated. This is the only example using cyclic meso-anhydrides in cross-electrophile coupling reactions. A diverse array of valuable γ-keto acid building blocks can be generated under these conditions with excellent functional group tolerance and stereochemical fidelity.