Streamlined Alkylation via Nickel-Hydride-Catalyzed Hydrocarbonation of Alkenes.

Compounds rich in sp-hybridized carbons are desirable in drug discovery. Nickel-catalyzed hydrocarbonation of alkenes is a potentially efficient method to synthesize these compounds. By using abundant, readily available, and stable alkenes as pro-nucleophiles, these reactions can have broad scope and high functional group tolerance.

Copper-Catalyzed Intermolecular Functionalization of Unactivated C(sp)-H Bonds and Aliphatic Carboxylic Acids.

Intermolecular functionalization of C(sp)-H bonds and aliphatic carboxylic acids enables the efficient synthesis of high value-added organic compounds from readily available starting materials. Although methods involving hydrogen atom transfer have been developed for such functionalization, these methods either work for only activated C(sp)-H bonds or bring in a narrow set of functional groups. Here we describe a Cu-catalyzed process for the diverse functionalization of both unactivated C(sp)-H bonds and aliphatic carboxylic acids.

Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enecarbamates.

Chiral alkyl amines are omnipresent as bioactive molecules and synthetic intermediates. The catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enecarbamates (-Cbz-protected enamines) and alkyl halides with high regio- and enantioselectivity.

Enantioselective C(sp)-C(sp) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis.

Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp-hybridized carbon centres, which are attractive candidate compounds in drug discovery. Enantioselective C(sp)-C(sp) coupling is challenging, especially of alkyl electrophiles without an activating group (aryl, vinyl, carbonyl). Here, we report a strategy based on nickel hydride addition to internal olefins followed by nickel-catalysed alkyl-alkyl coupling.

Deoxygenative trifluoromethylthiolation of carboxylic acids.

Here we describe a deoxygenative trifluoromethylthiolation method that yields trifluoromethyl thioesters from readily available carboxylic acids. The method is built upon an "umpolung" strategy where triphenylphosphine is used to first activate an electrophilic trifluoromethylthiolating reagent and then serves as an oxygen acceptor for the deoxygenation. The method is mild, efficient, broad-scope, and tolerant.

Nickel-Catalyzed Regioselective Hydroalkylation and Hydroarylation of Alkenyl Boronic Esters.

Metal hydride catalyzed hydrocarbonation reactions of alkenes are an efficient approach to construct new carbon-carbon bonds from readily available alkenes. However, the regioselectivity of hydrocarbonation remains challenging to be controlled. In nickel hydride (NiH) catalyzed hydrocarbonation, linear selectivity is most often obtained because of the relative stability of the linear Ni-alkyl intermediate over its branched counterpart.

Oxidative N-Heterocyclic Carbene Catalyzed Dearomatization of Indoles to Spirocyclic Indolenines with a Quaternary Carbon Stereocenter.

An efficient method for the asymmetric intramolecular dearomatization of indoles by using oxidative N-heterocyclic carbene catalysis is demonstrated. Valuable optically active spirocyclic indolenines bearing an all-carbon quaternary stereocenter are obtained in excellent yields and with excellent enantioselectivity. The starting indoles are readily prepared and the reactions proceed through an intramolecular indole 3-acylation with an in situ generated acyl azolium intermediate to form a spirocyclic ketone moiety.

Exploring Cooperative Effects in Oxidative NHC Catalysis: Regioselective Acylation of Carbohydrates.

The utility of oxidative NHC catalysis for both the regioselective and chemoselective functionalization of carbohydrates is explored. Chiral NHCs allow for the highly regioselective oxidative esterification of various carbohydrates using aldehydes as acylation precursors. The transformation was also shown to be amenable to both cis/trans diol isomers, free amino groups, and selective for specific sugar epimers in competition experiments.

Enantioselective Synthesis of Substituted δ-Lactones by Cooperative Oxidative N-Heterocyclic Carbene and Lewis Acid Catalysis.

Efficient construction of complex cylcopentane- or cyclohexane-fused δ-lactones employing redox activation of enals using a chiral N-heterocyclic carbene and LiCl as cooperative catalysts is described. The organocascade proceeds with excellent diastereo- (>99:1) and enantioselectivity (up to >99% ee) and comprises the formation of three bonds with three contiguous stereocenters.

Asymmetric synthesis of highly substituted β-lactones through oxidative carbene catalysis with LiCl as cooperative Lewis acid.

The reaction of enals with β-diketones, β-ketoesters, and malonates bearing a β-oxyalkyl substituent at the α-position by oxidative NHC catalysis to provide highly substituted β-lactones is described. Reactions occur with excellent diastereo- and enantioselectivity. The organo cascade comprises two CC bond formations and one CO bond formation.