Hongli Bao

Catalytic enantioselective allylic amination of unactivated terminal olefins via an Ene reaction/[2,3]-rearrangement

The enantioselective allylic amination of unactivated terminal olefins represents a direct and attractive strategy for the synthesis of enantioenriched amines. We have developed the first use of a nitrogen-containing reagent and a chiral palladium catalyst to convert unfunctionalized olefins into enantioenriched allylic amines via an ene reaction/[2,3]-rearrangement.

Catalytic enantioselective [2,3]-rearrangements of amine N-oxides.

The first Pd-catalyzed enantioselective [2,3]-rearrangement of allylic amine N-oxides is described, which formally represents an asymmetric Meisenheimer rearrangement. The mild reaction conditions enable the synthesis of chiral nonracemic aliphatic allylic alcohol derivatives with reactive functional groups. On the basis of preliminary studies, a cyclization-mediated mechanism is proposed.

Iron-Catalyzed Decarboxylative Alkyl Etherification of Vinylarenes with Aliphatic Acids as the Alkyl Source

Because of the lack of effective alkylating reagents, alkyl etherification of olefins with general alkyl groups has not been previously reported. In this work, a variety of alkyl diacyl peroxides and peresters generated from aliphatic acids have been found to enable the first iron-catalyzed alkyl etherification of olefins with general alkyl groups. Primary, secondary and tertiary aliphatic acids are suitable for this reaction, delivering products with yields up to 97 %. Primary and secondary alcohols react well, affording products in up to 91 % yield.

Iron-Catalyzed C–H Alkylation of Heterocyclic C–H Bonds

An efficient, iron-catalyzed C-H alkylation of benzothiazoles by using alkyl diacyl peroxides and alkyl tert-butyl peresters which are readily accessible from carboxylic acids to synthesize 2-alkylbenzothiazoles is developed. This reaction is environmentally benign and compatible with a broad range of functional groups. Various primary, secondary, and tertiary alkyl groups can be efficiently incorporated into diverse benzothiazoles. The effectiveness of this method is illustrated by late-stage functionalization of biologically active heterocycles.

Copper-Catalyzed Regioselective 1,2-Alkylesterification of Dienes to Allylic Esters.

Copper catalyzed 1,2-alkylesterification of 1,3-dienes with diacyl peroxides affords branched allylic esters in excellent regioselectivity, including products with a newly generated fully substituted carbon center. The only byproduct is CO2. The reaction proceeds by a radical mechanism as suggested by spin trap and crossover experiments.

Allylic Functionalization of Unactivated Olefins with Grignard Reagents

New advances in the functionalization of unactivated olefins with carbon nucleophiles have provided more efficient and practical approaches to convert inexpensive starting materials into valuable products. Recent examples have been reported with stabilized carbon nucleophiles, tethered carbon nucleophiles, diazoesters, and trifluoromethane donors. A general method for functionalizing olefins with aromatic, aliphatic, and vinyl Grignard reagents was developed. In a one-pot process, olefins are oxidized by a commercially available reagent to allylic electrophiles, which undergo selective copper-catalyzed allylic alkylation with Grignard reagents. Products are formed in high yield and with high regioselectivity. This was utilized to synthesize a series of skipped dienes, a class of compounds that are prevalent in natural products and are difficult to synthesize by known allylic alkylation methods.

Microwave-assisted and Efficient One-Pot Synthesis of Substituted 1,2,4-Triazoles

An efficient microwave-assisted one-pot and three-component synthesis of substituted 1,2,4-triazoles has been achieved utilizing substituted primary amines.

Iron-Catalyzed Carboamination of Olefins: Synthesis of Amines and Disubstituted β-Amino Acids

Intermolecular carboamination of olefins with general alkyl groups is an unsolved problem. Diastereoselective carboamination of acyclic olefins represents an additional challenge in intermolecular carboaminations. We have developed a general alkylamination of vinylarenes and the unprecedented diastereoselective anti-carboamination of unsaturated esters, generating amines and unnatural β-amino acids. This alkylamination is enabled by difunctional alkylating reagents and the iron catalyst. Alkyl diacyl peroxides, readily synthesized from aliphatic acids, serve as both alkylating reagents and internal oxidizing agents. A computational study suggests that addition of a nitrile to the carbocation is the diastereoselectivity-determining step, and hyperconjugation is proposed to account for the highly diastereoselective anti-carboamination.

Regioselective and diastereoselective aminoarylation of 1,3-dienes

The 1,4-functionalization of dienes is a synthetically useful strategy for incorporating molecular complexity into a class of simple substrates. We report the aminoarylation of acyclic and cyclic 1,3-dienes via the sequential [4+2] cycloaddition with a sulfurdiimide reagent and copper-catalyzed allylic substitution with Grignard reagents. The regioselective and diastereoselective aminoarylation of unsymmetrical dienes is also presented, which highlights the utility of this method for generating products with multiple functional groups and stereocenters.

γ-Amino Butyric Acid (GABA) Synthesis Enabled by Copper-Catalyzed Carboamination of Alkenes

γ-Amino butyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system. Many GABA derivatives are used clinically to prevent or treat neurodegenerative diseases. Copper-catalyzed carboamination of alkenes offers an efficient method to fashion the core structure of GABA derivatives from alkenes. In this reaction, acetonitrile serves as the source of the carbon and nitrogen functionalities used to difunctionalize alkenes. Experimental and density functional theory (DFT) studies were carried out to investigate the mechanism of the reaction, and a copper-catalyzed radical-polar crossover mechanism is proposed.