Sheng-Cai Zheng

Metal-Free Direct Intramolecular Carbotrifluoromethylation of Alkenes to Functionalized Trifluoromethyl Azaheterocycles

The first example of a metal-free direct carbotrifluoromethylation of alkenes using inexpensive TMSCF3 as the CF3 source is described. The methodology not only exhibits high chemoselectivity for this transformation but also expands the substrate scope that is difficult to access by known transition-metal-catalyzed methods.

Enantioselective CH Bond Functionalization Triggered by Radical Trifluoromethylation of Unactivated Alkene

An asymmetric unactivated alkene/C-H bond difunctionalization reaction for the concomitant construction of C-CF3 and C-O bonds was realized by using a Cu/Brønsted acid cooperative catalytic system, thus providing facile access to valuable chiral CF3-containing N,O-aminals with excellent regio-, chemo-, and enantioselectivity. Mechanistic studies revealed that this reaction may proceed by an unprecedented 1,5-hydride shift involving activation of unactivated alkenes and a radical trifluoromethylation to initiate subsequent enantioselective functionalization of C-H bonds. Control experiments also suggested that chiral Brønsted acid plays multiple roles and not only controls the stereoselectivity but also increases the reaction rate through activation of Tognis reagent.

Phosphine-Catalyzed Remote β-CH Functionalization of Amines Triggered by Trifluoromethylation of Alkenes: One-Pot Synthesis of Bistrifluoromethylated Enamides and Oxazoles†

An unprecedented phosphine-catalyzed remote β-CH functionalization of amine derivatives triggered by trifluoromethylation of an alkene with Tognis reagent was disclosed. This reaction proceeded through the highly selective and concomitant activation of an unactivated alkene and the β-C sp 3H bond of an amine derivative, providing bistrifluoromethylated enamides in excellent yields with good regio-, chemo-, and stereoselectivity. Furthermore, the newly developed one-pot protocol provides a facile and step-economical access to valuable trisubstituted 5-(trifluoromethyl)oxazoles. Mechanistic studies showed that this reaction may initiate with a novel phosphine-catalyzed radical trifluoromethylation of unactivated alkene via a phosphorus radical cation.

Highly Enantioselective Kinetic Resolution of Axially Chiral BINAM Derivatives Catalyzed by a Brønsted Acid

A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid-catalyzed imine formation and transfer hydrogenation cascade process was developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.

Metal-free direct 1,6- and 1,2-difunctionalization triggered by radical trifluoromethylation of alkenes.

A metal-free direct remote C-H functionalization triggered by radical trifluoromethylation of alkenes was explored, realizing highly selective 1,6-difunctionalization of alkenes toward valuable trifluoromethyl α-hydroxycarbonyl compounds. Furthermore, a metal-free direct intermolecular regioselective 1,2-oxytrifluoromethylation of alkenes is also disclosed. With Tognis reagent as both the CF3 source and oxidant, the reaction exhibits a broad substrate scope with excellent functionality tolerance under mild metal-free conditions, thus showing great potential for synthetic utility.

Asymmetric Synthesis of Axially Chiral Isoquinolones: Nickel‐Catalyzed Denitrogenative Transannulation

The first Ni(0)/bis(oxazoline)-catalyzed asymmetric denitrogenative transannulation of 1,2,3-benzotriazin-4(3H)-ones with bulky internal alkynes to form novel axially chiral isoquinolones in an atroposelective manner has been developed. This method provides direct asymmetric access to axially chiral isoquinolones with excellent functional-group tolerance in excellent yields and stereoselectivities from readily available starting materials under mild reaction conditions. These axially chiral isoquinolones exhibit high cytotoxicity against a number of human cancer cell lines. DFT calculations reveal the nature of the transition state in the key annulation step.

Trifluoromethylation‐Initiated Remote Cross‐Coupling of Carbonyl Compounds to Form Carbon–Heteroatom/Carbon Bonds

By involving the reversal of conventional reactivity expectations without external oxidants, we describe a novel and convenient protocol of remote cross-coupling of carbonyl compounds with a series of common and simple nucleophiles. This cross-coupling is triggered by radical trifluoromethylation of alkenes, thereby achieving highly selective remote difunctionalization of alkenes and α-position of the carbonyl group for facile access to trifluoromethyl α-halo- and α-cyanocarbonyl compounds. The reaction exhibits a broad substrate scope with excellent functionality tolerance and many different types of nucleophiles; further synthetic applicability of the obtained compounds proved to be suitable, thus showing great potential for synthetic utility.

Construction of Tropane Derivatives by the Organocatalytic Asymmetric Dearomatization of Isoquinolines

A chiral-NHC-catalyzed highly diastereo- and enantioselective dearomatizing double Mannich reaction of isoquinolines was developed that provides a powerful and straightforward synthetic route toward substituted tropane derivatives with four contiguous stereocenters. A unique feature of this strategy is the use of readily available isoquinolines to provide two reactive sites for dearomatization, thus opening up an unprecedented approach to tropane derivatives with excellent stereoselectivity. The four-component reactions proceeded smoothly with good results. Thus, the present method is suitable for the diversity-oriented synthesis of useful tropane derivatives with high efficiency.

Organocatalytic atroposelective synthesis of axially chiral styrenes

Axially chiral compounds are widespread in biologically active compounds and are useful chiral ligands or organocatalysts in asymmetric catalysis. It is well-known that styrenes are one of the most abundant and principal feedstocks and thus represent excellent prospective building blocks for chemical synthesis. Driven by the development of atroposelective synthesis of axially chiral styrene derivatives, we discovered herein the asymmetric organocatalytic approach via direct Michael addition reaction of substituted diones/ketone esters/malononitrile to alkynals. The axially chiral styrene compounds were produced with good chemical yields, enantioselectivities and almost complete E/Z-selectivities through a secondary amine-catalysed iminium activation strategy under mild conditions. Such structural motifs are important precursors for further transformations into biologically active compounds and synthetic useful intermediates and may have potential applications in asymmetric synthesis as olefin ligands or organocatalysts.

Erratum: Organocatalytic atroposelective synthesis of axially chiral styrenes

This corrects the article DOI: 10.1038/ncomms15238.