R. Jiang

Nature Chemistry, Published online: 01 May 2023; doi:10.1038/s41557-023-01165-6

Catalytic enantioselective approaches to access chiral organophosphorus compounds are rare. A two-stage catalytic strategy for the synthesis of diverse enantioenriched P(V) compounds has now been developed: a bifunctional iminophosphorane superbase enables enantioselective nucleophilic desymmetrization, followed by downstream enantiospecific diversification of the resulting intermediate by substitution with medicinally relevant O-, N- and S-based nucleophiles.

Pairing a cationic chromophore with a chiral anion renders photocatalyzed [2+2] styrene cycloadditions enantioselective.

An N-heterocyclic carbene acts as a single carbon atom donor in converting α,β-unsaturated amides into homologated lactams.

Nature Catalysis, Published online: 19 January 2023; doi:10.1038/s41929-022-00908-x

The design of complementary catalysts to target different C–H bonds in a specific molecule is challenging. Now, a pair of P450-based carbene transferase enzymes is engineered, which can selectively cyanomethylate either a C(sp3)–H or arene C(sp2)–H bond present in the same substrate.

Magnesium hydride, generated in situ by solvothermal treatment of sodium hydride and magnesium iodide in tetrahydrofuran, was found capable of inducing regio and stereocontrolled hydromagnesiation of 2-aryl-1,3-dienes to form allylmagnesium species. Downstream functionalization of the resulting allylmagnesium species with various electrophiles provided synthetically valuable synthons such as homoallylic alcohols and allylsilanes.

Abstract

A protocol for the generation of allylmagnesium reagents from 2-aryl-1,3-dienes was developed using magnesium hydride (MgH₂) that is generated in situ by solvothermal treatment of sodium hydride (NaH) and magnesium iodide (MgI₂) in tetrahydrofuran (THF). Downstream functionalization of the resulting allylmagnesium reagents with carbonyl compounds or alkyl (pseudo)halides delivers branched products having an allylic quaternary carbon center, whereas that with chlorosilanes resulted in formation of linear allylsilanes in regio and stereoselective manners. Further derivatizations of the homoallylic alcohols and allylsilanes were also demonstrated.

The [2+2]-heterocycloaddition between alkenes and carbonyls is a formidable strategy for the synthesis of complex strained 3D architectures. This Review provides an overview on the recent development of [2+2]-heterocycloadditions driven by visible light. The diverse synthetic approaches are presented with special emphasis on the involved reaction mechanisms along with possible future directions of the field.

Abstract

The synthesis of four membered heterocycles usually requires multi-step procedures and prefunctionalized reactants. A straightforward alternative is the photochemical [2+2]-heterocycloaddition between an alkene and a carbonyl derivative, conventionally based on the photoexcitation of this latter. However, this approach is limited by the absorption profile of the carbonyl, requiring in most of the cases the use of high-energy UV-light, that often results in undesired side reactions and/or the degradation of the reaction components. The development of new and milder visible light-driven [2+2]-heterocycloadditions is, therefore, highly desirable. In this Review, we highlight the most relevant achievements in the development of [2+2]-heterocycloadditions promoted by visible light, with a particular emphasis on the involved reaction mechanisms. The open challenges will also be discussed, suggesting new possible evolutions, and stimulating new methodological developments in the field.

Nature Chemistry, Published online: 12 January 2023; doi:10.1038/s41557-022-01119-4

Controlling various selectivities in radical reactions presents both formidable challenges and great opportunities. Now, Co(II)-based metalloradical catalysis has enabled the concurrent control of multiple convergences and selectivities in intermolecular radical allylic C−H amination. The reaction provides access to valuable chiral α-tertiary amines directly from an isomeric mixture of alkenes.

Nature Catalysis, Published online: 12 January 2023; doi:10.1038/s41929-022-00899-9

Insights on the mechanistic differences between artificial metalloenzymes (ArMs) with non-native metal centres and the free cofactor or natural enzymes are scarce. Now, a detailed mechanistic analysis of a cyclopropanation reaction catalysed by such an ArM is provided, revealing intriguing differences to the natural system.

Palladium-catalyzed C−H arylation of tryptophan-containing peptides with readily accessible and modular arylthianthrenium salts was investigated. The modular nature of this arylating agent allowed the expedient stitching of tryptophan-containing peptides with drug, natural product, and peptidic scaffolds by forging sterically congested biaryl linkages.

Abstract

Bioorthogonal late-stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging, among other applications. Herein, we report on a palladium-catalyzed C−H arylation of tryptophan-containing peptides with readily accessible and modular arylthianthrenium salts. Under exceedingly mild reaction conditions, the late-stage diversification of structurally complex peptides was accomplished. The tunability and ease of preparation of arylthianthrenium salts allowed the expedient stitching of tryptophan-containing peptides with drug, natural product, and peptidic scaffolds by forging sterically congested biaryl linkages. The robustness of the palladium catalysis regime was reflected by the full tolerance of a plethora of sensitive and coordinating functional groups. Hence, our manifold enabled efficient access to highly decorated, labelled, conjugated, and ligated linear and cyclic peptides.

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition of dialkylzinc reagents to cyclic enones with iridium-catalyzed asymmetric allylic substitution reaction. Good to excellent yields, diastereoselectivity and enantioselectivity can be obtained. The current reaction can achieve the stereodivergent construction of nonadjacent stereocenters.

Abstract

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition of dialkylzinc reagents to cyclic enones with iridium-catalyzed asymmetric allylic substitution reaction. Good to excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction of adjacent stereocenters (1,2-position) reported in the literature, the current reaction can achieve the stereodivergent construction of nonadjacent stereocenters (1,3-position) by a proper combination of two chiral catalysts with different enantiomers.

Nature Chemistry, Published online: 30 December 2022; doi:10.1038/s41557-022-01110-z

Asymmetric systems for catalytic carbohydrate functionalization are mostly limited to chiral copper complexes and organocatalysts. Now, a synergistic chiral Rh(I)- and organoboron-catalysed site-selective functionalization of carbohydrate polyols has been developed, giving stereocontrolled access to biologically relevant arylhydronaphthalene glycosides. Enantio-, diastereo-, regio- and anomeric control and dynamic kinetic resolution were found to be concomitantly operative.