Volume 2 Issue 3, March 2023

Timothy Noël, a professor at the University of Amsterdam and Chair of Flow Chemistry, talks to Nature Synthesis about how flow technologies and photocatalytic methods enable C(sp³)–H functionalization reactions.

Alison Wendlandt, an Assistant Professor of Chemistry at the Massachusetts Institute of Technology, talks to Nature Synthesis about how hydrogen atom transfer can be used to selectively edit C(sp³)–H bonds in sugars and polyols.

Anticancer drugs are typically obtained through complex chemical synthesis or from plant extraction. Now, an engineered yeast strain enables a de novo biosynthetic approach to the anticancer building block catharanthine, using methanol as a carbon feedstock.

Preparing molecules with multiple ¹³C labels is difficult owing to the lack of available ¹³C-labelled reagents. Now, a hydroformylation approach to the synthesis of [¹³C₃]propionaldehyde, using gas surrogates, provides a straightforward method to prepare bioactive molecules with three ¹³C labels.

A modular and general method to make unprotected aryl C-glycosides with high stereoselectivity from simple starting materials has been developed based on photoredox, Ni-catalysed cross-coupling. Key to success is the use of an allyl glycosyl sulfone in combination with tolyl sulfinate as the synthetic equivalent of a glycosyl anion.

Cross-coupling between two different C–H bonds with the release of hydrogen is a powerful yet challenging transformation. Catalytic methods that harness photo- or electrochemistry facilitate thermodynamically unfavourable coupling reactions under mild conditions. This Perspective outlines strategies based on photoinduced hydrogen-atom transfer for the cross-coupling of various hydrocarbons.

Anodic C(sp³)–H bond oxidative functionalization that involve C(sp³)–M, a C(sp³) radical or a C(sp³) cation intermediate with hydrogen evolution can be achieved by direct and indirect electrolysis. This Review discusses both strategies, and gives examples of the electrochemical methods developed for such functionalization reactions.

The synthesis of catharanthine, the direct precursor of anticancer drugs vinblastine and vincristine, is challenging due to its structural complexity. Here synthetic biology enables the construction of a Pichia pastoris cell factory for the biosynthesis and potentially scalable production of catharanthine from simple carbon sources.

The incorporation of multiple carbon labels into drug candidates is a difficult synthetic challenge. Here an operationally simple method for the preparation of multi-carbon-labelled isotopologues of active pharmaceutical ingredients and other bioactive molecules, through a combined catalytic three-gas surrogate hydroformylation strategy, is reported.

The synthesis of aryl C-glycosides often requires manipulation of protecting groups. Here a general method to prepare aryl C-glycosides from unprotected and stable starting materials has been achieved by photoredox, Ni-catalysed cross-coupling. The protocol was also applied in the synthesis of several sugar–drug conjugates and gliflozin drug molecules.

The use of acyl functional groups as nucleophilic synthons in transition metal-catalysed carbometallation of unsaturated hydrocarbons remains challenging. Here, nickel-catalysed acylzincation reactions of alkynes and alkenes with organozinc reagents under 1 atm of CO are developed, featuring high functional group tolerance, a broad substrate scope and mild conditions.

The synthesis of benzylic carbocations bearing meta-hydroxyl substituents is difficult due to their lack of resonance stabilization. Now, a catalytic enantioselective reaction between meta-hydroxyl triarylmethanols and indoles, proceeding through a meta-hydroxyl triarylmethyl cation, is reported. A range of chiral tetraarylmethanes with anticancer activity are prepared.

The synthesis of interlocking molecular [n]catenanes of organic polyhedra (n = 2–3) and rings (n = 2–130) is established; however, the analogous chemistry of infinite 3D structures remains undeveloped. Now, reticular chemistry enables the synthesis of crystalline [∞]catenane covalent organic frameworks constructed from interlocking organic polyhedra.

Synthesizing Se-based nanocrystals with large diameters remains challenging. Here, a reactivity-controlled epitaxial growth strategy was demonstrated to synthesize nanocrystals of ZnSe, CdSe and PbSe with average diameters of 35 nm, 76 nm and 87 nm, respectively. The large ZnSe nanocrystals emitted pure blue light, which is important for display technology.