• Two molecules linked by a lightning bolt-like bond formation event

    Hydrogen atom transfer (HAT) is a key process for the functionalization of C(sp3)-H bonds, enabling the synthesis of complex molecules from hydrocarbon chemical feedstocks. This Focus highlights innovations in technology, catalysis and methodology which seek to overcome challenges in the area.

  • Twitter avatar

    Follow us @NatureSynthesis to hear about the latest content published in the journal.

Nature Synthesis is a Transformative Journal; authors can publish using the traditional publishing route OR via immediate gold Open Access.

Our Open Access option complies with funder and institutional requirements.


  • Direct, stereocontrolled functionalization of ubiquitous C(sp3)–H bonds represents the most efficient route towards highly valuable molecules from feedstock chemicals. Now, diverse, enantioenriched, unnatural α-amino acids are obtained from readily available carboxylic acids in one step via iron-catalysed asymmetric nitrene transfer, overcoming the reactivity and selectivity challenges of intermolecular C–H amination.

    • Tuan Anh Trinh
    • Jennifer M. Schomaker
    News & Views
  • The amination of CH bonds is a sustainable approach to prepare important nitrogen-containing molecules; however, regio- and stereoselectivity is difficult to control. Now the synthesis of α-monosubstituted and α,α-disubstituted α-amino acids from abundant carboxylic acids has been achieved through Fe-catalysed asymmetric intermolecular C(sp3)–H amination by directed stereocontrolled nitrene insertion.

    • Chen-Xi Ye
    • Drew R. Dansby
    • Eric Meggers
    Article Open Access
  • Complex molecule synthesis involves speculative retrosynthetic planning and resource-intensive experimental evaluation. Now, a complementary strategy is reported that combines human-generated synthetic plans with computational prediction to accelerate this process. A machine learning model was trained to predict the yield of radical cyclization and guide the syntheses of clovane sesquiterpenoids.

    • Pengpeng Zhang
    • Jungmin Eun
    • Timothy R. Newhouse
  • Preparing enantioenriched aliphatic amines from readily available feedstocks is challenging to achieve. Now, direct enantioconvergent amination of racemic secondary alcohols using a variety of aliphatic primary amines is reported, catalysed by chiral iridium and phosphoric acid species. This atom-economical strategy streamlines the enantioselective synthesis of N-containing commercial drugs and analogues.

    • Xiao Qian Ng
    • Ching Si Lim
    • Yu Zhao
  • BODIPYs possessing boron-stereogenic centres are rare and it is challenging to develop catalytic methodologies to enantioselectively prepare these molecules. Now, a palladium-catalysed desymmetric intramolecular C–H arylation reaction for the enantioselective synthesis of boron-stereogenic BODIPYs is reported, which gives access to various six- to nine-membered chiral boron heterocycles with good enantioselectivity.

    • Bing Zu
    • Yonghong Guo
    • Chuan He
  • The direct electrosynthesis of acetic acid from CO2 typically has the drawback of CO2 crossover. Now, a cascade approach for the electroreduction of CO2 to CO, followed by CO to acetic acid, is reported in which off-target intermediates are destabilized, leading to an acetic acid Faradaic efficiency of 70%.

    • Roham Dorakhan
    • Ivan Grigioni
    • Edward H. Sargent
  • Combinatorial synthesis has historically been the cornerstone of high-throughput experimentation. In this Review, we discuss the evolution of combinatorial synthesis and envision a future for accelerated materials science through its integration with artificial intelligence. We also evaluate the key aspects of combinatorial synthesis with respect to workflow design.

    • John M. Gregoire
    • Lan Zhou
    • Joel A. Haber
    Review Article
  • Well-defined single-atom alloy (SAA) nanocrystals possess isolated atom centres and tunable electronic properties but are challenging to synthesize. Here, a direct solution-phase synthesis of Cu/CuAu core/shell nanocubes with tunable SAA layers is reported. The Cu/CuAu nanomaterial is highly active for the electrocatalytic conversion of nitrate into ammonia.

    • Qiang Gao
    • Bingqing Yao
    • Huiyuan Zhu
  • Functional-group transfer strategies using surrogates to avoid handling hazardous reagents are often limited to monofunctionalization reactions. Now, an operationally simple and mechanistically distinct photocatalytic transfer strategy for vicinal dihalogenation of carbon–carbon multiple bonds, such as in alkenes, alkynes and allenes, using readily synthesized oxime-based dihalogen surrogates is reported.

    • Muliang Zhang
    • Jinghui Zhang
    • Martin Oestreich