Nature Chemistry, Published online: 15 June 2026; doi:10.1038/s41557-026-02178-7The selective functionalization of unprotected amines with alkenes remains a challenge in contemporary synthesis. Now a strategy has been developed for an alkyl swap of N-methylamines, enabling late-stage bioconjugation and peptide modification. The resulting retrosynthetic disconnection also streamlines the preparation of several pharmaceuticals and medicinally relevant compounds.

Methanogenic archaea use the one-component system AmzR to sense methylamines and regulate the expression of methylamine-metabolizing genes. Unlike other prokaryotic one-component systems, the DNA-binding motif of AmzR resembles a structural fold typically found in eukaryotic transcription factors. This discovery narrows the gap between prokaryotic and eukaryotic regulatory proteins.

Overalkylation is a common side reaction that typically prevents the synthesis of tertiary N-methylamines from secondary amines, using alkyl iodides and other reactive electrophiles. Herein, we presen...

Alkylamines are ubiquitous in pharmaceutically and medicinally relevant compounds (Fig. 1a), where they often serve as key pharmacophores or modulate critical properties such as solubility, basicity and target engagement. Their central role in drug design has driven the development of medicinal chemistry strategies focused on fine-tuning alkylamine motifs to optimize biological activity and absorption, distribution, metabolism and excretion (ADME) profiles1,2. Secondary alkylamines, being more membrane permeable and metabolically stable than primary amines, have found widespread use in a variety of biological settings3. This prevalence of biologically active compounds (including several high-grossing pharmaceuticals) containing secondary alkylamines invites late-stage functionalization as a means for rapid structural diversification. Consequently, peripheral functionalization of complex amines has emerged as a cornerstone of modern medicinal chemistry. Despite this progress, the direct, site-selective replacement of alkyl groups at a late stage remains largely underexplored, highlighting a substantial unmet need in the molecular editing toolkit4. The elegant use of transition-metal catalysis, often in combination with directing group strategies, has enabled selective C(sp3)–H functionalization of amines at the β-, γ- and δ-positions5,6,7,8,9,10,11,12,13,14, as well as at more remote sites15,16. However, methods for achieving selective functionalization at the α-position remain limited to specific substrate classes and are restricted to tertiary,...

Methanogenic archaea use the one-component system AmzR to sense methylamines and regulate the expression of methylamine-metabolizing genes. Unlike other prokaryotic one-component systems, the DNA-bind...

Methanogenic archaea use the one-component system AmzR to sense methylamines and regulate the expression of methylamine-metabolizing genes. Unlike other prokaryotic one-component systems, the DNA-bind...

For more than a century, chemists have been building complex molecules step by step—bond by bond, atom by atom. But what if, instead of painstakingly reassembling molecules, they could be directly "rewritten"?

Overalkylation is a common side reaction that typically prevents the synthesis of tertiary N-methylamines from secondary amines, using alkyl iodides and other reactive electrophiles. Herein, we…

We report a general copper-catalyzed hydrogenative reduction of thioureas to N-methylamine and N,N-dimethylamine (10 examples, 42-99% carbon utilization rate) using PhSiH3 as the hydrogenation reagent...