Martin Breugst

Mechanistic studies establish that ketone-mediated α-C–H functionalization of unprotected alicyclic amines proceeds via concerted hydride transfer from monomeric lithium amides, in competition with N -addition to the oxidant.

The synthesis of arylacetamides has been developed from arylacetohydrazides and amines using TBHP and catalytic amounts of I2, affording the products in good-to-excellent yields. The protocol features the use of a green oxidant, room-temperature conditions, a wide scope with excellent functional group tolerance, late-stage modification for drug molecules, and gram-scale synthesis of efaproxiral. The mechanistic studies supported by CV and computational data revealed that the underexplored arylacetyl radical, generated in situ via oxidative denitrogenation of arylacetohydrazide, is involved in the N-acylation reaction with amines.

The stereochemical outcomes of pericyclic reactions provide direct insight into the geometry and directionality of concerted bond reorganization. Although torquoselectivity has emerged as a defining concept for electrocyclizations, an analogous principle for sigmatropic rearrangements on a single cyclic π system has remained unknown. We report that a homoannulene‐based photoswitch undergoes an auxiliary‐controlled, stereoselective photochemical [1,11]‐sigmatropic rearrangement, thereby establishing selectivity over directional migration on a single cyclic π framework. We coin the term calderoselectivity for such an unreported stereoselective sigmatropic rearrangement. The switching process is reversible, proceeds to photostationary mixtures of homoannulene and iso ‐homoannulene isomers, and furnishes diastereomeric products in a 56:44 ratio; combined chiral HPLC, NMR, ECD, and DFT studies assign the major directionality of acyl migration in pro‐ R directionality. This study provides the first experimental realization of calderoselectivity and reveals a direct analogue in sigmatropic rearrangements to torquoselectivity with implications for both mechanistic physical organic chemistry and chiroptical switch design.

The stereochemical outcomes of pericyclic reactions provide direct insight into the geometry and directionality of concerted bond reorganization. Although torquoselectivity has emerged as a defining concept for electrocyclizations, an analogous principle for sigmatropic rearrangements on a single cyclic π system has remained unknown. We report that a homoannulene‐based photoswitch undergoes an auxiliary‐controlled, stereoselective photochemical [1,11]‐sigmatropic rearrangement, thereby establishing selectivity over directional migration on a single cyclic π framework. We coin the term calderoselectivity for such an unreported stereoselective sigmatropic rearrangement. The switching process is reversible, proceeds to photostationary mixtures of homoannulene and iso ‐homoannulene isomers, and furnishes diastereomeric products in a 56:44 ratio; combined chiral HPLC, NMR, ECD, and DFT studies assign the major directionality of acyl migration in pro‐ R directionality. This study provides the first experimental realization of calderoselectivity and reveals a direct analogue in sigmatropic rearrangements to torquoselectivity with implications for both mechanistic physical organic chemistry and chiroptical switch design.

While in high demand, synthetic methods for intermolecular dehydrogenative hetero N–N coupling reactions remain very rare, in spite of some seminal but limited developments these past few years. This is largely due to the broad diversity of more favorable side reactions that can occur upon the oxidation of organic amines, amides and related, such as competing C–C or C–N couplings, or even skeletal rearrangements. We report herein our latest research efforts in this field, focused on aromatic and aliphatic N-alkoxy carbamates and their dehydrogenative N–N coupling with benzotriazoles. This process is enabled by very simple and mild reaction conditions, affording the coupling products in high yields, even at a larger scale. The ability of the PIDA (diacetoxyiodobenzene) oxidant to produce the N–N bond is demonstrated by an unprecedented X-ray structure of the N–N–N–N–O scaffold. Mechanistic insights, including radical trapping and isotope competition experiments, as well as computational investigations, suggest a radical mechanism.

Carbonyl–olefin and carbonyl–alkyne metathesis reactions are powerful strategies for the formation of carbon–carbon bonds, offering access to structurally diverse molecules. Unlike traditional olefin metathesis, these reactions involve a formal exchange reaction between a carbonyl compound and an alkene or alkyne, enabling efficient access to cyclic and acyclic frameworks under milder and more selective conditions. Recent advances in catalyst design, including Lewis acids, Brønsted acids, and organocatalysts have significantly expanded the scope, efficiency, and functional group tolerance of these reactions. This review covers recent developments across both reaction classes, with emphasis on mechanistic understanding, catalyst design, and representative applications in synthesis. Remaining challenges are also discussed alongside emerging opportunities that position carbonyl metathesis as an increasingly indispensable tool in modern synthetic chemistry.

The past decades have seen significant expansion of the nucleic acid space with the development of modified artificial base pairs based on natural nucleic acid analogues and even entirely new designed base pairs. This expansion has led to tremendous potential for applications such as site-specific labeling and structural investigations. However, natural nucleic acids rely strongly on hydrogen bonding as the attraction force, which has driven the development of artificial base pairs that adapt this mechanism. To achieve orthogonality with natural bases, unnatural base pairs with alternative attraction forces, such as hydrophobic interactions, have been developed which however can perturb duplex structures. Our work introduces a completely newly designed artificial base pair that leverages halogen bonding (R-Hal···) as a directional hydrogen bonding-like interaction. We report computational studies that led to the development of this novel unnatural base pair and its synthesis. Our results demonstrate the successful acceptance of a bulky iodinated nucleoside triphosphate by KlenTaq DNA polymerase, enabling the selective enzymatic synthesis of a DNA strand containing the dIIPO-doIPP base pair. Our work presents the first demonstration of a novel base pair with halogen bonding potential that is enzymatically incorporated into DNA.

Thioureas and related noncovalent catalysts constitute a key pillar of stereoselective catalysis, yet their practical utility is often limited by high catalyst loadings or modest reactivity. Here we introduce a simple and broadly applicable strategy to enhance both the activity and selectivity of these catalysts through the addition of small amounts of molecular iodine (typically 10 mol% relative to the organocatalyst). The concept is effective across multiple classes of organic reactions and applies to hydrogen-bond, halogen-bond, and chalcogen-bond donors alike. Mechanistic and computational studies support the formation of an iodine-thiourea complex as the catalytically active species, providing a coherent rationale for the observed rate and selectivity enhancements.

The interaction enthalpies of differently substituted cationic pnictogen-, chalcogen-, and halogen-bond donors with the fluoride anion have been analyzed computationally and correlated against different predictors to identify more active catalysts.

C–N axially chiral carbazoles were synthesized from C–C axially chiral biaryls via an axial-to-axial chirality transfer in a Buchwald–Hartwig amination. The reaction proceeds via two diastereomeric intermediates under Curtin–Hammett conditions.