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© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., We describe maleic-acid derivatives as robust cysteine-selective reagents for protein labelling with comparable kinetics and superior stability relative to maleimides. Diamide and amido-ester derivatives proved to be efficient protein-labelling species with a common mechanism in which a spontaneous cyclization occurs upon addition to cysteine. Introduction of chlorine atoms in their structures triggers ring hydrolysis or further conjugation with adjacent residues, which results in conjugates that are completely resistant to retro-Michael reactions in the presence of biological thiols and human plasma. By controlling the microenvironment of the reactive site, we can control selectivity towards the hydrolytic pathway, forming homogeneous conjugates. The method is applicable to several scaffolds and enables conjugation of different payloads. The synthetic accessibility of these reagents and the mild conditions required for fast and complete conjugation together with the superior stability of the conjugates make this strategy an important alternative to maleimides in bioconjugation., This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 836698 and under grant agreement N° 852985. Funding from the Scripps Research Institute (A.A.), FCT Portugal (PhD scholarship PD/BD/135512/2018 to C.F.A. and FCT Stimulus CEECIND/00453/2018 to G.J.L.B.) and Agencia Estatal Investigación of Spain (AEI; Grant RTI2018-099592-B-C21 to F.C.) is also acknowledged.

In this paper we outline how dihalohydration reactions of propargylic alcohols can be used to access a wide variety of useful halogenated building blocks. A novel procedure for dibromohydration of alkynes has been developed, and a selection of dichloro and dibromo diols and cyclic ethers were synthesized. The dihalohydration of homo‐propargylic alcohols provides a useful route to 3‐halofurans, which were shown to readily undergo cycloaddition reactions under mild conditions. Finally, a novel ring‐expansion of propargylic alcohols containing a cyclopropylalkyne provides access to halogenated alkenylcyclobutanes.

Aluminum(III) complexes derived from aminotriphenolate ligands are shown to be excellent catalysts for the formation of cyclic sulfites from a range of (functionalized) terminal and internal epoxides, and ex situ generated sulfur dioxide. The developed catalytic protocol is characterized by its operational simplicity, wide scope in epoxide reaction partners, good to excellent isolated yields and mild reaction conditions [50–70 °C, p(SO2)

A highly regioselective catalytic approach has been developed towards carbamates derived from cyclic organic carbonates by reaction of the latter with amine reagents under organocatalytic control. For various combinations of carbonate and amine substrates, an organocatalyst (TBD: 1,5,7-triazabicyclo[4.4.0]dec-5-ene) was used to increase the reaction kinetics while exerting excellent regioselective control. The current method is the first general approach towards the control over the regioselectivity of this reaction using a wide variety of easily accessed substituted organic carbonates.

An efficient and practical aluminium-catalysed approach towards a range of functional oxazolidinones is reported. The method is based on cheap and readily available starting materials including terminal and internal (bicyclic) epoxides and phenyl carbamate. The oxazolidinones serve as highly useful synthons for the high yield preparation of non-symmetrical ureas by nucleophilic ring-opening affording the targeted urea compounds with excellent functional group diversity, high regioselectivity and isolated yields up to >99%.

The efficient and highly selective formation of a wide range of (hetero)cyclic cis-diol scaffolds using powerful aminotriphenolate- based metal catalysts is reported. The key intermediates are cyclic carbonates that are derived in high yield and with high levels of diastereo- and chemo-selectivity from the parent oxirane precursors and carbon dioxide (CO2). Deprotection of the carbonate structures affords synthetically useful cis-diol scaffolds with different ring sizes incorporating various functional groups. This atom-efficient methodology allows for simple construction of diol synthons using cheap and accessible precursors and green metal catalysts, and showcases the use of CO2 as a temporary protecting group.

A broad spectrum of substituted carbonate substrates is subjected to aminolysis in the presence of TBD.

Oxetanes are versatile building blocks in drug-related synthesis to induce property-modulating effects. Whereas related oxiranes are widely used in coupling chemistry with carbon dioxide (CO2) to afford value-added commodity chemicals, oxetane/CO2 couplings remain extremely limited despite the recent advances in the synthesis of these four-membered heterocycles. Here we report an effective one-pot three-component reaction (3CR) strategy for the coupling of (substituted) oxetanes, amines and CO2 to afford a variety of functionalized carbamates with excellent chemoselectivity and good yields. The process is mediated by an aluminium-based catalyst under relatively mild conditions and the developed catalytic methodology can be applied to the formal synthesis of two pharmaceutically relevant carbamates with the 3CR being a key step.

Trans carbamates have been prepared in a diastereoselective approach by a judicious one-pot combination of organic carbonates, prepared in situ, and suitable amine reagents under appropriate reaction conditions. This unprecedented approach allows for stereodivergence from a single oxirane substrate with easy access to both cis and trans carbamate isomers with high stereoselectivity (>19:1 d.r.). Key to the control of the diastereoselective nature of the conversions that lead to the trans carbamates is the in situ formation of trans-configured oligo/polycarbonates through Al catalysis, which provides the targeted products after aminolysis. The present results demonstrate the valorization of a renewable carbon-based reagent (CO2) into new valuable scaffolds and an unusual stereocontrol exerted through carbonate intermediates. A series of control experiments support the proposed mechanistic rationale towards the trans carbamate products, which is based on the trapping of an in situ formed trans-configured oligo/polycarbonate.

Efficient procedures are described for the reaction of cyclic epoxides with carbon dioxide to give cyclic carbonates generally with exclusive or high cis-diastereoselectivity.

Al(III) complexes of amino-tris(phenolate) ligand scaffolds (I) are prepared to attain effective Lewis acidic catalysts.

An aluminum complex based on an amino triphenolate ligand scaffold shows unprecedented high activity (initial TOFs up to 36 000 h–1), broad substrate scope, and functional group tolerance in the formation of highly functional organic carbonates prepared from epoxides and CO2. The developed catalytic protocol is further characterized by low catalyst loadings and relative mild reaction conditions using a cheap, abundant, and nontoxic metal.