LongLarf

Synthesis
DOI: 10.1055/a-1804-8859

Compared to universal radical difunctionalizations of alkenes that are performed with organic solvents, such reactions with water as the sole solvent are rarely reported. Concerning the global consensus on environmental issues, we have developed herein a method for the radical oxyazidation of alkenes in pure water. This reaction allows the construction of C–N and C–O bonds in a one-pot process. Styrenes, 1,3-dienes, and unactivated alkenes react smoothly under mild and environmentally benign conditions to afford a wide scope of functionalized azides in excellent yields and selectivities.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Abstract

The chemistry of boron compounds has been profoundly investigated in the last decades, leading to ubiquity in many synthetic applications as well as biologically active molecules. Since the advent of photoredox catalysis, an upsurge in the discovery of suitable radical precursors has been witnessed, and boron is becoming a protagonist in this field. Despite many studies focused on trifluoroborates, the use of boronic acids and esters have received much less attention in this regard. Because of their high oxidation potential, the development of methods to enable their involvement in photocatalyzed reactions is only recent. Nonetheless, this review summarizes novel strategies developed to unlock their role as radical precursors in photochemical reactions and discloses the potential that boronic acids and esters own, when their intrinsic chemical properties are exploited.

Synlett
DOI: 10.1055/s-0040-1719906

Palladium-catalyzed cross-coupling reactions of polyhalogenated heterocycles provide a convenient access to multifold arylated and alkynylated ring systems with a broad spectrum of physical and medicinal properties. Products include thiophenes, selenophenes, pyrroles, indoles, furans, benzofurans, pyrazoles, pyridines, quinolines, pyrimidines, pyrazines, naphthyridines, quinoxalines, and others. The regioselectivity of the coupling reactions is controlled by a combination of electronic and steric parameters. While a number of couplings can be carried out essentially under standard conditions, others require the use of more sophisticated ligands and a thorough optimization of the conditions, such as solvent, temperature, or reaction time. The present Account provides a personalized overview of coupling reactions of polyhalogenated heterocycles.1 Introduction2 Thiophenes3 Selenophenes4 Pyrroles and Indoles5 Furans and Benzofurans6 Pyrazoles7 Pyridines8 Quinolines9 Pyrimidines and Pyrazines10 Naphthyridines and Quinoxalines11 Miscellaneous12 Conclusions
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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First Aid: Kits of oxyfunctionalisation enzymes may operate as synthetic ‘First Aid’ for chemists, for example in complex natural product total synthesis by providing proficient, ready- and easy-to-use commercial enzymes. In this article we illustrate why enzyme kits could boost the integration of biocatalysis into (synthetic) organic chemistry and how we envision their future application.

Abstract

First Aid Kits are collections of the most important medical equipment required for quick medical assistance. Similarly, enzyme kits can provide a proficient, ready- and easy-to-use collection of biocatalysts that can be applied with high reproducibility. In this article, we illustrate how kits of oxyfunctionalisation enzymes could operate as synthetic ‘First Aid’ for chemists working on complex natural product total synthesis in an early- or late-stage fashion, as well as in lead diversification in drug discovery processes. We reason that enzyme kits could catalyse the integration of biocatalysis into (synthetic) organic chemistry and describe how we envision their future application.

Revealing a radical route: The radical reactivity of the biradical [⋅P(μ-NTer)₂Ṗ] has been investigated. It was possible to synthesize the persistent phosphorus-centered monoradical [⋅P(μ-NTer)₂P−Et] and identify it as a radical intermediate during the addition of bromoethane to [⋅P(μ-NTer)₂Ṗ]. A possible stepwise mechanism of this reaction was formulated and is supported by both detailed quantum chemical calculations and experimental results.

Abstract

The activation of C−Br bonds in various bromoalkanes by the biradical [⋅P(μ-NTer)₂P⋅] (1) (Ter=2,6-bis-(2,4,6-trimethylphenyl)-phenyl) is reported, yielding trans-addition products of the type [Br−P(μ-NTer)₂P−R] (2), so-called 1,3-substituted cyclo-1,3-diphospha-2,4-diazanes. This addition reaction, which represents a new easy approach to asymmetrically substituted cyclo-1,3-diphospha-2,4-diazanes, was investigated mechanistically by different spectroscopic methods (NMR, EPR, IR, Raman); the results suggested a stepwise radical reaction mechanism, as evidenced by the in-situ detection of the phosphorus-centered monoradical [⋅P(μ-NTer)₂P-R].< To provide further evidence for the radical mechanism, [⋅P(μ-NTer)₂P-Et] (3Et⋅) was synthesized directly by reduction of the bromoethane addition product [Br-P(μ-NTer)₂P-Et] (2 a) with magnesium, resulting in the formation of the persistent phosphorus-centered monoradical [⋅P(μ-NTer)₂P-Et], which could be isolated and fully characterized, including single-crystal X-ray diffraction. Comparison of the EPR spectrum of the radical intermediate in the addition reaction with that of the synthesized new [⋅P(μ-NTer)₂P-Et] radical clearly proves the existence of radicals over the course of the reaction of biradical [⋅P(μ-NTer)₂P⋅] (1) with bromoethane. Extensive DFT and coupled cluster calculations corroborate the experimental data for a radical mechanism in the reaction of biradical [⋅P(μ-NTer)₂P⋅] with EtBr. In the field of hetero-cyclobutane-1,3-diyls, the demonstration of a stepwise radical reaction represents a new aspect and closes the gap between P-centered biradicals and P-centered monoradicals in terms of radical reactivity.

A novel catalytic approach for the preparation of polymerizable bicyclic carbonates allows the synthesis of a wide range of unique heterocycles. The stereochemical configuration of the epoxy alcohol substrate plays a crucial role, determining the chemoselectivity profile of this coupling manifold. The synthetic potential of these bicyclic six-membered carbonates was examined, and their successful ring-opening polymerization under mild conditions gives new incentives for relatively rigid polycarbonate architectures.

Abstract

A new catalytic route has been developed for the coupling of epoxides and CO₂ affording polymerizable six-membered bicyclic carbonates. Cyclic epoxides equipped with a β-positioned OH group can be transformed into structurally diverse bicyclic cyclic carbonates in good yields and with high selectivity. Key to the chemo-selectivity is the difference between the reactivity of syn- and anti-configured epoxy alcohols, with the latter leading to six-membered ring carbonate formation in the presence of a binary Al^III aminotriphenolate complex/DIPEA catalyst. X-ray analyses show that the conversion of the syn-configured substrate evolves via a standard double inversion pathway providing a five-membered carbonate product, whereas the anti-isomer allows for activation of the oxirane unit of the substrate opposite to the pendent alcohol. The potential use of these bicyclic products is shown in ring-opening polymerization offering access to rigid polycarbonates with improved thermal resistance.

Nature Communications, Published online: 21 April 2022; doi:10.1038/s41467-022-29900-6

An enantioselective Minisci reaction between pyridines and prochiral α-hydroxy radicals has been developed. Hydrogen atom transfer is used to generate the latter from simple alcohols and the reaction formally constitutes the couple of two C−H bonds to form a new C−C bond in a process that is highly enantioselective and regioselective. Computational studies provide insight into the origins of selectivity.

Abstract

Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α-amino radical coupling partners. We report a substantial evolution of the enantioselective Minisci reaction that enables α-hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through the direct oxidative coupling of two C−H bonds on simple alcohol and pyridine partners through a hydrogen atom transfer (HAT)-driven approach: a challenging process to achieve due to the numerous side reactions that can occur. Our approach is highly regioselective as well as highly enantioselective. Dicumyl peroxide, upon irradiation with 390 nm light, serves as both HAT reagent and oxidant whilst selectivity is controlled by use of a chiral phosphoric acid catalyst. Computational and experimental evidence provide mechanistic insight as to the origin of selectivity, revealing a stereodetermining deprotonation step distinct from the analogous reaction of amide-containing substrates.