LongLarf

The development of a versatile platform for the synthesis of 1,2-difunctionalized bicyclo[1.1.1]pentanes to potentially mimic ortho/meta-substituted arenes is described. The syntheses of useful building blocks bearing alcohol, amine, and carboxylic acid functional handles have been achieved from a simple common intermediate. Several ortho- and meta-substituted benzene analogs, as well as...

A Ni-catalyzed direct decarbonylative borylation of aryl carboxylic acids with B₂cat₂ has been established. B₂cat₂ serves as a borylating agent, but also activates the carboxylic acid substrate towards decarbonylative coupling, playing a dual role in this reaction. A combination of experimental and computational studies reveals that the reaction proceeds through a hitherto unknown concerted decarbonylation and reductive elimination step.

Abstract

The Ni-catalyzed decarbonylative borylation of (hetero)aryl carboxylic acids with B₂cat₂ has been achieved without recourse to any additives. This Ni-catalyzed method exhibits a broad substrate scope covering poorly reactive non-ortho-substituted (hetero)aryl carboxylic acids, and tolerates diverse functional groups including some of the groups active to Ni⁰ catalysts. The key to achieve this decarbonylative borylation reaction is the choice of B₂cat₂ as a coupling partner that not only acts as a borylating reagent, but also chemoselectively activates aryl carboxylic acids towards oxidative addition of their C(acyl)−O bond to Ni⁰ catalyst via the formation of acyloxyboron compounds. A combination of experimental and computational studies reveals a detailed plausible mechanism for this reaction system, which involves a hitherto unknown concerted decarbonylation and reductive elimination step that generates the aryl boronic ester product. This mode of boron-promoted carboxylic acid activation is also applicable to other types of reactions.

Synthesis
DOI: 10.1055/a-1509-5541

This review summarizes the most relevant advancements made in the photocatalyzed synthesis of sulfones, thioethers, and sulfonamides from 2017 to the beginning of 2021. Synthetic strategies towards the construction of sulfur–carbon bonds are discussed together with the proposed reaction mechanisms. Interestingly, sulfur-based functional groups, which are of fundamental importance for the pharmaceutical field, can be assembled by photocatalysis in an easy and straightforward way under milder reaction conditions employing less toxic and expensive sulfur sources in comparison with common strategies.1 Introduction2 Sulfones2.1 Sodium Sulfinates and Sulfinic Acids2.2 Sulfonyl Halides2.3 Sulfonyl Hydrazones2.4 Sulfur Dioxide Surrogates2.5 Miscellaneous3 Thioethers4 Sulfonamides5 Conclusions
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

N-atom deletion from N-heterocycles via N-sulfonylazidonation, Curtius-type rearrangement and rearrangement of 1,2-diazene intermediates is described. It provides a unique opportunity to achieve ring contraction of (n+1)-membered N-heterocycles to n-membered cycles.

Abstract

Excising the nitrogen in secondary amines, and coupling the two residual fragments is a skeletal editing strategy that can be used to construct molecules with new skeletons, but which has been largely unexplored. Here we report a versatile method of N-atom excision from N-heterocycles. The process uses readily available N-heterocycles as substrates, and proceeds by N-sulfonylazidonation followed by the rearrangement of sulfamoyl azide intermediates, providing various cyclic products. Examples are provided of deletion of nitrogen from natural products, synthesis of chiral O-heterocycles from commercially available chiral β-amino alcohols, formal inert C−H functionalization through a sequence of N-directed C−H functionalization and N-atom deletion reactions in which the N-atom can serve as a traceless directing group.

A three-step synthesis leading to the trans-stilbene molecular scaffold was successfully designed and performed. In order to carry out this synthetic pathway, a highly selective and high yielding oxidative Heck cross-coupling method was developed and optimized. A trans-stilbene derivative [(E)-5-(2-([1,1′-biphenyl]-4-yl)vinyl)-2-hydroxybenzoic acid]] required in a medicinal chemistry project was successfully up-scaled (>1000×) and exploited for the production of the substance on a multi-gram (150 g) scale.

Abstract

A selective oxidative Heck cross-coupling method was developed and optimized as a pivotal step for a synthetic route leading to the trans-stilbene framework. The developed method and synthesis were needed in a SAR study in progress that concerned design and development of an inhibitor for the human cell xCT antiporter system. The developed oxidative Heck cross-coupling method was examined with a variety of substrates and reagents to produce a library of different substituted trans-stilbenes, which revealed the method to hold a very good tolerance for an assortment of functional groups. The final synthetic route was successfully scaled-up (from mg scale) and performed in a 150 g (>1000×up-scaled) batch run to obtain an overall yield of 73 % (over three steps), which corresponds to a mean step yield of 90 %. The inhibitor candidate DC10 [(E)-5-(2-([1,1′-biphenyl]-4-yl)vinyl)-2-hydroxy-benzoic acid] was produced in multi-gram quantities (≈33 g) that subsequently was forwarded for animal efficacy and toxicology studies. The scaled-up process constitutes the first example of an oxidative Heck cross-coupling on >100-gram scale.

Nature Catalysis, Published online: 01 July 2021; doi:10.1038/s41929-021-00642-w

Despite its biocidal properties, the use of hydrogen peroxide is still limited in the context of water disinfection. Here an approach is disclosed based on the generation of H2O2 in situ by means of an AuPd catalyst, which can compete with chlorination methods by generating a highly reactive radical flux.

Publication date: 8 July 2021

Source: Chem, Volume 7, Issue 7

Author(s): Jian Sun, Hendrik Verplancke, Julia I. Schweizer, Martin Diefenbach, Christian Würtele, Matthias Otte, Igor Tkach, Christian Herwig, Christian Limberg, Serhiy Demeshko, Max C. Holthausen, Sven Schneider

ICP-MS is used to identify the unique mineral recipe used by Antonio Stradivari to treat his spruce wood, the material for the violin top plate. Chemical manipulation led to hemicellulose fragmentation and cellulose rearrangement. Incorporating engineered wood may contribute to the unique tonal qualities of these acclaimed instruments.

Abstract

We investigated the material properties of Cremonese soundboards using a wide range of spectroscopic, microscopic, and chemical techniques. We found similar types of spruce in Cremonese soundboards as in modern instruments, but Cremonese spruces exhibit unnatural elemental compositions and oxidation patterns that suggest artificial manipulation. Combining analytical data and historical information, we may deduce the minerals being added and their potential functions—borax and metal sulfates for fungal suppression, table salt for moisture control, alum for molecular crosslinking, and potash or quicklime for alkaline treatment. The overall purpose may have been wood preservation or acoustic tuning. Hemicellulose fragmentation and altered cellulose nanostructures are observed in heavily treated Stradivari specimens, which show diminished second-harmonic generation signals. Guarneri's practice of crosslinking wood fibers via aluminum coordination may also affect mechanical and acoustic properties. Our data suggest that old masters undertook materials engineering experiments to produce soundboards with unique properties.

Nature Chemistry, Published online: 28 June 2021; doi:10.1038/s41557-021-00733-y

Regioselective chemical modification of wild-type proteins remains challenging. Now, by harnessing the varied SOMOphilicity of native tyrosine residues through photoredox catalysis, a site-selective bioconjugation method has been developed. This technology directly incorporates bioorthogonal formyl groups in one step, forming structurally defined fluorescent conjugates that can be rapidly diversified to biorelevant products.

Nature, Published online: 28 June 2021; doi:10.1038/d41586-021-01751-z

Too few resources exist to help early-career scientists deal with the stresses encountered in today’s ‘publish or perish’ culture.