LongLarf

Nature, Published online: 09 October 2019; doi:10.1038/s41586-019-1616-2

It's never too late: The conversion of primary sulfonamides into sulfonyl chlorides has been achieved by capitalizing on the use of Pyry‐BF₄ as activating reagent. The mild reaction conditions and high selectivity of the protocol permit the presence of a preponderance of functional groups and the conversion of poorly nucleophilic and unreactive sulfonamides for late‐stage functionalizations.

Abstract

Reported here is a simple and practical functionalization of primary sulfonamides, by means of a pyrylium salt (Pyry‐BF₄), with nucleophiles. This simple reagent activates the poorly nucleophilic NH₂ group in a sulfonamide, enabling the formation of one of the best electrophiles in organic synthesis: a sulfonyl chloride. Because of the variety of primary sulfonamides in pharmaceutical contexts, special attention has been focused on the direct conversion of densely functionalized primary sulfonamides by a late‐stage formation of the corresponding sulfonyl chloride. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides, sulfonates, sulfides, sulfonyl fluorides, and sulfonic acids. The mild reaction conditions and the high selectivity of Pyry‐BF₄ towards NH₂ groups permit the formation of sulfonyl chlorides in a late‐stage fashion, tolerating a preponderance of sensitive functionalities.

A one‐pot multi‐step method for the oxidative cleavage of alkenes to aldehydes/ketones under ambient conditions is reported. Combining a highly efficient manganese catalyzed epoxidation/cis‐dihydroxylation with Fe(III)(ClO₄)₃ assisted ring opening is followed by periodiate cleavage of the resulting diol.

A one‐pot multi‐step method for the oxidative cleavage of alkenes to aldehydes/ketones under ambient conditions is described as an alternative to ozonolysis. The first step is a highly efficient manganese catalyzed epoxidation/cis‐dihydroxylation of alkenes. This step is followed by an Fe(III) assisted ring opening of the epoxide (where necessary) to a 1,2‐diol. Carbon–carbon bond cleavage is achieved by treatment of the diol with sodium periodate. The conditions used in each step are not only compatible with the subsequent step(s), but also provide for increased conversion compared to the equivalent reactions carried out on the isolated intermediate compounds. The described procedure allows for carbon–carbon bond cleavage in the presence of other alkenes, oxidation sensitive moieties and other functional groups; the mild conditions (r.t.) used in all three steps make this a viable general alternative to ozonolysis and especially for use under flow or continuous batch conditions.

Nature, Published online: 08 October 2019; doi:10.1038/d41586-019-03020-6

Synlett
DOI: 10.1055/s-0039-1690988

An original metal-free regio- and stereoselective intermolecular hydroamination of alkynes is described. Various (E)-enamines were obtained from arylacetylenes and aliphatic secondary amines in the presence of ethylene glycol as a solvent. The latter is assumed to play a major role in the mechanism through hydrogen bonding and proton exchange.
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© Georg Thieme Verlag Stuttgart · New York

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News on NP₃ ring systems: The reactivity of chlorinated NP₃ ring systems was investigated by experimental and computational methods. Comparisons with known N₂P₂ and P₄ congeners are drawn to obtain a systematic understanding of the reactivity of these types of compounds.

Abstract

The reactivity of the four‐membered NP₃ ring system [RN(μ‐PCl)₂PR] (R=Mes*=2,4,6‐tri‐tert‐butylphenyl) towards Lewis acids, Lewis bases, and reducing agents was investigated. Comparisons with the literature‐known, analogous cyclic compounds [ClP(μ‐NR)]₂ (R=Ter=2,6‐dimesitylphenyl) and [ClP(μ‐PR)]₂ (R=Mes*) are drawn, to obtain a better systematic understanding of the reactivity of cyclic NP species. Apart from experimental results, DFT computations are discussed to further the insight into bonding and electronic structure of these compounds.

Nature Catalysis, Published online: 07 October 2019; doi:10.1038/s41929-019-0357-9

Publication date: 8 November 2019

Source: Tetrahedron, Volume 75, Issue 45

Author(s): Sven Klare, Jonathan P. Gordon, Andreas Gansäuer, T.V. RajanBabu, William A. Nugent

Graphical abstract

Nature, Published online: 02 October 2019; doi:10.1038/s41586-019-1589-1

Raising alkaloids: A flexible synthesis of indolizidine and quinolizidine alkaloids is facilitated by stereoselective conversions of vinyl cyclic carbonates under Pd catalysis into key stereodefined homoallylic nitroalkane intermediates. The vinyl cyclic carbonate substrates are showcased as modular and accessible reagents useful in natural product synthesis (see scheme).

Abstract

Cyclic carbonates have long been considered relatively inert molecules acting as protecting groups in complex multistep synthetic routes. This study shows that a concise, yet modular synthesis of indolizidine and quinolizidine alkaloids can be developed from vinyl‐substituted cyclic carbonate (VCC) intermediates. Through a highly stereoselective palladium‐catalyzed allylic alkylation reaction, these alkaloid motifs can be assembled in four synthetic and only two column purification steps. The combined results help to further advance functionalized cyclic carbonates as useful and reactive intermediates in natural product synthesis.

Come together: A highly reactive silylium ion brings together two unreactive reactants while being consumed and regenerated during the catalytic cycle. Unactivated alkenes are thus converted into 1,2‐bissilylated alkanes using simple hexamethyldisilane. The Si−Si bond is cleaved during this process in a kinetically and thermodynamically favored 1,3‐silyl shift from silicon to carbon, as supported by quantum‐chemical calculations.

Abstract

A metal‐free, intermolecular syn‐addition of hexamethyldisilane across simple alkenes is reported. The catalytic cycle is initiated and propagated by the transfer of a methyl group from the disilane to a silylium‐ion‐like intermediate, corresponding to the (re)generation of the silylium‐ion catalyst. The key feature of the reaction sequence is the cleavage of the Si−Si bond in a 1,3‐silyl shift from silicon to carbon. A central intermediate of the catalysis was structurally characterized by X‐ray diffraction, and the computed reaction mechanism is fully consistent with the experimental findings.

Nature Communications, Published online: 01 October 2019; doi:10.1038/s41467-019-12189-3

Synlett
DOI: 10.1055/s-0039-1690691

Organic azides serve as synthetically useful surrogates for primary amines, a functional group which is ubiquitous in bioactive and medicinally relevant molecules. Historically, the formal hydroazidation of simple activated olefins and styrenes has proven difficult due to the inherent propensity of these compounds to oligomerize. Herein is disclosed a method for the anti-Markovnikov hydroazidation of activated olefins, catalyzed by an organic acridinium salt under irradiation from blue LEDs. This method is applicable to a variety of substituted and terminal styrenes and several vinyl ethers, yielding synthetically versatile hydroazidation products in moderate to excellent yield.
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© Georg Thieme Verlag Stuttgart · New York

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All metal‐free: A photoinduced tandem amine dehydrogenation/Povarov cyclization/aromatization reaction leads to isocryptolepine analogues with high yields, by using molecular iodine under visible light, or by combining an organic photoredox catalyst with a halide anion (see scheme; PC=photocatalyst).

Abstract

A metal‐free, photoinduced aerobic tandem amine dehydrogenation/Povarov cyclization/aromatization reaction between N‐aryl glycine esters and indoles leads to tetracyclic 11H‐indolo[3,2‐c]quinolines under mild conditions and with high yields. The reaction can be performed by using molecular iodine along with visible light, or by combining an organic photoredox catalyst with a halide anion. Mechanistic studies reveal that product formation occurs through a combination of radical‐mediated oxidation steps with an iminium ion or N‐haloiminium ion [4+2]‐cycloaddition, and the N‐heterocyclic products constitute new analogues of the antiplasmodial natural alkaloid isocryptolepine.

Nature, Published online: 25 September 2019; doi:10.1038/s41586-019-1580-x