Synlett

A concise and efficient intramolecular oximation enables the rapid and streamlined synthesis of 2-isoxazolines. This metal-free approach offers a broad substrate scope under mild reaction conditions. The successful demonstration of gram-scale and one-pot synthesis highlights both the versatility and scalability of the method. The synthetic utility of this method is further exemplified by converting 2-isoxazolines into β-hydroxy ketones. This method was further used for the synthesis of firefly luciferase inhibitors.

A highly chemoselective consecutive cross-coupling/cyclization cascade of β-ketothioamides with dihaloalkanes has been achieved under transition-metal free condition, enabling the formation of methylene-functionalized thiazolidines and 1,3-thiazinanes at room temperature in open air in high yields. The typical features of this straightforward sustainable approach include readily accessible starting materials, simple one-pot operation, atom-/step-economy, cost-effective, good substrate scope, and scalability. Noteworthy, HX is the only by-product, and stereochemistry of the exocyclic methylene moiety was assigned to have Z-configuration. Late-stage functionalization could provide new opportunities for the discovery of N, S-heterocyclic drugs, and other potential functional molecules.

SynlettDOI: 10.1055/a-2744-3288Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents  |  Full text

For centuries, it appeared that the solvent was essential for conducting chemical experiments. It is widely accepted that solvent enables reactions to occur more efficiently. However, can solvents really enhance the efficiency of chemical reactions? To address this inquiry, we conducted this study. We examined 22 classic organic chemical reactions across 7 major categories. All reactions were divided into two parallel groups. In these two groups of experiments, except for the presence or absence of solvents, all other conditions were kept identical. The 537 data show that the yield fluctuation range in these two cases is: −13% to 19%. Based on these datasets, we draw the following conclusions: 1) The presence or absence of an excess solvent exerts minimal influence on the efficiency of most organic thermochemical reactions. 2) When one of the reactants is in liquid or gaseous state, the difference in reaction efficiency between completely solvent-free and solvent conditions is not significant. 3) When the reaction rate is relatively slow under conditions where all reactants are solid and there is no solvent at all, adding one to several equivalent amount of solvent can be comparable to the efficiency under conditions of a large amount of solvent.

A one-pot synthesis of 1-alkoxyisoquinolines via ruthenium(II)-catalyzed aryl C−H activation and annulation with internal alkynes has been demonstrated. The reaction involves in situ generation of a benzimidate ester by the addition of nucleophilic alcohols and it acts as an “automatic directing group” (DGauto) for the aryl C−H activation and subsequent alkyne annulation. In contrast to conventional nitrogen-containing DG-assisted annulation approaches, this DGauto-assisted annulation of alkynes via C−H activation is advantageous as it reduces the number of reaction steps, simplifies the experimental procedure, and allows for easier handling of the corresponding precursors. Based on preliminary experimental observations, a plausible mechanism is disclosed for this transformation. Interestingly, most of the compounds show intense fluorescence emission, and their absorption and emission spectra are also presented in this work.

Alkyne is one of the most exploited synthetic equivalent in organic synthesis due to easy accessibility and electron-rich nature. Subsequently, their excellent coordinating ability with metals make them an indispensable synthon in organic reactions. Notably, alkynes directly attached to a heteroatom (N, O, S) at C–C triple bond end have emerged as an alternative class of reactant that are able to generate structural diversity. In this context, ynamides where one end of C–C triple bond is attached with an amide unit have emerged as a versatile building blocks in chemical transformations over the past 20 years. The natural polarization of C–C triple bond in ynamides mobilizes a broad spectrum of chemical transformations under both metal-catalyzed and metal-free conditions. Few interesting review articles on ynamide chemistry have been appeared recently that cover synthetic potential and mechanistic insights. However, this review highlights the application potential of ynamides and bisynamides chemistry for the synthesis of aromatic N-heterocycles such as isoquinolines, quinolines, pyrroles, pyrrolo[2,3-b]quinolines, and diaryl[c,h][1,6]naphthyridines through metal-catalyzed cycloisomerization, annulation, and skeletal editing strategies, respectively. We have further shown that how ortho substitution in anilines yields different N-heterocycles upon varying reaction conditions. Notably, we have mostly used inexpensive and earth abundant metal salts for transformations.

Functionalized benzimidazoles are produced through a three-component reaction that combines phenylenediamine-1,3-dicarbonyl adducts, terminal alkynes, and phenylsulfonyl azide. This synthesis involves the generation of N-sulfonylketenimine intermediates via a copper-catalyzed azide-alkyne cycloaddition, which is subsequently followed by cyclization with the phenylenediamine-1,3-dicarbonyl adducts. The method is noted for its efficiency and versatility across a range of substrates, with the final compound’s structure being validated through single-crystal X-ray analysis.

Two derivatives of chiral trans-2-biphenyloxycyclohexanol were screened as chiral auxiliaries for the α-alkylation of aryloxypropanoic acids to obtain enriched enantiomers. The chiral auxiliary controls the enantioselective formation of α-aryloxypropanoic acids by dynamic kinetic resolution. The 2-phenylphenoxy derivative was found to be more effective in controlling chirality in the product as compared to its 4-phenylphenoxy isomer. Formation of the major isomer is supported by the calculation of their relative energies by computational analysis, using Gaussian 16.0 B3LYP/6-31+G(d) as a basis set.

The asymmetric intramolecular C–H insertion of an in situ generated diazoimine intermediate derived from N-tosyl-1,2,3-triazoles was investigated. Among the chiral paddlewheel dirhodium(II) complexes screened, only C
2-symmetric-like dirhodium(II) carboxylate complexes bearing axially chiral amino acid derivatives as ligands proved to be effective in asymmetric induction. This catalyst afforded 2,3-disubstituted tetrahydrofurans with reasonable enantioselectivity for the cis-isomer.

A unified strategy for the asymmetric total synthesis of streptoglycerides A and B has been established and has confirmed their proposed absolute configurations. Key to our strategy is the synthesis of a bicyclic scaffold, employing a gold-catalyzed cascade cyclization of 1,6-diyn-ol operating through a 6-endo/5-exo-dig mechanism and its one-pot dihydroxylation followed trans-glycosylation to forge the central tricyclic core of these natural products. Noyori’s asymmetric transfer hydrogenation of an α, β-acetylenic ketones has been employed to install the key propargyl alcohol center with the desired absolute configuration. The pendant conjugated trans-1,3,5-triene/trans-1,3-diene side chains were introduced from a propanaldehyde unit following [Pd]-catalyzed oxidative dehydrogenation, Takai olefination, and Stille cross-coupling.