Synlett最新文献

π-Stacking is common in materials, but different π–π stacking modes remarkably affect the properties and performances of materials. In particular, weak interactions, π-stacking and hydrogen bonding often have a significant impact on the stability and sensitivity of high-energetic compounds. A fused [5,7,5]-tricyclic energetic compound with a conjugated structure has been designed and synthesized. 4H-[1,2,5]Oxadiazolo[3,4-e][1,2,4]triazolo[3,4-g][1,2,4]triazepin-8-amine is obtained in 48% yield from 3-amino-4-carboxy-1,2,5-oxadiazole through an efficient two-step reaction. Owing to its layered planar structure and weak π interactions between layers, 4H-[1,2,5]oxadiazolo[3,4-e][1,2,4]triazolo[3,4-g][1,2,4]triazepin-8-amine exhibits high thermal stability (T_d = 318 °C), low sensitivity (IS = 40 J, FS = 360 N), and relatively excellent detonation performance (D = 7059 ms^–1, P = 20.2 GPa). This detonation performance is superior to that of the conventional explosive TNT. The developed procedure provides a new method for the synthesis of fused ring compounds.

We propose a synthetic process for the preparation of a benzoxazole building block for a programmed death-ligand 1 inhibitor that is a candidate currently under clinical investigation for cancer treatment. Our research focused on searching for mild, scalable, and ecofriendly conditions for the synthesis of benzoxazoles. To reduce the use of toxic reagents or solvents and to minimize the production of organic wastes, the cyclization reaction was performed in an aqueous micellar medium. This in-water benzoxazole synthesis gave comparable yields to previously reported processes, and was applied to a broad range of benzoxazoles with various substitution patterns, showcasing its effectiveness in ecofriendly benzoxazole cyclization reactions.

A highly regioselective synthesis of allylic amines based on a tungsten-catalyzed allylic amination has been developed. This protocol, which is catalyzed by commercially available W(CO)₃(MeCN)₃ and 4,4′-di-tert-butyl-2,2′-bipyridine, permits the formation of synthetically useful branched allylic N-aryl- and N-alkylamines in moderate to good yields with a >20:1 branched/linear ratio under mild conditions. The noble-metal-free catalytic system complements conventional allylic aminations catalyzed by an Ir or Rh complex.

We report the first example of an acid- and oxidant-free one-pot conversion of benzylic or primary alkyl halides into aldehydes by using simple ruthenium chloride as the catalyst. The developed synthetic strategy is pot-economical and is also cheap as it uses hexamethylenetetramine as a reagent, employs as little as 0.5 mol% of ruthenium chloride, and efficiently converts the benzylic or primary alkyl halides into aldehydes in aqueous medium. The methodology was also found to be highly selective, as it forms the aldehyde product exclusively without forming possible byproducts, namely amines or carboxylic acids. The methodology is also superior in comparison with the conventional Sommelet and Kornblum oxidation reactions as it avoids the use of excess acid or DMSO, and uses very cheap and ecofriendly hexamethylenetetramine as both the formylating agent and base. The recyclability of the developed catalyst system was also tested, and showed excellent activities for up to three cycles.

A new method for the preparation of 3-hydroxy-4-methoxypicolinic acid, the acid moiety of the fungicidally active natural product UK-2A is reported. In contrast to the two previously reported routes to UK-2A acid, which start from 3-hydroxypyridine and furfural, this novel synthesis applies maltol as inexpensive starting material and proceeds via a unique modification of the Pummerer reaction.

We recently achieved an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins through the utilization of a new Gluconobacter ene-reductase mutant (GluER-W100F-W342F). Our method simplifies the reaction system by eliminating the need for a cofactor regeneration mixture and, in contrast with previous photoenzymatic systems, does not depend on the formation of an electron donor–acceptor (EDA) complex between the substrates and enzyme cofactor. Moreover, the GluER variant exhibits good substrate compatibility and excellent enantioselectivity. Mechanistic investigations indicate that a tyrosine-mediated HAT process is involved and support the proposed oxidation-initiated mechanism. In this Synpacts article, we discuss the conceptual framework that led to the discovery of this reaction and reflect on the key aspects of its development.

1 Introduction

2 Conceptual Background

2.1 Intramolecular Photoenzymatic Reactions via Single-Electron Reduction

2.2 Intermolecular Photoenzymatic Reactions via Single-Electron Reduction

3 The Development of the Process

4 Conclusion

An efficient Michael addition of 4-hydroxycoumarins to α,β-unsaturated 2-acyl imidazoles catalyzed by Ni(OTf)₂ as a Lewis acid has been developed. A series of 4-hydroxycoumarin derivatives were obtained in excellent yields (up to 96%) with a 2 mol% catalyst loading under mild conditions. Additionally, when a chiral-at-metal rhodium complex was used as the catalyst, moderate enantioselectivity was observed (74% ee).

In this study, we proposed a novel electrochemical dehydrogenative synthetic method for preparing 2-substituted quinoxalines by intermolecular cyclization of aryl alkyl ketones and o-phenylenediamines. This method gave various quinoxalines in yields ranging from 35% to 71%. This novel protocol employs mild reaction conditions and offers moderate to excellent yields, a wide substrate scope, and broad functional-group compatibility. Furthermore, a late-stage functionalization and the wide substrate scope demonstrated the synthetic utility of this protocol.