First Exclusive Stereo- and Regioselective Preparation of 5-Arylimino-1,3,4-Selenadiazole Derivatives: Synthesis, NMR analysis, and Computational Studies.

Isoselenocyanates are valuable coupling partners required for preparing key chemical intermediates and biologically active molecules in an accelerated and effective way. Likewise, (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides have been employed in numerous one-step heteroannulation reactions to assemble the structural core of several various kinds of heterocyclic compounds. Here, we describe the inverse electron demand 1,3-dipolar cycloaddition reaction of isoselenocyanates with a variety of substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides to generate, regioselectively and stereoselectively, a series of 5-arylimino-1,3,4-selenadiazole derivatives comprising a multitude of functional groups on both aryl rings. The synthetic method features gentle room-temperature conditions, wide substrate scope, and good to high reaction yields. The selenadiazoles were separated by gravity filtration in all instances and chemical structures were validated by multinuclear NMR spectroscopy and high accuracy mass spectral measurements. First conclusive molecular structure elucidation of the observed 5-arylimino-selenadiazole regioisomer was verified by single-crystal X-ray diffraction analysis. Crystal-structure measurement was successfully carried out on (Z)-1-(4-(4-iodophenyl)-5-(p-tolylimino)-4,5-dihydro-1,3,4-selenadiazol-2-yl)ethan-1-one and (Z)-1-(5-((4-methoxyphenyl)imino)-4-(4-(methylthio)phenyl)-4,5-dihydro-1,3,4-selenadiazol-2-yl)ethan-1-one. Likewise, the (Z)-geometry of the hydrazonoyl chloride reactant was proven by X-ray diffraction studies. As representative examples, crystal-structure determination was carried out on (Z)-2-oxo-N-phenylpropanehydrazonoyl chloride and (Z)-N-(3,5-bis(trifluoromethyl)phenyl)-2-oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP-D4/def2-TZVP level were conducted to support the noted experimental findings and suggested mechanism.

A Practical Synthesis of Densely Functionalized Pyrroles via a Three-Component Cascade Reaction between Carbohydrates, Oxoacetonitriles, and Ammonium Acetate.

A practical three-component reaction between unactivated carbohydrates, oxoacetonitriles, and ammonium acetate gave densely functionalized pyrroles in 75-96% yields. Disaccharides afforded novel pyrrolo-glycosides. This metal-free, Et3N-catalyzed cascade reaction proceeded with exclusive chemo-, regio-, and stereoselectivities and showed a wide substrate scope with high atom economy. It also proceeded successfully at a 2 g scale, demonstrating potential for large-scale synthesis. The functional groups on the pyrroles permit easy transformation to other handles for the construction of more complex structures. The reaction proceeded through a cascade mechanism involving several intermediates identified by mass spectrometric analysis. This work has great potential for the sustainable production of densely functionalized pyrroles from cheap and widely available carbohydrates and represents a key advancement in the sustainable synthesis of these ubiquitous heterocycles.

TMSOTf-Promoted Intermolecular Cascade Reaction of Aromatic Diazo Ketones with Olefins: Selective Synthesis of 3-Arylethylideneoxindoles.

A simple trimethylsilyl trifluoromethanesulfonate (TMSOTf)-promoted intermolecular cascade reaction of aromatic diazo ketones with olefins has been developed. This method directly gave 3-phenylethylideneoxindoles from 3-diazooxindoles and styrenes with exclusive regioselectivity, chemoselectivity, and E-stereoselectivity. The key to the success of the reaction and higher yields is the elegant use of TMSOTf, which gradually released the active triflic acid promoter in situ. The reaction tolerates a wide substrate scope of 3-diazooxindoles and styrenes with electron-donating and electron-withdrawing groups and works well on the gram scale.

Perfluorophenylboronic acid-catalyzed direct α-stereoselective synthesis of 2-deoxygalactosides from deactivated peracetylated d-galactal.

Perfluorophenylboronic acid 1c catalyzes the direct stereoselective addition of alcohol nucleophiles to deactivated peracetylated d-galactal to give 2-deoxygalactosides in 55-88% yield with complete α-selectivity. The unprecedented results reported here also enable the synthesis of disaccharides containing the 2-deoxygalactose moiety directly from the deactivated peracetylated d-galactal. This convenient and metal-free glycosylation method works well with a wide range of alcohol nucleophiles as acceptors and tolerates a range of functional groups without the formation of the Ferrier byproduct and without the need for a large excess of nucleophiles or additives. The method is potentially useful for the synthesis of a variety of α-2-deoxygalactosides.

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides.

A convenient protocol was developed for the synthesis of 2,3-unsaturated C-, O-, N- and S-linked glycosides (enosides) using 20 mol % perflurophenylboronic acid catalyst via Ferrier rearrangement. Using this protocol, D-glucals and L-rhamnals reacted with various C-, O-, N- and S-nucleophiles to give a wide range of glycosides in up to 98% yields with mainly α-anomeric selectivity. The perflurophenylboronic acid successfully catalyzed a wide range of substrates (both glucals and nucleophiles) under very mild reaction conditions.

Construction of Fused Oxabicyclic Scaffolds from Glycals and Styrenes via One-Pot Domino Transformations.

Triflic acid catalyzed cascade stereoselective reaction of glycals with styrenes delivers complex oxabicyclic scaffolds such as cis-oxadecalins or cis-cyclopentanofurans simply by tweaking the solvent. In the presence of participating solvents like benzene/toluene, cascade Ferrier C-glycosylation and double Friedel-Crafts reaction leads to densely chiral benzo-fused oxadecalins, whereas in DCM, an unprecedented ring-opening, ring-closing sequence generated cis-cyclopentanofurans. An attempt has been made to explain the above cascade sequences via intermediate trapping, kinetic experiments, and Baldwin's rules.

Diastereoselective sp2-sp3 coupling of sugar enol ethers with unactivated cycloalkenes: new entries to C-branched sugars.

Sugar enol ethers undergo efficient coupling at C-2 with unactivated cycloalkenes under a low Pd loading affording allylic substitution products. High diastereoselectivity was observed at the allylic centre with sterically hindered substrates. Generation of a π-allyl complex by the Pd(ii) catalyst via cleavage of the allylic C-H bond of the cycloalkene may be responsible for the formation of sp2-sp3 coupling products.

Organo-zinc Promoted Diastereoselective C-Arylation of 1,2-Anhydrosugars from Arylboronic Acids.

α-C-arylglycosides can be obtained through the addition of aryl zinc reagents to sugar epoxides. The required aryl zinc nucleophiles can be easily obtained from the corresponding boronic acids by B-Zn exchange and attack sugar 1,2 epoxides in a highly diastereoselective fashion to generate 1,2-cis-α-hexapyranosyl aryl glycosides under ligand- and base-free conditions.

TEMPO-Promoted Domino Heck-Suzuki Arylation: Diastereoselective Cis-Diarylation of Glycals and Pseudoglycals.

A palladium-catalyzed regio- and diastereoselective diarylation of glycals and pseudoglycals, which is a kind of Heck-Suzuki arylation, is described. A wide range of arylboronic acids reacted under these conditions smoothly. Selectivity was C1-C2(α,α) in the case of glycals but C2-C3(ß,ß) for pseudoglycals. Quantum chemical analysis has been carried out to establish the reaction mechanism, which may involve Pd(II)/Pd(O). TEMPO plays a key role in the formation of diaryl glycoside due to its radical nature.

Zinc mediated activation of terminal alkynes: stereoselective synthesis of alkynyl glycosides.

Zinc mediated alkynylation reaction was studied for the preparation of C-glycosides from unactivated alkynes. Different glycosyl donors such as glycals and anomeric acetates were tested towards an alkynyl zinc reagent obtained from alkynes using zinc dust and ethyl bromoacetate as an additive. The method provides simple, mild and stereoselective access to alkynyl glycosides both from aromatic and aliphatic acetylenes.