Mei-Xiang Wang

Brønsted Acid Catalyzed Enantioselective Three-Component Reaction Involving the α Addition of Isocyanides to Imines†

That a chiral phosphoric acid is able to catalyze the three-component reaction of aldehydes, anilines, and alpha -isocyanoacetamides, leading to 2-(1-aminoalkyl)-5-aminooxazoles in excellent yields and moderate to good enantioselectivities, was reported. [on SciFinder (R)]

Synthesis and Molecular Recognition of Water‐Soluble S6‐Corona[3]arene[3]pyridazines

We report the efficient and scalable synthesis and molecular-recognition properties of novel and water-soluble S6-corona[3]arene[3]pyridazines. The synthesis comprises a one-pot nucleophilic aromatic substitution reaction between diesters of 2,5-dimercaptoterephthalate and 3,6-dichlorotetrazine followed by the inverse electron-demand Diels-Alder reaction of the tetrazine moieties with an enamine and exhaustive saponification of esters. The resulting S6-corona[3]arene[3]pyridazines, which adopt a 1,3,5-alternate conformation in the crystalline state, are able to selectively form stable 1:1 complexes with dicationic guest species in water with association constants ranging from (1.10±0.06)×10(3)  M(-1) to (1.18±0.06)×10(5)  M(-1). The easy availability, large cavity size, strong and selective binding power render the water-soluble S6-corona[3]arene[3]pyridazines useful macrocyclic hosts in various disciplines of supramolecular chemistry.

Synthesis, structure, and fullerene-complexing property of azacalix[6]aromatics.

Synthesis, structure, and fullerene-binding property of azacalix[6]aromatics were systematically studied. By means of [3 + 3] and [2 + 2 + 2] fragment coupling protocols, a number of azacalix[6]aromatics containing different combinations of benzene, pyridine, and pyrimidine rings and various substituents on the bridging nitrogen atoms were synthesized conveniently in moderate to good yields. The resulting macrocycles adopt in the solid state symmetric and heavily distorted 1,3,5-alternate conformations depending on the aromatic building units, whereas, in solution, they exist as a mixture of conformers that undergo rapid interchanges relative to the NMR time scale. All macrocycles were able to form 1:1 complexes with C60 and C70 in toluene with the association constants up to 7.28 × 10(4) M(-1). In the crystalline state, azacalix[6]aromatics form complexes with C60 and C70 with 2:1, 1:1, and 1:2 stoichiometric ratios between host and guest. Azacalix[6]aromatics interact with fullerene by forming mainly the sandwich structure in which C60 or C70 is sandwiched by two macrocycles. X-ray molecular structures revealed that multiple π-π and CH-π interactions between concave azacalix[6]aromatics and convex fullerenes C60 and C70 contribute a joint driving force to the formation of host-guest complexes.

Catalytic Asymmetric Difunctionalization of Stable Tertiary Enamides with Salicylaldehydes: Highly Efficient, Enantioselective, and Diastereoselective Synthesis of Diverse 4-Chromanol Derivatives

Catalyzed by a chiral BINOL-Ti(OiPr)4 complex, various stable tertiary enamides reacted with salicylaldehydes to afford diverse cis,trans-configured 4-chromanols that contain three continuous stereogenic centers in good yields with excellent diastereoselectivity and enantioselectivity. The reaction proceeded through the addition of enamide to aldehyde followed by the intramolecular interception of the resulting iminium by the hydroxy group. Oxidation of the resulting 4-chromanols yielded almost quantitatively chroman-4-one derivatives which underwent diastereospecific reduction with NaBH4 to produce cis,cis-configured 4-chromanols.

Switchable [3+2] and [4+2] Heteroannulation of Primary Propargylamines with Isonitriles to Imidazoles and 1,6-Dihydropyrimidines: Catalyst Loading Enabled Reaction Divergence

Isonitrile 1 due to its carbene-like reactivity serves generally as a one-carbon synthon in a diverse set of organic transformations. We report in this article that the isocyano group can also act as a polarized triple bond to undergo, as a two-atom synthon, heteroannulation with primary propargylamines 15. In addition, we serendipitously discovered that the reaction pathways can be modulated by simply changing the catalyst loading. In the presence of 0.1 equiv of Yb(OTf)3 or TfOH, the reaction between 1 and 15 afforded exclusively imidazoles 16 by a formal [3+2] cycloaddition. At a higher catalyst loading (Yb(OTf)3 (0.4 equiv) or TfOH (0.5 equiv)) under otherwise identical conditions, the same reaction furnished 1,6-dihydropyrimidines 17 in good to excellent yields by way of a formal [4+2] cycloaddition process. Mechanistic investigations indicated that both annulations went through an amidine intermediate resulting from the insertion of the isocyano group to the NH bond of the primary amine. Subsequent catalyst-loading-dependent 5-exo-dig or 6-endo-dig cyclization provided selectively the two heterocycles, respectively.

Synthesis of Multifunctionalized 1,2,3,4-Tetrahydropyridines, 2,3-Dihydropyridin-4(1H)-ones, and Pyridines from Tandem Reactions Initiated by [5+1] Cycloaddition of N-Formylmethyl-Substituted Enamides to Isocyanides: Mechanistic Insight and Synthetic Application

Tandem reactions for the efficient synthesis of multifunctionalized 1,2,3,4-tetrahydropyridines, 2,3-dihydropyridin-4(1H)-ones, and pyridine derivatives have been developed and reaction mechanisms have been investigated. Synthetic cascades are initiated by the Zn(OTf)2-mediated [5+1] cycloaddition of N-formylmethyl-substituted tertiary enamides to isocyanides, thus leading to the versatile heterocyclic enamino imine intermediates. Interception of the intermediates by diastereoselective reduction of imine functionality with Me4NBH(OAc)3 afforded 1,6-disubstituted trans-3-hydroxy-4-arylamino- or -alkylamino-1,2,3,4-tetrahydropyridines, whereas acylation of the imino group followed by acidic hydrolysis produced 1,6-disubstituted 3-acyloxy-2,3-dihydropyridin-4(1H)-ones. Aerobic oxidation led to the aromatization followed by intermolecular acyl-group transfer from the pyridinium nitrogen to the 3-hydroxy moiety, thereby yielding substituted 3-acyloxy-4-aminopyridines. Synthetic potentials of the resulting products have been demonstrated by expedient and highly stereoselective synthesis of cis,cis-4,5-dihydroxy-2-phenylpiperidine and trans,trans-4-amino-5-hydroxy-2-phenylpiperidine compounds, which are important in medicinal chemistry, through simple and practical reduction reactions.

Dual templated synthesis of silver acetylide cluster-encapsulated supramolecular boxes

A dual-templated approach for the controllable synthesis of metal cluster complexes is described. By using an acetylide-containing anion with specific geometry as a central template and a macrocyclic coordinative compound as a peripheral one, two multinuclear silver-acetylide cluster-encapsulated supramolecular boxes were synthesized.

Practical biocatalytic desymmetrization of meso-N-heterocyclic dicarboxamides and their application in the construction of aza-sugar containing nucleoside analogs

Amidase-catalyzed desymmetrization of meso-N-heterocyclic dicarboxamides under very mild conditions provided a highly efficient and practical method for the preparation of enantiomerically pure carbamoyl-substituted heterocyclic amino acids that were unique and versatile platforms for the construction of both antipodes of aza-sugar containing nucleoside analogs.

Functionalized imidazoliniums from the three-component domino reaction of N-formylmethylcarboxamides with amines and isocyanides

In the presence of Zn(OTf)2, the three-component domino reaction of N-formylmethyl-substituted tertiary amides and enamides with amines and isocyanides in acetonitrile at room temperature produced functionalized imidazoliniums in good to excellent yields.

O6-Corona[6]arenes with Expanded Cavities for Specific Complexation with C70

O6-Corona[3]arene[3]tetrazines with expanded cavities were synthesized by one-pot SNAr reaction between 3,6-dichlorotetrazine and aromatic diols. The macrocycle-to-macrocycle transformation involving IEDDA of tetrazine moieties with an enamine followed by denitrogenative aromatization afforded O6-corona[3]arene[3]pyridazines. O6-Corona[6]arenes adopted coronary conformations yielding hexagonal cavities of varied sizes. While O6-corona[3]arene[3]pyridazines complexed both C60 and C70 in a virtually nonselective manner, O6-corona[3]arene[3]tetrazines behaved as selective receptors to complex C70 with K1:1 values up to (3.98 ± 0.08) × 104 M-1 in toluene.