Jia-Chen Xiang

Molecular Iodine-Mediated Chemoselective Synthesis of Multisubstituted Pyridines through Catabolism and Reconstruction Behavior of Natural Amino Acids

A new process has been developed for the selective construction of 2,6-disubstituted, 2,4,6-trisubstituted, and 3,5-disubstituted pyridines based on the catabolism and reconstruction behaviors of amino acids. Molecular iodine was used as a tandem catalyst to trigger the decarboxylation-deamination of amino acids and to promote the subsequent formation of the pyridine products.

Direct Synthesis of Substituted Naphthalenes from 1,3-Dicarbonyl Compounds and 1,2-Bis(halomethyl)benzenes Including a Novel Rearrangement Aromatization of Benzo[c]oxepine

An unexpected rearrangement aromatization of benzo[c]oxepine has been revealed to synthesize substituted naphthalenes. This observation was further exploited to develop an efficient approach for the construction of naphthalenes from simple and commercially available 1,3-dicarbonyl compounds and 1,2-bis(halomethyl)benzene compounds via a new domino reaction sequence.

Direct Construction of 4-Hydroxybenzils via Para-Selective C–C Bond Coupling of Phenols and Aryl Methyl Ketones

A highly para-selective C-C bond coupling is presented between phenols C(sp(2)) and aryl methyl ketones C(sp(3)), which enables the direct construction of 4-hydroxybenzil derivatives. This practical method exhibits a broad substrate scope and large-scale applicability and represents a general gateway to the hydroxybenzil natural product family. Mechanistic investigations indicated that the combination of HI with DMSO realized the oxidative carbonylation of aryl methyl ketones, while boric acid acted as a dual-functional relay reagent to promote this transformation.

Synthesis of 2,4,5-Trisubstituted Furans via a Triple C(sp3)–H Functionalization Reaction Using Rongalite as the C1 Unit

A highly efficient I2/Cu(NO3)2·3H2O-mediated triple C(sp(3))-H functionalization reaction for the synthesis of 2,4,5-trisubstituted furans from aryl methyl ketones and rongalite by employing rongalite as a C1 unit has been developed. This method allows rapid access to (2-acyl-4-methylthio-5-aryl) furans. Preliminary mechanistic studies indicate that in situ generated dimethyl(phenacyl)-sulfonium iodine and HCHO were probably the key intermediates in this transformation.

Divergent Synthesis of Functionalized Quinolines from Aniline and Two Distinct Amino Acids

A practicable quinoline synthesis from aniline and two amino acids was developed for generating a wide range of quinolines with high efficiency and diversity. Thus, it facilitated the creations of pharmaceutical derivatives, photochemical active compounds, and challenging scaffolds. The concept of using two amino acids as heterocyclic precursors has been raised for the first time. Mechanistic studies revealed that I2 enabled decarboxylation, oxidative deamination, and selective reconstruction of new C-N and C-C bonds processes.

Dimeric packing of molecular clips induced by interactions between π-systems

In order to investigate the self-association of asymmetric glycoluril clips, compounds 1–7 with a common p-dimethoxy-o-xylylene ring sidewall were synthesized and their structures were analyzed by X-ray crystallography. As expected, the clip molecules formed dimers promoted by π–π interactions between their aromatic sidewalls. Interestingly, the nature of the substituents on the differentially substituted sidewall caused appreciable differences in the observed dimerization motifs in the crystalline state. For example, 1 and 2 adopted the out–out dimeric motif with its diaromatic-vinyl-o-xylylene rings bound in the cleft of the neighboring molecular clip by π–π stacking interactions. In contrast, compounds 3–7 adopted the in–in dimeric motif in the solid state, in which the p-dimethoxy-o-xylylene rings were sandwiched by the adjacent clip driven by π–π and OCH3⋯OC H-bonding interactions. X-ray crystallographic analysis of compounds 1–7 indicates that the conformational preferences induced by the linking group between the o-xylylene sidewalls and the terminal aromatic rings plays a critical role in determining which mode of dimerization (in–in versus out–out) and three dimensional packing predominates. The ability to control the selective dimerization of asymmetric glycoluril derived molecular clips via π–π interactions promises to expand the use of these building blocks to design complex and functional solid state architectures.

Robust R22(8) hydrogen bonded dimer for crystal engineering of glycoluril derivatives

A series of glycoluril derivatives 1–3 were examined through crystallographic characterization to reveal a highly conserved amide⋯amide homosynthon, with intermolecular R22(8) hydrogen bonding interactions. As expected, the intermolecular hydrogen bonding interactions promoted the dimerization of the building blocks 1–3, even in the presence of competing pyridine rings and various solvent molecules. These robust dimer synthons were then connected to form a one-dimensional chain through C–H⋯O interactions and further extended to a two-dimensional layer by additional C–H⋯π interactions. This robust hydrogen bond motif was achieved without interference from competing intermolecular interactions and significant changes in the hydrocarbon core, and as such has much potential for application as a supramolecular synthon for solid-state design.

X-ray studies of conformation: observation of conformational polymorphism of a glycoluril clip

In order to study the conformational behavior of a glycoluril clip, compound 1 was synthesized and X-ray crystallography, NMR spectroscopy, and molecular modeling were used in the work. The results of the computational studies revealed the stability of the four conformers retained the order aa > as ≈ sa > ss in both gas and solvation models, while solvation decreased the relative energies of each conformer dramatically. In the solid phase, X-ray crystallographic analysis indicated that compound 1 presented conformational polymorphism when it crystallized in various solvents. We fortunately obtained a single crystal of the aa and as conformers of the same glycoluril clip. The X-ray crystallographic analysis in this report provides the first crystallographic evidence of the conformers of a glycoluril clip. Unlike in the solid state, the conformers interconvert rapidly in solution and therefore cannot be detected on the NMR timescale.

Oxidative Trimerization of Amino Acids: Selective Synthesis of 2,3,5-Trisubstituted Pyridines

An oxidative trimerization of three amino acids has been realized to furnish 2,3,5-trisubstuitued pyridines in both cross- and homo-trimerization types. This method is capable of converting simple linear biomass material to heterocycles, which features in the assembly of three amino acid branched chains into one aromatic ring. Molecular iodine triggers the sequential decarboxylation and deamination of amino acids and then promotes the selective formation of new C-N and C-C bonds.

C(sp3)-H Bond Functionalization of Benzo[c]oxepines via C-O bond Cleavage: Formal [3+3] Synthesis of Multi-Substituted Chromans

An efficient base-promoted C(sp3)-H bond functionalization strategy for the synthesis of multisubstituted chromans from the formal [3+3] cycloaddition of benzo[ c]oxepines and electron-rich phenols has been developed. The corresponding 4 H-chromenes can be easily obtained in excellent yields by simple filtration from chromans. Preliminary mechanistic studies indicate that the C-O bond cleavage is the key step for the C(sp3)-H bond functionalization and that this reaction could have occurred through tandem C-O bond cleavage/Michael addition/annulation reactions.