Olefin skeletal rearrangement enabling access to multiarylated N-sulfonyl amidines.

A base-promoted olefin skeletal rearrangement strategy from para-quinone methides (p-QMs) and N-fluoroarenesulfonamides is reported, enabling direct nitrogen insertion of olefins to produce a series of multiarylated (Z)-N-sulfonyl amidines with complete stereoselectivity and generally good yields. Using p-QMs without o-hydroxy substituents gave triarylated N-sulfonyl amidines, whereas tetraarylated N,N'-disulfonyl amidines were synthesized with the existence of o-hydroxy groups.

Lewis Acid-Catalyzed Remote Site-Selective Ring Deconstruction of Cyclobuteno[a]naphthalene-4-ones to Access Unsymmetric 1,1-Diarylated Olefins.

A catalytic site-selective ring deconstruction of cyclobuteno[a]naphthalene-4-ones with alcohols is reported, enabling the direct production of a wide range of unsymmetric 1,1-diarylated olefins with good yields and complete regioselectivity. The late-stage application of these resulting terminal olefins demonstrates great possibilities to apply this strategy to complex molecules. The protocol features good functional group compatibility, broad substrate scope, and controllable site selectivity.

Organocatalytic Asymmetric [2 + 4] Cycloadditions of 3-Vinylindoles with ortho-Quinone Methides.

Catalytic asymmetric [2 + 4] cycloadditions of 3-vinylindoles with ortho-quinone methides and their precursors were carried out in the presence of chiral phosphoric acid to afford a series of indole-containing chroman derivatives with structural diversity in overall high yields (up to 98%), good diastereoselectivities (up to 93:7 dr) and moderate to excellent enantioselectivities (up to 98% ee). This approach not only enriches the chemistry of catalytic asymmetric cycloadditions involving 3-vinylindoles but is also useful for synthesizing chiral chroman derivatives.

Construction of chiral chroman scaffolds via catalytic asymmetric (4 + 2) cyclizations of para-quinone methide derivatives with 3-vinylindoles.

A catalytic asymmetric (4 + 2) cyclization of ortho-hydroxyphenyl-substituted para-quinone methide derivatives with 3-vinylindoles has been established in the presence of chiral phosphoric acid, which provides a series of chiral chroman derivatives bearing an indole moiety in generally high yields (up to 97%), and with good enantioselectivities (up to 90% ee) and moderate to good diastereoselectivities (up to 95 : 5 dr). This reaction has not only fulfilled the need of developing catalytic asymmetric (4 + 2) cyclizations of para-quinone methide derivatives with electron-rich alkenes, but also provided a useful method for constructing chiral chroman scaffolds.

Diastereo- and Enantioselective Construction of Biologically Important Chiral 1,3-Dioxolochroman Frameworks via Catalytic Asymmetric [4+2] Cycloaddition.

A diastereo- and enantioselective construction of biologically important chiral 1,3-dioxolochroman frameworks has been established via chiral phosphoric acid (CPA)-catalyzed asymmetric [4+2] cycloaddition of ortho-quinone methides with 3-methyl-2-vinylindoles. By using this approach, a series of indole-based chiral 1,3-dioxolochromans were synthesized with structural diversity in generally good yields, excellent diastereoselectivities and high enantioselectivities (up to 98% yields, >95:5 dr, 97% ee). The evaluation on the cytotoxic activity of some selected products indicated that this class of chiral 1,3-dioxolochroman derivatives had some extent of anti-cancer activity. This reaction not only provides an efficient synthetic method for accessing chiral 1,3-dioxolochroman derivatives with structural diversity and optical purity but also will enrich the research contents of catalytic asymmetric [4+2] cycloadditions involving ortho-quinone methides. In addition, the bioassay of these compounds will cast a light on discovering useful bioactivities of chiral 1,3-dioxolochroman derivatives, which will be helpful for finding lead compounds.

Diastereo- and Enantioselective Construction of the Hexahydrocoumarin Scaffold via an Organocatalytic Asymmetric [3 + 3] Cyclization.

The first catalytic asymmetric construction of the biologically important hexahydrocoumarin scaffold has been established, which takes advantage of chiral thiourea-tertiary amine-catalyzed enantioselective transformations. Besides, this reaction also realized the first catalytic asymmetric [3 + 3] cyclization of 4-arylidene-2-aryloxazol-5(4H)-ones with cyclohexane-1,3-diones, which afforded structurally diverse 3-aminohexahydrocoumarin derivatives in excellent diastereoselectivities and high enantioselectivities (all >95:5 dr, up to 96:4 er). The investigation on the activation mode suggested that the chiral thiourea-tertiary amine catalyst simultaneously activated the two substrates via hydrogen-bonding interaction. Moreover, this reaction could be applied to a large scale synthesis of enantioenriched hexahydrocoumarin. This approach will not only provide an efficient method for the construction of the chiral hexahydrocoumarin scaffold but also enrich the research areas of asymmetric organocatalysis and catalytic enantioselective [3 + 3] cyclizations.

Brønsted acid catalyzed asymmetric diels-alder reactions: stereoselective construction of spiro[tetrahydrocarbazole-3,3'-oxindole] framework.

The chiral phosphoric acid catalyzed asymmetric Diels-Alder reactions of 2-vinylindoles with methyleneindolinones have been established, which efficiently construct the spiro[tetrahydrocarbazole-3,3'-oxindole] architecture with one quaternary and three contiguous stereogenic centers in high yields (up to 99%) and excellent stereoselectivities (up to >95:5 dr, 97% ee). This reaction not only provides an efficient strategy to access enantioenriched spiro[tetrahydrocarbazole-3,3'-oxindoles] based on hydrogen-bonding activation mode but also supplies successful examples of catalytic asymmetric Diels-Alder reactions for constructing complex spiro-frameworks with optical purity.

Highly selective domino multicyclizations for forming polycyclic fused acridines and azaheterocyclic skeletons.

Highly selective four-component domino multicyclizations for the synthesis of new fused acridines and azaheterocyclic skeletons have been established by mixing common reactants in isobutyric acid under microwave irradiation. The reactions proceeded at fast rates and were conducted to completion within 20-30 min. Up to seven new chemical bonds, four rings, and four stereocenters were assembled in a convenient one-pot operation. The resulting hexacyclic and pentacyclic fused acridines and their stereochemistry have been fully characterized and determined by X-ray structural analysis.

Allylic amination and N-arylation-based domino reactions providing rapid three-component strategies to fused pyrroles with different substituted patterns.

New three-component domino reaction providing divergent approaches to multifunctionalized fused pyrroles with different substituted patterns have been established (40 examples). The direct C(sp(3))-N bond formation was achieved through intermolecular allylic amination in a one-pot operation, and N-arylation of amines was realized by varying N-amino acid enaminones. The reaction is easy to perform simply by mixing three common reactants in acetic acid under microwave heating. The reaction proceeds at fast rates and can be finished within 30 min, which makes workup convenient to give good chemical yields.

New domino heteroannulation of enaminones: synthesis of diverse fused naphthyridines.

A series of new poly-functionalized fused naphthyridine derivatives were synthesized via a three-component reaction of aldehyde, 2-aminoprop-1-ene-1,1,3-tricarbonitrile and enaminone in EtOH using EtONa as a base. During these reaction processes, the domino construction of fused naphthyridine skeleton with concomitant formation of two new pyridine rings was readily achieved via base promoted three-component reactions in a one-pot operation. The procedures are facile, avoiding time-consuming and costly syntheses, tedious work-up and purifications of precursors.