Enantioselective Construction of Axially Chiral Azepine-Containing P,N-Ligands from l-Alanine.

A family of axially chiral azepine-containing seven-membered cyclic P,N-ligands (named Indole-azepinap) have been prepared by using l-alanine as an original chirality source. The direct chromatographic separation of two diastereomeric phosphine oxides on silica gel enabled these ligands to be easy available, allowing further structural and electronic modifications. Preliminary application of these Indole-azepinaps has been demonstrated in a Pd-catalyzed asymmetric allylic alkylation with high yields and moderate enantioselectivities.

High Chemo-/Stereoselectivity for Synthesis of Polysubstituted Monofluorinated Pyrimidyl Enol Ether Derivatives.

A novel intramolecular Smiles rearrangement of α-fluoro-β-keto-pyrimidylsulfones (usually used as a carbon nucleophile) was developed, providing a versatile avenue for synthesis of tri/tetra-substituted monofluorinated pyrimidyl enol ethers. Among these, diverse ()-monofluorovinylsulfones and sulfinates were efficiently assembled by adding extra electrophile and fine-tuning reaction conditions. The process is triggered by a keto-enol tautomerism from enol oxyanion to pyrimidine 2-carbon, completely different from the classical carbon nucleophilic addition reaction approach.

Enantioselective Construction of C-C Axially Chiral Quinazolinones via Chirality Exchange and Phase-Transfer Catalysis.

A family of axially chiral quinazolinone-based heterobiaryls were constructed with high levels of enantiocontrol (up to 94% ee). Convergently, three different synthetic methods have been realized to prepare these valuable compounds including central-to-axial chirality transfer, dynamic kinetic resolution, and phase-transfer catalysis. Importantly, novel P,N-ligands with a π-π stacking can be derived from heterobiaryls by chirality exchange strategy or synthesized directly from complementary phase-transfer catalysis by using the inexpensive chiral quaternary ammonium salt.

Enantioselective Construction of Quinoxaline-Based Heterobiaryls and P,N-Ligands via Chirality Transfer Strategy.

Central-to-axial chirality transfer via C-N single bond oxidation was first achieved as a versatile and conceptually distinct strategy to prepare a new family of axially chiral heteroaromatic biaryl backbones and P,N-ligands (named as Quinoxalinaps) in gram scale. Two atropisomers of Quinoxalinaps (ee >99%) were readily accessed from the same precursor enantiomer by a simple dehydrogenative oxidation with MnO and -BuOOH under mild conditions. Phosphine could be introduced into the ligands before or after the chirality control process.

Grignard-Reagent-Promoted Desulfonylation/Intramolecular Coupling for the Synthesis of 2-(1-Fluorovinyl)pyridines.

A novel process involving Grignard-reagent-promoted desulfonylation/intramolecular coupling of readily available α-fluoro-α,β-unsaturated-(2-pyridyl)sulfones was realized that provided a series of polysubstituted 2-(1-fluorovinyl)pyridines in good yields. The intrinsic coordination between pyridine and Mg(II) along with the "negative fluorine effect" of the substrates should play the key role for the smooth transformation in the absence of transition-metal catalysts.

Chiral Brønsted acid-catalyzed dynamic kinetic resolution of atropisomeric ortho-formyl naphthamides.

Despite the widespread use of naphthamide atropisomers in biologically active compounds and asymmetric catalysis, few catalytic methods have succeeded in the enantioselective synthesis of these compounds. Herein, a chiral Brønsted acid (CBA) catalysis strategy was developed for readily scalable dynamic kinetic resolution of challenging ortho-formyl naphthamides with pyrrolylanilines. The chiral axis of the atropisomeric amide and a stereogenic center were simultaneously established for a new family of potential biologically active pyrrolopyrazine compounds with high enantio- and diastereoselectivities (up to >20 : 1 d.

Controlled chemoselective defluorination and non-defluorination for [5 + 1] aromatic annulation Meisenheimer-type nitrogen anion and radical intermediates.

Reported is a unique chemoselectivity approach to base-promoted defluorinative and Cu(i)-catalyzed aerobic oxidative non-defluorinative [5 + 1] condensation aromatizations of simple unsaturated ketones with ammonium salts Meisenheimer-type nitrogen anion and radical intermediates. The CuBr/O catalysis provides a straightforward approach to diverse 3-fluoropyridines in high yields. The synthetic utility of the strategy is highlighted by the concise synthesis of several F-modified bioactive compounds.

Catalytic Asymmetric Cascade Cyclization for Constructing Three Contiguous Stereocenters in Pyrrolobenzodiazepine-Based Cyclopentanones.

A chiral Brønsted acid catalyzed highly enantio- and diastereoselective cascade cyclization has been developed to streamline the synthesis of valuable multifunctionalized enantioenriched cyclopenta[ f]pyrrolo[1,2- d][1,4]diazepinones bearing three contiguous stereocenters in high yields with excellent control of stereochemistry from a wide range of both readily available 2-furylcarbinols and (1 H-pyrrol-1-yl)anilines, which represents the first asymmetric intramolecular conjugate addition of α,β-unsaturated cycloketones with inert N-substituted pyrroles as well as the first enantioselective aza-piancatelli rearrangement/Friedel-Crafts alkylation cascade reaction.

Brønsted acid-catalyzed aromatic annulation of alkoxyallenes with naphthols: a reaction sequence to larger π-conjugated naphthopyrans with aggregation-induced emission characters.

A practical and readily scalable reaction sequence was developed for the straightforward synthesis of a new family of larger π-conjugated naphthopyrans by a Brønsted acid-catalyzed aromatic annulation of alkoxyallenes with inert naphthols. The cascade pathway involves allylation/cyclization/debenzyloxylation/isomerization/dehydration. The new class of solid state diphenylmethylene substituted naphthopyrans are fluorescent emissive and proved to have aggregation-induced emission (AIE) behavior.

Brønsted Acid-Promoted Friedel-Crafts Alkylation/Cyclization of (7-Hydroxynaphthalenyl)pyrrole or (2-Hydroxyphenyl)pyrroles with Isatins for the Construction of Pyrrolospirooxindole Derivatives.

An efficient trifluoroacetic acid-catalyzed cascade Friedel-Crafts alkylation/cyclization of 1-(7-hydroxynaphthalenyl)pyrrole or 1-(2-hydroxyphenyl)pyrroles with isatins has been developed, providing practical access to a variety of biologically important pyrrole-containing spirooxindoles.

Rh(iii)-Catalyzed regioselective mono- and di-iodination of azobenzenes using alkyl iodide.

A new approach for highly regioselective iodination of azobenzenes with alkyl iodide as the iodinating reagent enabled by Rh-catalyzed oxidative C-H activation has been developed. By changing the oxidant, various mono- and di-iodinated azobenzenes were smoothly obtained in moderate to excellent yields, respectively. The preliminary mechanistic study reveals that the reaction process might undergo electrophilic substitution of the directed ortho metalated five-membered rhodacycle compound by an iodine cationic species generated in situ from alkyl iodide and oxidant.

Tunable Aerobic Oxidative Hydroxylation/Dehydrogenative Homocoupling of Pyrazol-5-ones under Transition-Metal-Free Conditions.

A practical and tunable transition-metal-free aerobic oxidation of pyrazol-5-ones preparing either 4-hydroxypyrazoles (via C-H hydroxylation) or bispyrazoles (via dehydrogenative homocoupling) is described. The KCO/dioxane reagent system predominately promoted hydroxylation to deliver the α-hydroxylated pyrazoles. In contrast, the formation of bispyrazoles was overwhelmingly preferred with CHCN as the reaction medium without any additives.

Assembly of Diversely Substituted Quinolines via Aerobic Oxidative Aromatization from Simple Alcohols and Anilines.

An aerobic oxidative aromatization of simple aliphatic alcohols and anilines under the Pd(OAc)/2,4,6-Collidine/Brønsted acid catalytic system has been established, providing a direct approach for the preparation of diverse substituted quinoline derivatives in high yields with wide functional group tolerance. Practically, the protocol can be easily scaled up to gram-scale and was utilized in the concise formal synthesis of a promising herbicide candidate.

A Green Aerobic Oxidative Synthesis of Pyrrolo[1,2-a]quinoxalines from Simple Alcohols without Metals and Additives.

A practical and concise protocol for the efficient preparation of pyrrolo[1,2-a]quinoxalines through a cascade of alcohol oxidation/imine formation/intramolecular cyclization/oxidative dehydrogenation has been established. A series of substituted pyrrolo[1,2-a]quinoxaline derivatives were constructed readily in yields of 53-93% from the cheap primary alcohols by using dioxygen as the terminal oxidant. Remarkably, the fact that no extra metals and additives were necessary makes this unprecedented aerobic oxidation process highly step- and atom-economical.

From Palladium to Brønsted Acid Catalysis: Highly Enantioselective Regiodivergent Addition of Alkoxyallenes to Pyrazolones.

A highly enantioselective regiodivergent addition of alkoxyallenes to pyrazolones was developed to afford multiply functionalized alkylated products bearing a quaternary carbon stereocenter in high yields with excellent stereoselectivities. One approach is enabled by palladium catalysis, thus leading to branched allylic pyrazol-5-ones under mild reaction conditions. The other is catalyzed by a chiral Brønsted acid to give linear products exclusively.

AgNO3 as nitrogen source for rhodium(iii)-catalyzed synthesis of 2-aryl-2H-benzotriazoles from azobenzenes.

A new approach has been established for Rh(iii)-catalyzed direct aza oxidative cyclization of non-prefunctionalized azobenzenes to provide 2-aryl-2H-benzotriazoles in good yields, in which AgNO3 instead of conventional azide reagents for the first time functions as the nitrogen source for the nitrogenation reaction. Preliminary mechanistic studies suggest that the Rh(iii)-catalyst could account for the nitration reaction, and subsequently cationic silver species might both play a vital role in the fission of the nitrogen-oxygen bonds in nitro groups and promote aza oxidative cyclization.

Palladium-catalyzed highly atom-economical allylation of oxindoles with vinyl cyclopropanes.

A highly atom-economical allylation of oxindoles with vinyl cyclopropanes catalyzed by Pd(PPh3)4 has been developed, setting up a practical venue for the installation of an all-carbon quaternary center at the 3-position in oxindoles under mild reaction conditions. Importantly, the reaction proceeded well without any additives and no waste was produced, affording linear products with high regioselectivities (>20 : 1). Enantioselective allylic alkylation has also been realized to provide the desired products in good yields and 35% ee.

Triarylphosphines as Aryl Donors for Pd(II)-Catalyzed Aromatic Coupling of Oxabenzonorbornadienes.

A new approach was developed for Pd(II)-catalyzed aromatic coupling of oxabenzonorbornadienes with triarylphosphines as both ligands and aryl donors. Diverse functional groups including halo- (F-, Cl-, and Br-), CF3(-), and furyl groups are well tolerated. For unsymmetrical triarylphosphines, the migration ability of aryls is consistent with the electronic property of substituents and maintains the order EDG-Ar > H-Ar > EWD-Ar (EDG means electron-donating group, EWG means electron-withdrawing group).

Metal-free synthesis of ortho-CHO diaryl ethers by a three-component sequential coupling.

A practical, metal-free, and highly chemoselective approach was developed for the synthesis of ortho-CHO diaryl ethers by a three-component sequential coupling of arynes, N,N-dimethylformamide (DMF), and diaryliodonium salts. Diverse functional groups including halo, nitryl, and bulky substituents and heteroaromatics are well tolerated. Mechanistically, isotopic tracer experiments reveal that the diaryliodonium salt serves as an electrophile to trap the transient intermediates generated from the [2 + 2] cyclization of an aryne and DMF.

Brønsted acid accelerated Pd-catalyzed direct asymmetric allylic alkylation of azlactones with simple allylic alcohols: a practical access to quaternary allylic amino acid derivatives.

A Brønsted acid accelerated Pd-catalyzed asymmetric allylic alkylation of azlactones with simple allylic alcohols under mild reaction conditions has been realized, which provides a direct and readily scalable approach for the synthesis of all-carbon quaternary allylic amino acid derivatives in excellent yields and good enantioselectivities.

Enantioselective hydrovinylation via asymmetric counteranion-directed ruthenium catalysis.

The first Ru-catalyzed enantioselective hydrovinylation has been realized by using an asymmetric counteranion-directed catalysis strategy. Styrene derivatives react with ethylene in excellent yields and promising enantioselectivity using this approach.

Highly efficient oxidation of amines to imines by singlet oxygen and its application in Ugi-type reactions.

A variety of secondary benzylic amines were oxidized to imines in 90% to >99% yields by singlet oxygen generated from oxygen and a porphyrin photosensitizer. On the basis of these reactions, a protocol was developed for oxidative Ugi-type reactions with singlet oxygen as the oxidant. This protocol has been used to synthesize C1- and N-functionalized benzylic amines in up to 96% yields.