Liu-Zhu Gong

Cooperative Catalysis with Chiral Brønsted Acid-Rh2(OAc)4: Highly Enantioselective Three-Component Reactions of Diazo Compounds with Alcohols and Imines

An asymmetric three-component reaction of diazo compounds and alcohols with imines catalyzed cooperatively by a rhodium complex and a chiral Brønsted acid provides a general and efficient entry to beta-amino-alpha-hydroxyl acid derivatives in high yields with excellent stereoselectivities.

Asymmetric Organocatalytic Three-Component 1,3-Dipolar Cycloaddition: Control of Stereochemistry via a Chiral Brønsted Acid Activated Dipole

A Brønsted acid catalyzed three-component asymmetric 1,3-dipolar addition reaction between aldehydes, amino esters, and dipolarophiles by a new bisphosphoric acid, derived from the linked BINOL, furnished multiply substituted pyrrolidines in high yield with excellent enantioselectivities under mild conditions.

Novel Achiral Biphenol‐Derived Diastereomeric Oxovanadium(IV) Complexes for Highly Enantioselective Oxidative Coupling of 2‐Naphthols

Optically pure 1,1’-binaphthol and its derivatives have been evaluated as versatile chiral auxiliaries and ligands in asymmetric transformations. Research in this area has provided many efficient and useful methods for the preparation of key chiral building blocks, some of which have been used for the construction of complex natural products.[1] They have also been extensively applied to the preparation of chiral organic materials.[2] The wide-ranging and important applications of such compounds in organic synthesis have stimulated great interest in developing efficient methods for their preparation.[3] Compared to the well-established resolution of racemic binaphthol for the preparation of optically pure BINOL,[3a±f] catalytic asymmetric preparation of chiral binaphthols has developed much more slowly. The discovery of efficient catalysts for the highly enantioselective formation of optically active binaphthol and its derivatives is an attractive target. The oxidative coupling of 2-naphthols in the presence of a catalytic amount of a copper complex of a chiral amine has provided several promising results, but high enantioselectivity has been achieved only for the coupling of 3carboalkoxyl-2-naphthols (93% ee).[4] A photo-activated chiral [RuII(salen)(NO)] complex catalyzes the aerobic oxidative coupling of 2-naphthols with 33±71% ee.[5] Chen et al. and Uang et al. independently designed similar oxovanadium(iv) complexes of chiral Schiff bases for the asymmetric oxidative coupling of 2-naphthols with moderate enantioselectivities of up to 62% ee.[6] We developed the catalyst (R,S)-1c for the oxidative coupling of 2-naphthol with high enantioselectivity, and found that the chiral centers on the amino acid part and the axially chiral binaphthyl unit are both crucial to stereocontrol by the catalyst.[7] However, a drawback is that the chiral oxovanadium complex must be prepared from an optically pure 3,3’diformyl-2,2’-dihydroxy-1,1’-binaphthol and (S)-amino acid. The catalyst is only highly enantioselective when the two COMMUNICATIONS

Palladium-catalyzed allylic alkylation of tert-butyl(diphenylmethylene)-glycinate with simple allyl esters under chiral phase transfer conditions

Abstract The first example of palladium-catalyzed allylic alkylation of an imino ester with simple allyl esters in the presence of a chiral quaternary ammonium salt is reported. The presence of molecular sieves was found to have a beneficial effect on the enantioselectivity of the reaction by scavenging water from the system. Alkylated products with e.e.s of up to 61% were obtained.

Salen-Ti(OR)4 complex catalysed trimethylsilylcyanation of aldehydes

Abstract Chiral salen-titanium complexes were found to be efficient catalysts for the enantioselective trimethylsilylcyanation of aldehydes. An enantioselectivity up to 87.1% e.e. was obtained by using 10mol% Ti(IV)-salen 2d as catalyst. The reaction mechanism was proposed and proved experimentally.

The role of double hydrogen bonds in asymmetric direct aldol reactions catalyzed by amino amide derivatives

The double hydrogen bonding activation of carbonyl functionality has been a general strategy for the design of amino amide organocatalysts for highly enantioselective direct aldol reactions of various ketones with aldehydes conducted in either organic solvents or aqueous media. Moreover, this concept may suggest an activation mode to create new catalysts for other related asymmetric transformations.

REDUCTION OF AZIDES TO AMINES OR AMIDES WITH ZINC AND AMMONIUM CHLORIDE AS REDUCING AGENT

ABSTRACT Alkyl azides and acyl azides were reduced to the corresponding amines and amides with zinc and ammonium chloride as reducing agent under mild conditions in good to excellent yield.

L-Prolinamide-catalyzed direct nitroso aldol reactions of α-branched aldehydes: a distinct regioselectivity from that with L-proline

The first direct enantioselective N-nitroso aldol reaction of aldehyde with nitrosobenzene catalyzed by an L-prolinamide derivative is presented; the reactions proceed smoothly furnishing the -hydroxyamino carbonyl compounds, the otherwise disfavored products, in good yields with up to 64% ee.

Asymmetric Synthesis of 3-Amino-δ-lactams and Benzo[a]quinolizidines by Catalytic Cyclization Reactions Involving Azlactones

d-lactams into peptides led to a family of conformationally constrained surrogates that showed enhanced biological activities in comparison with their parent molecules. 3-Aminopiperidine, which can be obtained from the reduction of 3-amino-d-lactams, has served as a core structural element commonly appearing in biologically active molecules. For example, alogliptin can be used for the treatment of diabetes, and CP-690550 serves as a Janus kinase 3 (JAK3) inhibitor, an immunosuppressive agent exhibiting potent effects in preclinical transplantation and arthritis models. Currently, the synthesis of such structural motifs has been restricted to chiral auxiliary-induced asymmetric synthesis and to chiral resolution. Catalytic enantioselective methods to access these compounds would be highly valuable in both pharmaceutical and organic chemistry, but remain unknown. Azlactones possessing three reactive sites at C-2, C-4, and C-5, of which both C-2 and C-5 are electrophilic, while C-4 is nucleophilic, have been versatile reactants for the development of synthetically important reactions. For instance, these azlactones could undergo cycloaddition at C-4 and C-5 with 1,3-azabutadienes, directly providing racemic 3,4-dihydropyridinones. However, no enantioselective versions of this reaction have yet been disclosed. In view of the synthetic significance of chiral 3,4-dihydropyridinones and the unavailibility of enantioselective methods to access them, we became interested in the asymmetric cycloaddition of azlactones with 1,3-azabutadienes. Herein, we report the first asymmetric catalytic three-component cyclization reaction of cinnamaldehydes, primary amines, and azlactones by using chiral Brønsted acid catalysts, which yields dihydropyridinones with high enantioselectivity. The use of this reaction in the facile synthesis of benzo[a]quinolizidine derivatives with high optical purity is also described. Inspired by elegant findings of Brønsted acid catalysis, we have established a cyclization reaction of 1,3-dicarbonyls with 1,3-azadiene catalyzed by phosphoric acids. The phosphoric acid was considered to protonate 1,3-azadiene, generating an active iminium species and thereby lowering the LUMO of 1,3-azadiene, as indicated in asymmetric counteranion directed catalysis. Additionally, the Brønsted acid is also presumably able to activate the azlactone through a hydrogen bond. This presumed dual activation strategy (Scheme 1, I) prompted us to consider that chiral phosphoric acids might be able to control the stereochemistry of the cycloaddition of 1,3-azabutadienes with azlactones [a] J. Qing, Prof. L.-Z. Gong Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry University of Science and Technology of China Hefei, 230026 (China) Fax: (+86) 551-3606266 E-mail : gonglz@ustc.edu.cn [b] J. Jiang Chengdu Institute of Organic Chemistry Chinese Academy of Sciences (CAS) Chengdu, 610041 (China) [c] J. Jiang Graduate School of Chinese Academy of Sciences, Beijing (China) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200900814.

Direct Assembly of Aldehydes, Amino Esters, and Anilines into Chiral Imidazolidines via Brønsted Acid Catalyzed Asymmetric 1,3-Dipolar Cycloadditions

A chiral Brønsted acid catalyzed 1,3-dipolar cycloaddition reaction directly assembles aldehydes, amino esters, and anilines into synthetically useful chiral imidazolidines with high levels of stereoselectivity (up to 91/9 dr and 98% ee).