Yuanyong Yang

Graphene oxide and Rose Bengal: oxidative C–H functionalisation of tertiary amines using visible light

Visible light induced oxidative C–H functionalisation of tertiary amines catalysed by the combination of graphene oxide and Rose Bengal was developed. This reaction avoids the use of stoichiometric amounts of peroxy compounds as terminal oxidants. This reaction is useful for tri-alkyl amines including chiral tertiary amines. Both cyanide and trifluoromethyl nucleophiles were shown to participate in this reaction, providing α-cyano- and α-trifluoromethylated tertiary amines.

Synthesis of a Chiral Quaternary Carbon Center Bearing a Fluorine Atom: Enantio‐ and Diastereoselective Guanidine‐Catalyzed Addition of Fluorocarbon Nucleophiles

The perfect combination: The title reaction provides adducts having quaternary carbon centers bearing a fluorine atom with high ee and d.r. values (see scheme). The mechanism and origin of stereoselectivity were elucidated by DFT calculations. The bifunctional mode of the guanidine catalysis was demonstrated in the transition states resulting from the DFT results.

Expanding the Utility of Brønsted Base Catalysis: Biomimetic Enantioselective Decarboxylative Reactions

As a result of the low reactivity of simple esters, the use of them as nucleophiles in direct asymmetric transformations is a long-standing challenge in synthetic organic chemistry. Nature approaches this difficulty through a decarboxylative mechanism, which is used for polyketide synthesis. Inspired by nature, we report guanidine-catalyzed biomimetic decarboxylative C-C and C-N bond-formation reactions. These highly enantioselective decarboxylative Mannich and amination reactions utilized malonic acid half thioesters as simple ester surrogates. It is proposed that nucleophilic addition precedes decarboxylation in the mechanism, which has been investigated in detail through the identification of intermediates by using electrospray ionization (ESI) mass-spectrometric analysis and DFT calculations.

Fluorinated Aromatic Ketones as Nucleophiles in the Asymmetric Organocatalytic Formation of CC and CN Bonds: A Facile Route to the Construction of Fluorinated Quaternary Stereogenic Centers.

The development of a broadly useful platform for the organocatalytic nucleophilic addition of carbonyl compounds represents a major research field in asymmetric catalysis. Recent research efforts have mainly focused on dicarbonyl compounds such as b-ketoesters and b-ketosulfones, which are easily activated and widely used in many conjugated addition reactions. Most of the aliphatic ketones and acetophenone nucleophiles used in organocatalytic asymmetric transformations rely on the formation of highly reactive enamine intermediates. On the other hand, Brønsted bases are seldom used as catalysts in reactions of simple carbonyls because of to the rather low basicity of most organobases, and thus their inability to activate the carbonyl group through enolization. Successful strategies are those that try to increase the acidity of the a-proton. For example, activated esters, such as trifluoroethyl thioesters, acyanothioacetates, a-substituted cyanoacetates, and anitroacetates, are valuable nucleophiles for organic basecatalyzed reactions because of their enhanced acidity. In contrast, fused cyclic aromatic ketones are still challenging substrates to activate as a result of the difficulty in forming the enamine intermediate and their poor reactivity. To our knowledge, the use of activated aromatic ketones as nucleophiles for Brønsted base-catalyzed reactions is restricted to several reports which focused on a-cyano ketones. Organofluorine compounds are important in medicinal and bioorganic chemistry. Enantiopure compounds containing a fluorine atom directly connected to a quaternary carbon center are nontrivial to prepare. The most common approach thus far is to generate such compounds through an enantioselective fluorination of tertiary carbon nucleophiles using chiral transition-metal complexes or organocatalysts. The less explored route is the asymmetric formation of C C bonds by using fluorocarbon nucleophiles. Recently, a-fluoro-b-ketoesters have been employed as fluorocarbon nucleophiles in organocatalytic processes, asymmetric Michael, amination, and Mannich reactions. The asymmetric alkylation of a-fluoro-b-ketoACHTUNGTRENNUNGesters under phase-transfer conditions, and asymmetric Robinson annulations have been carried out using fluorocarbon nucleophiles. Other fluorocarbon nucleophiles such as 1-fluoro-bis(phenylsulfonyl)methane (FBSM) and 1fluoro-1-nitro(phenylsulfonyl)methane (FNSM) were also developed. We have also shown that the a-fluoro-b-ketoACHTUNGTRENNUNGester and the a-fluoro-b-keto ACHTUNGTRENNUNGacyloxazolidinone underwent guanidine-catalyzed enantioselective Michael and Mannich reactions, which resulted in high enantioselectivities. The use of simple a-fluorinated aromatic ketones as nucleophiles has been less studied. However, there were two independent reports on the use of phase-transfer catalysts for asymmetric alkylation reactions of a-fluorotetralone that resulted in unsatisfactory enantioselectivities and yields. Herein, we present the highly enantioselective formation of C N and C C bonds using a-fluorinated aromatic ketones as nucleophiles. Our initial efforts focused on the aamination reaction of a-fluorinated aromatic ketones catalyzed by a bicyclic chiral guanidine. To the best of our knowledge, there are no reports on enantioselective synthesis of nitrogen-substituted fluorinated stereogenic carbons from a-fluorinated ketones using organocatalytic processes. However, successful examples using a-fluoro-b-ketoesters and catalyzed with copper and nickel complexes of Cinchona alkaloid derivatives have been reported. Direct a-amination of a-fluorinated aromatic cyclic ketones 1 d catalyzed by chiral guanidine 2 with azodicarboxylates 3 led to optically active a-hydrozino-a-fluorinated aromatic cyclic ketones 4 and 5 d. When di-tert-butyl azodicarboxylate 3 a was used as the nitrogen source (Table 1, entries 1–7), the best result obtained was 84 % ee in THF (Table 1, entry 7). A bulkier version of azodicarboxylate, di3-ethylpentan-3-yl azodicarboxylate 3 b (EocN=NEoc), was designed as we are aware that bicyclic guanidine catalyst responds positively to an increase in the steric demand of the [a] Y. Zhao, Y. Pan, H. Liu, Y. Yang, Prof. Dr. C.-H. Tan Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) Fax: (+65) 6779-1691 E-mail : chmtanch@nus.edu.sg [b] Prof. Dr. Z. Jiang Provincial Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University Jinming Campus, Kaifeng, Henan, 475004 (P.R. China) Fax: (+86) 0378-2864665 E-mail : chmjzy@henu.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201003761.

Synthesis of α‐Stereogenic Amides and Ketones by Enantioselective Conjugate Addition of 1,4‐Dicarbonyl But‐2‐enes

In the conjugate addition reaction of a alpha,beta-unsaturated compound, the new stereogenic center is created in the beta-position. In contrast, conjugate addition to 1,4-dicarbonyl but-2-enes will generate an alpha-stereogenic center with respect to one of the carbonyl groups, which informally, can be considered as an inversion of normal reactivity patterns or Umpolung. In this paper, we demonstrate that chiral bicyclic guanidine can catalyze the addition of 1,3-dicarbonyl compounds to 1,4-dicarbonyl but-2-enes [(E)-4-oxo-4-arylbutenamides and (E)-4-oxo-4-arylbutenones] with high regioselectivity and enantioselectivity (ee values up to 97%).