Junmin Zhang

Enantioselective Oxidative Cross-Dehydrogenative Coupling of Tertiary Amines to Aldehydes**

The direct oxidative cross-dehydrogenative coupling (CDC) of two C H bonds can be an efficient and relatively clean strategy in organic synthesis. Various sp C Hbonds, such as benzylic and allylic C H bonds, the a-C H bonds of amines and ethers, and the C H bonds of alkanes can be oxidized for direct reaction with carbon nucleophiles. Among these reactions, the oxidation of tertiary amines to generate iminium intermediates, as pioneered by Murahashi et al., Li et al. and others, has received considerable attention. Carbonyl compounds, such as 1,3-dicarbonyls, 10b,g] a,bunsaturated ketones, and simple ketones have been successfully coupled with tertiary amines by using metal catalysis, acid catalysis, metal/organic cooperative catalysis, or photoredox catalysis. In all of these reactions, the development of enantioselective catalysis remains a challenge. Very recently, Wang and co-workers used metals together with chiral bisoxazoline ligands to realize enantioselective reactions of activated carbonyl nucleophiles (such as 1,3dicarbonyls and acetyl phosphates) to oxidatively generate iminiums or their analogues. However, this approach with chiral ligands was found to be unsuccessful for reactions starting with simple ketone nucleophiles, as reported by Klussmann and co-workers as well as Xie and Huang. Approaches that use asymmetric enamine catalysis for the activation of carbonyl compounds have led to disappointing results (for example, less than 20% ee) as well . As part of a larger program for developing sustainable oxidation chemistry, we herein report an enantioselective oxidative coupling reaction of aldehydes and tertiary amines under cooperative amine and metal catalysis. The racemic version of this reaction was also realized by using metal catalysts alone (without amine catalysts), on account of its potential utility and the very different optimized conditions, relative to the enantioselective reactions. We examined metal-catalyzed oxidative coupling reactions between N-phenyltetrahydroisoquinoline (1a) and propionaldehyde (2a) in the presence of tBuOOH without an amine catalyst. An initial survey of solvents and catalysts indicated that DMF is a good solvent and CuBr2 is an effective metal catalyst (Table 1, entries 1–3, see also the Supporting Information). The amino aldehyde product 3a is unstable and, thus, was isolated as the corresponding amino alcohol product 4a in 72% yield after reduction with NaBH4 in situ, albeit with no diastereoselectivity (Table 1, entry 3). Under these conditions, various amines, such as N-aryl tetrahydroisoquinolines 1 and N,N-dialkyl anilines, and aldehydes 2 were used to obtain the corresponding racemic amino alcohols 4 in acceptable yields. Aldehydes with longer carbon chains required elevated reaction temperatures. N,Ndialkyl anilines gave the corresponding products in lower yields (Table S6 and Scheme S3 in the Supporting Information).

Asymmetric Organocatalytic Double-Conjugate Addition of Malononitrile to Dienones: Efficient Synthesis of Optically Active Cyclohexanones

9-Amino-9-deoxyepiquinine efficiently catalyzed the double-conjugate addition of malononitrile to dienones. A number of 1,1,2,6-tetrasubstituted cyclohexanones were prepared in good yields, diastereoselectivities, and excellent enantioselectivities.

Catalytic Activation of Carbohydrates as Formaldehyde Equivalents for Stetter Reaction with Enones

We disclose the first catalytic activation of carbohydrates as formaldehyde equivalents to generate acyl anions as one-carbon nucleophilic units for a Stetter reaction. The activation involves N-heterocyclic carbene (NHC)-catalyzed C-C bond cleavage of carbohydrates via a retro-benzoin-type process to generate the acyl anion intermediates. This Stetter reaction constitutes the first success in generating formal formaldehyde-derived acyl anions as one-carbon nucleophiles for non-self-benzoin processes. The renewable nature of carbohydrates, accessible from biomass, further highlights the practical potential of this fundamentally interesting catalytic activation.

Facile Access to Chiral Ketones through Metal‐Free Oxidative CC Bond Cleavage of Aldehydes by O2

Functionalized chiral ketones, such as a-amino ketones, bnitro ketones, and their derivatives, are prevalent building blocks and ubiquitous subunits present in natural products and pharmaceutical lead compunds. The synthesis of chiral ketones can be achieved through direct a substitution. For example, the synthesis of a-amino ketones has been developed by Jørgensen and co-workers using an elegant catalytic amination of ketones by diethyl diazenedicarboxylate (DEAD). Despite the success, some drawbacks of this method lie in the unsatisfactory and undesired regioselectivities for unsymmetric ketones, and to a certain extent the demanding reaction conditions required for subsequent N N bond cleavage. Another approach for chiral ketone synthesis employs N-heterocyclic carbene catalysis. Rovis and coworkers have recently reported excellent asymmetric Stetter reactions of aldehydes to nitroalkenes to afford b-nitro ketones. The aldehyde substrates are restricted to (hetero)aryl aldehydes and enals as the acyl anion precursors, and usually only aliphatic nitroalkenes can behave as effective Michael acceptors. We envisioned that limitations associated with current new bond-forming reactions for chiral ketone synthesis could be substantially overcome by a less common C C bond-breaking approach (Scheme 1).

Brønsted Acid Catalyzed α‐Alkylation of Aldehydes with Diaryl Methyl Alcohols

The catalytic a-alkylation of carbonyl compounds is a common approach in organic synthesis. In recent years, many efforts have been directed towards the activation of ketones and aldehydes by means of enamine catalysis to react with a broad range of electrophiles. In 2004, List reported an elegant intramolecular alkylation of aldehydes with alkyl halides using proline-based amine catalysts. While the long-sought intermolecular versions of such enamine-catalytic SN2-type a-alkylation of aldehydes [3] remain challenging, research by the groups of Melchiorre, Cozzi, Jacobsen and others have pioneered the amine-mediated SN1type intermolecular reactions between aldehydes and arylsulfonyl indoles, diaryl alcohols, or halides. In the approach used by Cozzi and others, amine catalysts were used to activate the aldehydes via enamine intermediates, and Bronsted acids were used to mediate the formation of diaryl methyl cations from the corresponding diaryl methanols. Despite the success of this amine/acid co-catalysis approach for diaryl methyl alcohols (e.g., 1a) that generate highly stabilized carbocations, the scope of the reactions still remains limited: diaryl methyl alcohols (such as 1b–f) that lead to “less stabilized” diaryl methyl carbocation electrophiles are ineffective substrates in these alkylation reactions. Instead of using enamine catalysis for aldehyde activation, here we disclose the use of Bronsted acids alone to catalyze these SN1 type aldehyde alkylations. The acid catalyst is believed to facilitate the formation of alcohol-derived carbocations and to accelerate the enolization of aldehydes. A much broader scope of substrates is thereby realized: diaryl methyl alcohols that lead to less stabilized carbocations can be used; aldehydes with a,a-disubstituents react efficiently as well to generate products containing quaternary carbon centers. Our work began by using diaryl methanol 1b as a model substrate to develop an acid-catalysis approach. According to the Mayr reactivity scales, such substrates lead to lessstabilized carbocations (e.g., compared to that from 1a) and were ineffective using the enamine/acid co-catalytic strategies. The results of our initial studies are summarized in Table 1. Weak acids, such as acetic acid, could not mediate

Toxicity, degradation and metabolic fate of ibuprofen on freshwater diatom Navicula sp.

Ibuprofen (IBU) is one of the most widely used and frequently detected human pharmaceuticals in aquatic environment. However, the toxicity of IBU on diatom and its fate remain still unkown. In the present study, the toxicity of IBU on the diatom was evaluated by the algal growth rate, the chlorophyll-a and carotenoids contents. The degradation of IBU including in particular the potential for the formation of incomplete degradation products was also explored. Biochemical characteristics of Navicula sp. were significantly inhibited at IBU concentrations up to 50mgL-1 after 10days of exposure. The degradation of IBU was retarded by Navicula sp. at low concentration (1mgL-1), with t1/2 being extended from 9.6±1.8 d to 12.0±1.5 d, indicating that Navicula sp. could prolong the exposure time of IBU. A total of 8 metabolites were identified by LC-MS/MS and the degradation pathway of IBU in Navicula sp. was proposed. Hydroxylation, acylation, demethylation, and glucuronidation contributed to IBU transformative reactions in diatom cells. These findings indicate that the presence of diatom Navicula sp. could hinder degradation of IBU, and IBU and/or its metabolites may pose high risks on aquatic ecosystem in natural waters.

Scalable 2D Hierarchical Porous Carbon Nanosheets for Flexible Supercapacitors with Ultrahigh Energy Density

2D carbon nanomaterials such as graphene and its derivatives, have gained tremendous research interests in energy storage because of their high capacitance and chemical stability. However, scalable synthesis of ultrathin carbon nanosheets with well-defined pore architectures remains a great challenge. Herein, the first synthesis of 2D hierarchical porous carbon nanosheets (2D-HPCs) with rich nitrogen dopants is reported, which is prepared with high scalability through a rapid polymerization of a nitrogen-containing thermoset and a subsequent one-step pyrolysis and activation into 2D porous nanosheets. 2D-HPCs, which are typically 1.5 nm thick and 1-3 µm wide, show a high surface area (2406 m2 g-1 ) and with hierarchical micro-, meso-, and macropores. This 2D and hierarchical porous structure leads to robust flexibility and good energy-storage capability, being 139 Wh kg-1 for a symmetric supercapacitor. Flexible supercapacitor devices fabricated by these 2D-HPCs also present an ultrahigh volumetric energy density of 8.4 mWh cm-3 at a power density of 24.9 mW cm-3 , which is retained at 80% even when the power density is increased by 20-fold. The devices show very high electrochemical life (96% retention after 10000 charge/discharge cycles) and excellent mechanical flexibility.

Hydrophilic Sponges for Leaf-Inspired Continuous Pumping of Liquids

A bio‐inspired, leaf‐like pumping strategy by mimicking the transpiration process through leaves is developed for autonomous and continuous liquid transport enabled by durable hydrophilic sponges. Without any external power sources, flows are continuously generated ascribed to the combination of capillary wicking and evaporation of water. To validate this method, durable hydrophilic polydimethylsiloxane sponges modified with polyvinyl alcohol via a “dip‐coat‐dry” method have been fabricated, which maintains hydrophilicity more than 2 months. The as‐made sponges are further applied to achieve stable laminar flow patterns, chemical gradients, and “stop‐flow” manipulation of the flow in microfluidic devices. More importantly, the ease‐of‐operation and excellent pumping capacity have also been verified with over 24 hs pumping and quasi‐stable high flow rates up to 15 µL min−1. The present strategy can be easily integrated to other miniaturized systems requiring pressure‐driven flow and should have potential applications, such as cell culture, micromixing, and continuous flow reaction.

Microfluidic Patterning of Metal Structures for Flexible Conductors by In Situ Polymer‐Assisted Electroless Deposition

A low‐cost, solution‐processed, versatile, microfluidic approach is developed for patterning structures of highly conductive metals (e.g., copper, silver, and nickel) on chemically modified flexible polyethylene terephthalate thin films by in situ polymer‐assisted electroless metal deposition. This method has significantly lowered the consumption of catalyst as well as the metal plating solution.

Bismuth(III) chloride-promoted efficient synthesis of perimidine derivatives under ambient conditions

Abstract Various biologically important perimidine derivatives have been efficiently synthesized in excellent yields from naphthalene‐1,8‐diamine and various ketones in the presence of a catalytic amount of BiCl3.