Chunyin Zhu

A Concise Synthesis of (+)-Artemisinin

Malaria represents one of the most medically and economically debilitating diseases present in the world today. Fortunately, there exists a highly effective treatment based on the natural product artemisinin. Despite the development of several synthetic approaches to the natural product, a streamlined synthesis that utilizes low-cost chemical inputs has yet to materialize. Here we report an efficient, cost-effective approach to artemisinin. Key to the success of the strategy was the development of mild, complexity-building reaction cascades that allowed the use of readily available, affordable cyclohexenone as the key starting material.

Tandem Michael addition/ylide epoxidation for the synthesis of highly functionalized cyclohexadiene epoxide derivatives

A highly efficient diastereoselective synthesis of cyclohexadiene epoxide derivatives with a multi-stereocenter has been developed via a tandem ylide Michael addition/epoxidation. By employing a chiral sulfonium ylide, up to 96% ee can be achieved in good yields.

Highly diastereoselective and enantioselective formal [4 + 1] ylide annulation for the synthesis of optically active dihydrofurans.

On the basis of the reactions of camphor-derived sulfur ylide with alpha-ylidene-beta-diketones, highly efficient and selective synthesis of optically active dihydrofurans has been achieved.

Highly enantioselective synthesis of isoxazoline N-oxides

The reaction of cinchonidine (cinchonine)-derived ammonium salts with nitroolefins in the presence of Cs2CO3 to afford optically active isoxazoline N-oxides with excellent ee and high de values has been developed.

Wacker-Type Oxidation of Internal Alkenes using Pd(Quinox) and TBHP

The Pd-catalyzed TBHP-mediated Wacker-type oxidation of internal alkenes is reported. The reaction uses 2-(4,5-dihydro-2-oxazolyl)quinoline (Quinox) as ligand and TBHP(aq) as oxidant to deliver single ketone constitutional isomer products in a predictable fashion from electronically biased olefins. This methodology is showcased through its application on an advanced intermediate in the total synthesis of the antimalarial drug artemisinin.

Reaction of Allylic Phosphoranes with Iron Porphyrin Carbenoids: Efficient, Selective, and Catalytic Intermolecular Formal Carbenoid Insertion into Olefinic C−H Bonds

A highly efficient, selective, and catalytic intermolecular formal carbenoid insertion reaction into olefinic C-H bonds of allylic phosphoranes is described. This novel insertion reaction proved to proceed via a catalytic cyclopropanation of allylic phosphoranes with diazoacetate, followed by ring opening of the resulting cyclopropane ylide. On the basis of this observation, a facile synthetic method yielding 1,1,4-trisubstituted 1,3-butadienes with high stereoselectivity by a one-pot reaction of tributylphosphine-derived salt 11 with MDA and aldehydes under mild conditions has been developed.

Visible-Light Photocatalytic Aerobic Annulation for the Green Synthesis of Pyrazoles

A selective and high yielding synthesis of polysubstituted pyrazoles through a VLPC (visible light photoredox catalysis)-promoted reaction of hydrazine with Michael acceptors is reported. The method employs very mild reaction conditions and uses air as the terminal oxidant, which makes the process environmentally benign. Different types of Michael acceptors with various substituents can undergo the reaction to afford corresponding pyrazoles in good to excellent yields. The reaction is proposed to go through VLPC-promoted oxidation of hydrazine to diazene followed by its addition to Michael acceptors, other than the conventional condensation of hydrazine with a carbonyl.

Application of Asymmetric Ylide Cyclopropanation in the Total Synthesis of Halicholactone

Halicholactone belongs to a family of oxylipins that have important and interesting biological activities, such as inhibiting lipoxygenase and farnesyl protein transferase. These compounds are featured unique molecular structures containing a 1,2-trans-substituted cyclopropane subunit with a 6-, 8or 9-membered lactone (Figure 1). The first total synthesis of halicholactone 1 was accomplished by Wills et al. using (S)-malic acid as the starting material. In their synthesis, the cyclopropane fragment was obtained by the reaction of the unsaturated ester with Corey ylide; the lactone unit was constructed by Yamaguchi s mixed anhydride method. Later, Takemoto, Tanaka, and their co-workers reported an asymmetric total synthesis of halicholactone 1 from chiral [(diene)Fe(CO)3], in which the cyclopropane fragment was prepared in moderate yields with excellent diastereoselectivity by the modified Simmons–Smith reaction of a chiral allylic alcohol. Kitahara documented a total synthesis of halicholactone by using (1S,5S,6R)-5hydroxybicycloACHTUNGTRENNUNG[4.1.0]-heptan-2-one as a chiral building block. Datta s group described a 12-step synthesis of compound 29 by employing the cyclopropanation of trans-cinnamyl alcohol through Charette s protocol, finishing the formal synthesis of halicholactone. Mohapatra et al. also reported the total synthesis of halicholactone with (R)-2,3-Oisopropylidene glyceraldehyde as a chiral pool building block. In our studies on ylide chemistry in organic synthesis, we developed an efficient method for the preparation of vinylcyclopropanes from a readily available d-camphorderived ylide. In this cyclopropanation, excellent diastereoselectivity (cis/trans) and enantioselectivity can be achieved. Very recently, we found that this cyclopropanation could be applied successfully to the preparation of intermediate 13 in five steps to provide a formal synthesis of halicholactone. In this communication, we wish to report our results as well as the total synthesis of halicholactone in detail.

Efficient one-pot production of 1,2-propanediol and ethylene glycol from microalgae (Chlorococcum sp.) in water

The catalytic valorization of microalgae, a sustainable feedstock to alleviate dependence on fossil fuel and offset greenhouse gases emissions, is of great significance for production of biofuels and value-added chemicals from aquatic plants. Here, an interesting catalytic process is reported to convert microalgae (Chlorococcum sp.) into 1,2-propanediol (1,2-PDO) and ethylene glycol (EG) in water over nickel-based catalysts. The influences of reaction temperature, initial H2 pressure and reaction time on the product distribution were systematically investigated by using a batch reactor. Under optimal reaction conditions (at 250 °C for 3 h with 6.0 MPa of H2 pressure), microalgae were directly and efficiently converted over a Ni–MgO–ZnO catalyst and the total yield of polyols was up to 41.5%. The excellent catalytic activity was attributed to the smaller size and better dispersion of Ni particles on the MgO–ZnO supporter based on the characterization results as well as its tolerance to nitrogen-containing compounds. Besides, the reaction pathway was proposed based on the formation of reaction intermediates and the results of model compound conversion.

Metal-free synthesis of ketones by visible-light induced aerobic oxidative radical addition of aryl hydrazines to alkenes

A green and cost-effective method has been developed for the conversion of alkenes to ketones under metal-free conditions. The reaction involves the oxidative addition of alkenes with aryl radicals, which are generated by visible-light induced aerobic oxidation of arylhydrazines. The key features of this reaction include broad substrate scope, readily available reagents and amenability to gram-scale synthesis.