Qing-Wei Zhang

Organocatalytic asymmetric halogenation/semipinacol rearrangement: highly efficient synthesis of chiral α-oxa-quaternary β-haloketones.

A novel asymmetric halogenation/semipinacol rearrangement reaction catalyzed by cinchona alkaloid derivatives was developed. Two types of β-haloketones (X = Br, Cl) were obtained with up to 95% yield and 99% enantiomeric excess. The desired (+) and (-) enantiomers of the β-haloketones were readily obtained.

Enantioselective bromination/semipinacol rearrangement for the synthesis of β-bromoketones containing an all-α-carbon quaternary center

A bromination/semipinacol rearrangement reaction catalyzed by cinchona alkaloid derivatives was developed. With 5 mol% (DHQD)2PYDZ, β-bromoketones containing an all-α-carbon quaternary center, which were synthetically useful but challenging to construct, were obtained in up to 97% yield and 93% ee.

Formal Synthesis of (−)‐Cephalotaxine Based on a Tandem Hydroamination/Semipinacol Rearrangement Reaction

( )-Cephalotaxine 1 was first isolated from Cephalotaxus drupacea and C. fortunei as a major alkaloid among a series of its ester derivatives in 1963. Much attention has been paid towards the studies of cephalotaxine due to the unique pentacyclic structure and antileukemic activity of its derivatives. As a classic target for organic chemists, the syntheses of cephalotaxine have been continuing since the pioneering work of Weinreb and Semmelheck in 1972. Among the various strategies reported, the establishment of the 1azaspiroACHTUNGTRENNUNG[4.4]nonane ring system 2 followed by benzazepine formation were most frequently introduced (Figure 1). Thus, an effective construction of this unit would be of great importance in the synthesis of cephalotaxine and other structurally related alkaloids such as serratine and stemonamine. Azaspiro ACHTUNGTRENNUNG[4.4]nonane 2-type azaspirocycles have long been recognized as useful building blocks and recently been selected as templates for pharmaceutical investigations. A number of methods have been developed to construct this structural unit in the context of total synthesis. However, these methods often require multiple manipulations, installing the aza-quaternary carbon center and each of the spiro rings in separate steps. Additionally, chiral syntheses of this unit are mainly based either on chiral auxiliaries or chiral starting materials. As far as we are aware, catalytic asymmetric synthesis of this kind of azaspirocycles has not been reported. In connection with our longstanding works on the semipinacol rearrangement reaction and its application in total synthesis of polycyclic alkaloids, we intended to develop a highly efficient catalytic asymmetric formal synthesis of ( )-1, taking advantage of the tandem hydroamination/semipinacol rearrangement reaction. As shown in Scheme 1, according to the procedure by Isono and Mori, ( )-cephalotaxine 1 could be obtained in four steps from 3, which has generally been introduced as

An Efficient Total Synthesis of (±)-Stemonamine

An efficient first approach to the Stemona alkaloid (+/-)-Stemonamine has been developed on the basis of a key TiCl4 promoted tandem Semipinacol rearrangement/Schmidt reaction and a Dieckmann condensation reaction.

Organocatalytic asymmetric fluorination/semipinacol rearrangement: an efficient approach to chiral β-fluoroketones.

An asymmetric fluorination/semipinacol rearrangement of 2-oxa allylic alcohols, as catalyzed by cinchona-alkaloid derivatives, gives chiral β-fluoro ketones with moderate to high levels of enantioselectivity (see scheme). Both enantiomers of the product could be obtained by using the appropriate catalyst.

Formal syntheses of (+/-)-stemonamine and (+/-)-cephalotaxine.

A short and efficient approach to aza-quaternary pyrrolo[1,2-a]azepine 8 and aza-quaternary indolizine 23, as the crucial intermediates for syntheses of stemonamine (1a) and cephalotaxine (1b), has been developed on the basis of the key intramolecular Schmidt reaction of symmetric azido-diones 5 and 18, respectively.

One-Pot Synthesis of Aminoenone via Direct Reaction of the Chloroalkyl Enone with NaN3: Rapid Access to Polycyclic Alkaloids

A new one-pot procedure for the preparation of aminoenone from chloroalkyl enone and sodium azide was demonstrated. The structure of the presumed triazoline intermediate in this process was confirmed by X-ray analysis for the first time. As the application of this methodology, the synthesis of polycyclic alkaloid hexahydroapoerysopine (1a) was achieved through an efficient synthetic route.

Catalytic intermolecular carbon electrophile induced semipinacol rearrangement

A catalytic intermolecular carbon electrophile induced semipinacol rearrangement was realized and the asymmetric version was also preliminarily accomplished with 92% and 82% ee. The complex tricyclic system architecture with four continuous stereogenic centers could be achieved from simple starting materials in a single step under mild conditions.

Direct Syntheses of Spiro- and Fused-Hydrofurans by a Tunable Tandem Semipinacol Rearrangement/Oxa-Michael Addition Protocol

A highly chemoselective one-pot reaction has been developed involving a tandem semipinacol rearrangement/oxa-Michael addition sequence in which the in situ generated ketol diene intermediate can be transformed specifically to either the spiro- or fused-dihydrofuran products (see scheme). This one-pot tandem reaction represents a general synthetic methodology for the syntheses of the two different kinds of furan derivatives.

CCDC 821778: Experimental Crystal Structure Determination

Related Article: Hui Li, Fu-Min Zhang, Yong-Qiang Tu, Qing-Wei Zhang, Zhi-Min Chen, Zhi-Hua Chen, Jian Li|2011|Chemical Science|2|1839|doi:10.1039/c1sc00295c