Xianxiu Xu

Double Isocyanide Cyclization: A Synthetic Strategy for Two-Carbon-Tethered Pyrrole/Oxazole Pairs

A new strategy for the construction of the compounds with two different heterocycles, linked by a C(2)-tether via a domino process involving [5 + 1] annulation, ring-opening, and subsequent double isocyanide cyclization, from the reaction of ethyl isocyanoacetate with divinyl ketones (DVKs) has been developed. The chemoselective fragmentation of the cyclohexanone intermediate is the key for the formation of not only the C(2)-tether but also the two different heterocycles.

Tandem Double-Michael-Addition/Cyclization/Acyl Migration of 1,4-Dien-3-ones and Ethyl Isocyanoacetate : Stereoselective Synthesis of Pyrrolizidines

Up to four adjacent stereocenters can be formed stereoselectively in the construction of a pyrrolizidine unit through a novel organocatalytic reaction that involves treatment of various dienones with ethyl isocyanoacetate (see scheme; DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene). Mechanisms for this atom-economic, one-pot synthesis have been proposed.

Facile [7C+1C] Annulation as an Efficient Route to Tricyclic Indolizidine Alkaloids

The indolizidine skeleton is one of the most important structural motifs found in numerous biologically active molecules. The development of efficient methods for the synthesis of indolizidine alkaloids has been the subject of intense research. Recently, we have been devoted to the research of heterocyclizations using alkenoyl ketene dithioacetals as five-carbon 1,5-dielectrophiles 6] and ethyl isocyanoacetate as both a double Michael donor and a 1,3-dipole in a [5C+1C] annulation process for the construction of complex heterocyclic systems (Scheme 1). As part of our studies in this area, we herein report a new synthetic strategy for the construction of the tricyclic indolizidine alkaloids 3 by an unprecedented [7C+1C] annulation to deliver the 8azabicyclo[5.2.1]dec-8-enes 2 from the easily available dialkenoyl ketene dithioacetals 1 as C7 1,7-dielectrophiles (Scheme 1). Initially, the reaction of the dialkenoyl ketene dithioacetal 1a with ethyl isocyanoacetate was investigated to evaluate a tandem process involving a [7C+1C] annulation with 1a as a C7 1,7-dielectrophile (Table 1). It was found that treatment

Rhodium(III)-catalyzed intramolecular amidoarylation and hydroarylation of alkyne via C-H activation: switchable synthesis of 3,4-fused tricyclic indoles and chromans.

The controllable intramolecular amidoarylation and hydroarylation of alkynes has been achieved via rhodium(III)-catalyzed C-H activation. The merger of two distinct reaction pathways allows for the development of atom- and step-economic protocols for the switchable synthesis of 3,4-fused indoles and chromans, respectively.

Chemistry of Ketene N,S-Acetals: An Overview

Push-pull alkenes, which bear electron-donating and -accepting group(s) at both termini of a C═C double bond, respectively, are of interest not only for their unique electronic properties but also for their importance as versatile building blocks in organic synthesis. In the world of ketene acetals having the push-pull alkene skeleton, ketene N,S-acetal is most likely the biggest family according to the number and types of these compounds. The first ketene N,S-acetal compound was reported in 1956. As a cyclic ketene N,S-acetal compound, nithiazine, the first lead structure of neonicotinoid insecticides, was reported in 1978. The characteristics of ketene N,S-acetals, which have the structural feature of ketene S,S-acetals and enaminones, make them versatile and easy to use, especially in cyclization and multicomponent reactions for the synthesis of various heterocyclic systems and related natural products. There has been an increasing wealth of information about the synthesis and synthetic applications of ketene N,S-acetals, especially, in recent years. This review provides comprehensive knowledge on the chemistry of ketene N,S-acetals.

3+3 -cycloaddition reactions of α-acidic isocyanides with 1,3-dipolar azomethine imines

α-Acidic isocyanides are versatile reagents in organic synthesis, especially for the synthesis of five-membered heterocycles via [3 + 2]-cycloaddition reactions with activated multiple bonds. In this communication, the first [3 + 3]-cross-cycloaddition of α-acidic isocyanides with 1,3-dipolar azomethine imines to generate a series of 1,2,4-triazine derivatives with significant regiochemical control under mild catalytic reaction conditions is described. This new strategy shows that α-acidic isocyanides can also be taken as potent reagents for the synthesis of six-membered heterocycles through [3 + 3]-cross-cycloaddition reactions with 1,3-dipoles.

Hydroxyamination of aryl C–H bonds with N-hydroxycarbamate by synergistic Rh/Cu catalysis at room temperature

A novel hydroamination of aryl C-H bonds has been accomplished using N-Boc-hydroxyamine via synergistic combination of rhodium and copper catalysis. The merger of two robust catalytic systems has allowed for the development of a mild and sustainable protocol for the direct formation of benzo[c]isoxazol-3(1H)-ones.

Tandem Michael addition/isocyanide insertion into the C–C bond: a novel access to 2-acylpyrroles and medium-ring fused pyrroles

A new reaction model, tandem Michael addition/formal isocyanide insertion into the acyl C-C bond, has been developed. Thus, a series of 2-acylpyrroles and seven-/eight-membered ring fused pyrroles were synthesized from the reaction of methyl isocyanides with enones in a single operation.

Cross‐Cycloaddition of Two Different Isocyanides: Chemoselective Heterodimerization and [3+2]‐Cyclization of 1,4‐Diazabutatriene

A new cross-cycloaddition reaction between a wide range of isocyanides and 2-isocyanochalcones (or analogues) was developed for the expeditious synthesis of pyrrolo[3,4-b]indoles under thermal conditions. On the basis of the experimental results and DFT calculations, a mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides to form 1,4-diazabutatriene intermediates, followed by an intramolecular [3+2]-cycloaddition and 1,3-proton shift.

Polarity-Reversible Conjugate Addition Tuned by Remote Electronic Effects

A new concept, polarity-reversible conjugate addition, has been described, based on the findings that the polarity of a classical Michael acceptor can be reversed through remote electronic effects. In addition, the remote electronic effects are tunable, and both five- and six-membered nitrogen rings can be constructed starting from acyclic precursors having the same enone structure unit simply by varying a remote substituent in the molecules.