T2 - Chemistry of Heterocyclic Compounds

N2 - We disclose an efficient and operationally simple protocol for the preparation of fused N-heterocycles starting from readily available 2-nitrobiaryls and PhMgBr under mild conditions. More than two dozen N-heterocycles, including two bioactive natural products, have been synthesized using this method. A stepwise electrophilic aromatic cyclization mechanism was proposed by DFT calculations. Controlled fusion: A transition-metal-free, low-temperature, and regioselective intramolecular amination of aromatic C(sp2)-H bonds provides fused N-heterocycles. This reaction is operationally simple and scalable (1-10 mmol) and the scope of substrates is wide (see scheme). Density functional calculations indicate that a stepwise electrophilic aromatic cyclization mechanism may be operative.

T1 - Synthesis of fused heterocycles via Pd-catalyzed multiple aromatic C-H activation reactions

Therefore we were inspired to work on the development of new synthetic methodologies for thio- and furan-fused heterocycles. Starting from diacid 7 , we aimed here to prepare of the furopyranone 8 and furopyrrolone 9 derivatives ( Scheme 1 ).


JF - Chemistry of Heterocyclic Compounds

Fusing furan rings with other heterocycles results in new characteristics. Furopyranones ( 4 ) and furopyrrolones ( 5 ) are key examples of furan-fused heterocyclic systems that have crucial roles ( Fig. 2 ). 10–14 For instance neo-tanshinlactone ( 6 ), a furopyranone derivative, is reported to be 20 times more selective than antiestrogenic tomoxifen citrate, which is clinically used in breast cancer therapies. 15


Synthesis Of Fused Heterocycles Volume 47 Part 1

AB - We disclose an efficient and operationally simple protocol for the preparation of fused N-heterocycles starting from readily available 2-nitrobiaryls and PhMgBr under mild conditions. More than two dozen N-heterocycles, including two bioactive natural products, have been synthesized using this method. A stepwise electrophilic aromatic cyclization mechanism was proposed by DFT calculations. Controlled fusion: A transition-metal-free, low-temperature, and regioselective intramolecular amination of aromatic C(sp2)-H bonds provides fused N-heterocycles. This reaction is operationally simple and scalable (1-10 mmol) and the scope of substrates is wide (see scheme). Density functional calculations indicate that a stepwise electrophilic aromatic cyclization mechanism may be operative.

Synthesis of spiro-fused pyrazolidoylisoxazolines — …

AB - Routes to structurally unique spiro-fused pyrazolidoylisoxazolines are reported. These methods start with monosubstituted hydrazines or hydrazides and utilize the nitrile oxide 1,3-dipolar cycloaddition reaction to generate the targeted spiro-fused bis-heterocycles. Molecular shape space diversity analyses were performed on these pyrazolidoylisoxazolines showing that manipulation of the appended R groups significantly changes the molecular shape.

reaction to generate the targeted spiro-fused bis-heterocycles

Inspired by the tautomeric relationship of imidazole and N-heterocyclic carbenes, we have been intrigued about the implications of such carbenes in metalloenzymes. Enzymes are the machinery of all biological transformations, and provide inspiration for designing artificial catalysts. New insights into the mode of action of enzymes is therefore instrumental for developing more competent synthetic catalysts as well as for better understanding natural systems. In collaboration with F. Paradisi (U Nottingham), we have begun to explore carbene binding to metalloenzymes. We have been focusing on blue copper proteins such as azurin and specific mutants of azurin to investigate the possibility of carbene bonding to the copper center, and to evaluate the effect that such bonding entails. While azurin is predominantly involved in electron transfer processes through reversible copper(II) reduction and oxidation, other blue copper proteins are catalytically active in redox transformations of substrates. Hence, these enzymes provide an attractive probe to explore the relevance of carbene bonding on the catalytic performance of the enzyme.

Fused polycyclic nitrogen-containing heterocycles: IX

N2 - Routes to structurally unique spiro-fused pyrazolidoylisoxazolines are reported. These methods start with monosubstituted hydrazines or hydrazides and utilize the nitrile oxide 1,3-dipolar cycloaddition reaction to generate the targeted spiro-fused bis-heterocycles. Molecular shape space diversity analyses were performed on these pyrazolidoylisoxazolines showing that manipulation of the appended R groups significantly changes the molecular shape.