The Use of Electrophilic Cyclization for the Preparation of Condensed Heterocycles

Condensed heterocycles are well-known for their excellent biological effects and they are undeniably important compounds in organic chemistry. Electrophilic cyclization reactions are widely used for the synthesis of mono-heterocyclic compounds. This review highlights the utility of electrophilic cyclization reactions as an effective generic tool for the synthesis of various condensed heterocycles containing functional groups that are able to undergo further chemical transformations, such as nucleophilic substitution, elimination, re-cyclization, cleavage, etc. This review describes the reactions of unsaturated derivatives of different heterocycles with various electrophilic agents (halogens, arylsulfanyl chlorides, mineral acids) resulting in annulation of an additional partially saturated heterocycle. The electrophilic reaction conditions, plausible mechanisms and the use of such transformations in organic synthesis are also discussed. The review mainly focuses on research published since 2002 in order to establish the current state of the art in this area. 1 Introduction2 Electrophilic Cyclization Pathways Involving a Nitrogen Nucleo­philic Center3 Electrophilic Cyclization Pathways Involving a Chalcogen Nucleophilic Center3.1 Sulfur Centers3.2 Oxygen Centers3.3 Selenium Centers4 Strategies and Mechanisms5 Conclusion

Biomimetic hydrogen-bonding cascade for chemical activation: telling a nucleophile from a base

Biomimetic cascade hydrogen bonds promote covalent capture of a nucleophile by polarizing the electrophilic reaction site, while suppressing non-productive acid–base chemistry as the competing reaction pathway.

m-Carborane as a Novel Core for Periphery-Decorated Macromolecules

Closo m-C2B10H12 can perform as a novel core of globular periphery-decorated macromolecules. To do this, a new class of di and tetrabranched m-carborane derivatives has been synthesized by a judicious choice of the synthetic procedure, starting with 9,10-I2-1,7-closo-C2B10H10. The 2a-NPA (sum of the natural charges of the two bonded atoms) value for a bond, which is defined as the sum of the NPA charges of the two bonded atoms, matches the order of electrophilic reaction at the different cluster bonds of the icosahedral o-and m- carboranes that lead to the formation of B-I bonds. As for m-carborane, most of the 2a-NPA values of B-H vertexes are positive, and their functionalization is more challenging. The synthesis and full characterization of dibranched 9,10-R2-1,7-closo-carborane (R = CH2CHCH2, HO(CH2)3, Cl(CH2)3, TsO(CH2)3, C6H5COO(CH2)3, C6H5COO(CH2)3, N3(CH2)3, CH3CHCH, and C6H5C2N3(CH2)3) compounds as well as the tetrabranched 9,10-R2-1,7-R2-closo-C2B10H8 (R = CH2CHCH2, HO(CH2)3) are presented. The X-ray diffraction of 9,10-(HO(CH2)3)2-1,7-closo-C2B10H10 and 9,10-(CH3CHCH)2-1,7-closo-C2B10H10, as well as their Hirshfeld surface analysis and decomposed fingerprint plots, are described. These new reported tetrabranched m-carborane derivatives provide a sort of novel core for the synthesis of 3D radially grown periphery-decorated macromolecules that are different to the 2D radially grown core of the tetrabranched o-carborane framework.

The Product Specificities of Maize Terpene Synthases TPS4 and TPS10 Are Determined Both by Active Site Amino Acids and Residues Adjacent to the Active Site

Terpene synthases make up a large family of enzymes that convert prenyl diphosphates into an enormous variety of terpene skeletons. Due to their electrophilic reaction mechanism—which involves the formation of carbocations followed by hydride shifts and skeletal rearrangements—terpene synthases often produce complex mixtures of products. In the present study, we investigate amino acids that determine the product specificities of the maize terpene synthases TPS4 and TPS10. The enzymes showed 57% amino acid similarity and produced different mixtures of sesquiterpenes. Sequence comparisons and structure modeling revealed that out of the 43 amino acids forming the active site cavity, 17 differed between TPS4 and TPS10. While combined mutation of these 17 residues in TPS4 resulted in an enzyme with a product specificity similar to TPS10, the additional mutation of two amino acids next to the active site led to a nearly complete conversion of TPS4 into TPS10. These data demonstrate that the different product specificities of TPS4 and TPS10 are determined not only by amino acids forming the active site cavity, but also by neighboring residues that influence the conformation of active site amino acids.

cis or trans with class II diterpene cyclases

Isoprenoid precursors readily undergo (poly)cyclization in electrophilic reaction cascades, presumably as internal addition of the carbon–carbon double-bonds from neighboring isoprenyl repeats readily forms relatively stable cyclohexyl tertiary carbocation intermediates.