title: Regiocomplementary cycloaddition reactions of boryl- and silylbenzynes with 1,3-dipoles: selective synthesis of benzo-fused azole derivatives.
abstract: Benzo-fused nitrogen-containing heterocycles are abundant in biologically active compounds. One of the most important methods for preparing such heterocycles is the (3 + 2) cycloaddition reaction of benzynes with 1,3-dipolar compounds. However, the reactions of unsymmetrically substituted benzynes generally show low selectivity and hence yield mixtures of two regioisomers. In this paper, we describe the synthesis of both regioisomers of multisubstituted benzo-fused azole derivatives such as benzotriazoles, 1H-indazoles, and benzo[d]isoxazoles through the regiocomplementary (3 + 2) cycloaddition reactions of 3-boryl- and 3-silylbenzynes with 1,3-dipoles. The improved generation of 3-borylbenzynes from new precursors was one of the most important results of this work, which produced the successful (3 + 2) cycloaddition reactions with exclusive and proximal selectivities. On the other hand, similar reactions of 3-silylbenzynes selectively afforded distal cycloadducts. Analysis of the reaction pathways of these amazing regioselectivities by density functional theory calculations revealed that the (3 + 2) cycloadditions of borylbenzynes are controlled by the electrostatic effect of the boryl group, while those of silylbenzynes are controlled mainly by the steric effect of the bulky silyl groups that produced electrostatically unfavorable adducts via anomalous transition states.
authors: School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan.
authors: Takashi
authors: T
authors: Ikawa
authors: Akira
authors: A
authors: Takagi
authors: Masahiko
authors: M
authors: Goto
authors: Yuya
authors: Y
authors: Aoyama
authors: Yoshinobu
authors: Y
authors: Ishikawa
authors: Yuji
authors: Y
authors: Itoh
authors: Satoshi
authors: S
authors: Fujii
authors: Hiroaki
authors: H
authors: Tokiwa
authors: Shuji
authors: S
authors: Akai
mesh_terms: D001386:Azides / Q000737:chemistry*; D001393:Azoles / Q000138:chemical synthesis* / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D001386:Azides; D001393:Azoles; D001555:Benzene Derivatives; C524146:benzyne