TY - JOUR

T1 - Stereo- and Regioselective 1,3-Dipolar Cycloaddition of the Stable Ninhydrin-Derived Azomethine Ylide to Cyclopropenes

T2 - Trapping of Unstable Cyclopropene Dipolarophiles

AU - Filatov, Alexander S.

AU - Wang, Siqi

AU - Khoroshilova, Olesya V.

AU - Lozovskiy, Stanislav V.

AU - Larina, Anna G.

AU - Boitsov, Vitali M.

AU - Stepakov, Alexander V.

N1 - Publisher Copyright: © 2019 American Chemical Society. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/6/7

Y1 - 2019/6/7

N2 - A stereo- and regioselective 1,3-dipolar cycloaddition of the stable ninhydrin-derived azomethine ylide [2-(3,4-dihydro-2H-pyrrolium-1-yl)-1-oxo-1H-inden-3-olate, DHPO] to differently substituted cyclopropenes has been established. As a result, an efficient synthetic protocol was developed for the preparation of biologically relevant spiro[cyclopropa[a]pyrrolizine-2,2′-indene] derivatives. DHPO has proved to be an effective trap for such highly reactive and unstable substrates as parent cyclopropene, 1-methylcyclopropene, 1-phenylcyclopropene, and 1-halo-2-phenylcyclopropenes. It has also been found that 3-nitro-1,2-diphenylcyclopropene undergoes a nucleophilic substitution reaction in alcohols and thiols to afford 3-alkoxy- and 3-arylthio-substituted 1,2-diphenylcyclopropenes, which can be captured as corresponding 1,3-dipolar cycloadducts in the presence of DHPO. These new approaches provide a straightforward strategy for the synthesis of functionally substituted cyclopropa[a]pyrrolizine derivatives. The factors governing regio- and stereoselectivity have been revealed by means of quantum mechanical calculations (M11 density functional theory), including previously unreported Nylide-Hcyclopropene second-orbital interactions. The outcome of this work contributes to the study of 1,3-dipolar cycloaddition, as well as enriches chemistry of cyclopropenes and methods for the construction of polycyclic compounds with cyclopropane fragments.

AB - A stereo- and regioselective 1,3-dipolar cycloaddition of the stable ninhydrin-derived azomethine ylide [2-(3,4-dihydro-2H-pyrrolium-1-yl)-1-oxo-1H-inden-3-olate, DHPO] to differently substituted cyclopropenes has been established. As a result, an efficient synthetic protocol was developed for the preparation of biologically relevant spiro[cyclopropa[a]pyrrolizine-2,2′-indene] derivatives. DHPO has proved to be an effective trap for such highly reactive and unstable substrates as parent cyclopropene, 1-methylcyclopropene, 1-phenylcyclopropene, and 1-halo-2-phenylcyclopropenes. It has also been found that 3-nitro-1,2-diphenylcyclopropene undergoes a nucleophilic substitution reaction in alcohols and thiols to afford 3-alkoxy- and 3-arylthio-substituted 1,2-diphenylcyclopropenes, which can be captured as corresponding 1,3-dipolar cycloadducts in the presence of DHPO. These new approaches provide a straightforward strategy for the synthesis of functionally substituted cyclopropa[a]pyrrolizine derivatives. The factors governing regio- and stereoselectivity have been revealed by means of quantum mechanical calculations (M11 density functional theory), including previously unreported Nylide-Hcyclopropene second-orbital interactions. The outcome of this work contributes to the study of 1,3-dipolar cycloaddition, as well as enriches chemistry of cyclopropenes and methods for the construction of polycyclic compounds with cyclopropane fragments.

UR - http://www.scopus.com/inward/record.url?scp=85066949598&partnerID=8YFLogxK

U2 - 10.1021/acs.joc.9b00753

DO - 10.1021/acs.joc.9b00753

M3 - Article

C2 - 31066276

AN - SCOPUS:85066949598

VL - 84

SP - 7017

EP - 7036

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 11

ER -