Radical and Ionic Reactions of Indolizin-1-ols: Synthesis of 3-Arylsulfanyl-, 3-(Tropon-2-yl)- and 3-(Tropolon-5-ylazo)-1-hydroxyindolizines from 3,3-Difluorocyclopropenes

Abstract

An aerobic multicomponent reaction between monoalkyl-3,3-difluorocyclopropenes, pyridines, and arylthiols has been discovered to afford 3-arylsulfanyl-1-hydroxyindolizines. This reaction proceeds via intermediate C3-free indolizin-1-ols, easily forming free radicals in air. In the presence of arylthiols, potent radical traps, incorporation of arylsulfanyl substituent occurs at the C3 position of indolizin-1-ols by radical recombination. On the contrary, in an inert atmosphere, intermediate 1-hydroxyindolizines react with C-and N-electrophiles in a one-pot fashion. Novel, intensively colored 3-(tropon-2-yl)-indolizin-1-ols and high absorption coefficient 3-(tropolon-5-ylazo)-indolizin-1-ol dyes were synthesized in a multicomponent manner in 50−80% yields. The presence of an O-uncapped indolizin-1-ol moiety modulates the redox properties of the whole molecule, facilitating free radical formation, which is susceptible to further transformations. Three such examples were demonstrated: oxidative recyclization of 3-(2hydroxyphenylsulfanyl)-indolizin-1-ol, auto-oxidation of substituted 3,3′-biindolizine-1,1′-diol, and diacetoxyiodobenzene (DAIB)mediated dehydrogenation of 3-(tropolon-5-ylazo)-indolizin-1-ol. The latter reaction affords 3-((4,5-dioxocyclohepta-2,6-dien-1ylidene)hydrazono)-3H-indolizin-4-ium-1-olate, a mesomeric betaine, strongly absorbing light on the borders of the visible range and showing a solvatochromic effect.

Multiple-fold C–F bond functionalization for the synthesis of (hetero)cyclic compounds: fluorine as a detachable chemical handle

“…71 Very recently, cyclopentenone and N -methylmaleimide were also introduced as Michael acceptors for the flexible installation of alkyl functional group at C3 position of indolizin-1-ols (Scheme 36d). 72 The double bond in air-sensitive product 36-10 could be easily restored in near-quantitative yield by aerobic dehydrogenation. In all of these independent entries, similar observations are powerful complements with their previous conclusions that: (1) 3,3-difluorocyclopropene is sufficiently activated by the CF 2 moiety in favor of its cyclization with pyridines; (2) in situ generated C3-free 1-hydrozyindolizines are easily transformed to C3-radical species under air; (3) the reaction efficiency is dramatically determined by the substituents on the pyridines.…”

Deconstructive Cycloaromatization Strategy toward N,O-Bidentate Ligands from Indolizines and Cyclopropenones

“…A reasonable mechanism is depicted in Scheme 6 on the basis of the current results and previous reports. 15 In conclusion, we have developed an efficient and unprecedented route for producing novel polyaryl N,Obidentate ligands via deconstructive cycloaromatization from indolizines and cyclopropenones without any catalysts. In addition, a series of N,O-bidentate organic BF 2 complexes can also be constructed via this one-pot protocol.…”

“…A reasonable mechanism is depicted in Scheme on the basis of the current results and previous reports . First, cyclopropenone 2a transformed into its synthetic equivalent 1,3-dipole I , which reacts with 2-phenyl indolizine 1a at high temperature to give intermediate II .…”

3-Thioxo-3H-indolizinium-1-olates and Related Pseudo-Cross-Conjugated Heterocyclic Mesomeric Betaines: Synthesis and Spectral Features

“…Recently we reported a number of studies − on the chemistry of highly reactive C3-unsubstituted indolizin-1-ols. In our approach, we utilized an accidently discovered reaction of pyridines and mono substituted 3,3-difluorocyclopropenes in wet nonbasic solvents which resulted in C3-free indolizin-1-ols.…”