Oligosubstituted Pyrroles Directly from Substituted Methyl Isocyanides and Acetylenes

The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3. The scope and limitations of this reaction (24 examples, 25–97 % yield) are reported along with an optimiz...

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Published inChemistry : a European journal Vol. 15; no. 1; pp. 227 - 236
Main Authors Lygin, Alexander V., Larionov, Oleg V., Korotkov, Vadim S., de Meijere, Armin
Format Journal Article
LanguageEnglish
Published Weinheim WILEY‐VCH Verlag 01.01.2009
Wiley
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Abstract The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3. The scope and limitations of this reaction (24 examples, 25–97 % yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. In addition, a related newly developed CuI‐mediated synthesis of 2,3‐disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides is described (11 examples, 5–88 %yield). Convenient pyrrole syntheses: Two new protocols have been developed for one‐pot, one‐step formal [3+2] cycloadditions of substituted methyl isocyanides onto the triple bond of either acceptor‐activated internal or non‐activated terminal acetylenes leading to 2,3,4‐trisubstituted and 2,3‐disubstituted pyrroles, respectively (see scheme).
AbstractList The formal cycloaddition of alpha-metallated methyl isocyanides 1 onto the triple bond of electron-deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3. The scope and limitations of this reaction (24 examples, 25-97% yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. in addition, it related newly developed Cu-1-mediated synthesis of 2.3-disubstituted pyrrole by the reaction of copper acetylides derived from unactivated terminal alkynes with Substituted methyl isocyanides is described (11 examples, 5-88% yield).
The formal cycloaddition of alpha-metallated methyl isocyanides 1 onto the triple bond of electron-deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3. The scope and limitations of this reaction (24 examples, 25-97% yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. In addition, a related newly developed Cu(I)-mediated synthesis of 2,3-disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides is described (11 examples, 5-88% yield).
Abstract The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3 . The scope and limitations of this reaction (24 examples, 25–97 % yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. In addition, a related newly developed Cu I ‐mediated synthesis of 2,3‐disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides is described (11 examples, 5–88 %yield).
The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3. The scope and limitations of this reaction (24 examples, 25–97 % yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. In addition, a related newly developed CuI‐mediated synthesis of 2,3‐disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides is described (11 examples, 5–88 %yield). Convenient pyrrole syntheses: Two new protocols have been developed for one‐pot, one‐step formal [3+2] cycloadditions of substituted methyl isocyanides onto the triple bond of either acceptor‐activated internal or non‐activated terminal acetylenes leading to 2,3,4‐trisubstituted and 2,3‐disubstituted pyrroles, respectively (see scheme).
Author Korotkov, Vadim S.
de Meijere, Armin
Lygin, Alexander V.
Larionov, Oleg V.
Author_xml – sequence: 1
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  surname: de Meijere
  fullname: de Meijere, Armin
  email: ameijer1@gwdg.de
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Issue 1
Keywords 1,3-DIPOLAR CYCLOADDITIONS
INSERTION
ASYMMETRIC-SYNTHESIS
SYNTHETIC REACTIONS
catalysis
ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS
TERMINAL ALKYNES
pyrroles
isocyanides
cycloaddition
COMPLEX CATALYSTS
DNA GYRASE
copper
MULTICOMPONENT SYNTHESIS
ALPHA-METALATED ISOCYANIDES
Language English
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Publisher WILEY‐VCH Verlag
Wiley
Publisher_xml – name: WILEY‐VCH Verlag
– name: Wiley
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1968; 9
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2002 2002; 114 41
1997; 119
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Snippet The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and convenient...
The formal cycloaddition of alpha-metallated methyl isocyanides 1 onto the triple bond of electron-deficient acetylenes 2 represents a direct and convenient...
Abstract The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and...
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SubjectTerms Alkynes - chemistry
Catalysis
Chemistry
Chemistry, Multidisciplinary
copper
Copper - chemistry
Cyanides - chemical synthesis
Cyanides - chemistry
cycloaddition
isocyanides
Physical Sciences
pyrroles
Pyrroles - chemical synthesis
Pyrroles - chemistry
Science & Technology
Title Oligosubstituted Pyrroles Directly from Substituted Methyl Isocyanides and Acetylenes
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fchem.200801395
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https://www.ncbi.nlm.nih.gov/pubmed/19025729
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