[2+2+2] Cycloadditions of Alkynes with Heterocumulenes and Nitriles

Abstract

[2+2+2] Cycloadditions of heterocumulenes and nitriles represent an efficient, atom‐economical method of synthesizing heterocycles and, to a lesser extent, carbocycles. Cycloadditions of heterocumulenes including isocyanates, carbodiimides, carbon dioxide, carbon disulfide, ketenes, as well as nitriles are explored. The heterocumulene is typically coupled with an alkyne or diyne, forming 6‐membered heterocycles, although multiple heterocumulenes are sometimes incorporated. The reactions are generally catalyzed by late‐transition‐metal catalysts, albeit nucleophilic catalysts and early‐transition metals are sometimes used. [2+2+2]; cycloaddition; heterocumulene; isocyanate; carbodiimide; carbon dioxide; carbon disulfide; ketene; nitrile; alkyne; diyne; pyridone; pyridine; transition‐metal catalysis

Rolf Huisgen's Classic Studies of Cyclic Triene Diels–Alder Reactions Elaborated by Modern Computational Analysis

“…4] exemplifies one such reaction discovered by R. C. Cookson et al . An enormous body of literature on thermal and metal‐catalyzed [2+2+2] cycloadditions and even genetically‐encoded [2+2+2] cycloadditions is now available.…”

o‐Quinodimethane Atropisomers: Enantioselective Synthesis and Stereospecific Transformation

“…[9] Cross‐coupling reactions, [10] transformations of stereodynamic biaryl systems, [11] the functionalization of biaryl scaffolds [12] and stereoselective arene formation [13] thereby emerged as comprehensive strategies. Among these methods, the transition‐metal‐catalyzed arene‐forming [2+2+2] cycloaddition was found to be particularly versatile for the synthesis of unusually congested products[ 13e , 13f , 13g , 13h , 13i , 13j , 13k , 13l , 13m ] and especially chiral rhodium(I) catalysts enabled an excellent efficiency and selectivity for the enantioselective synthesis of atropisomeric biaryls from functionalized triynes. [14] Prior to these enantioselective [2+2+2] cycloadditions, Funk and Vollhardt disclosed a seminal total synthesis of (±)‐estrone by combining a [2+2+2] cycloaddition with a subsequent Diels–Alder reaction through a corresponding o ‐QDM (Figure 1 B).…”

o‐Quinodimethane Atropisomers: Enantioselective Synthesis and Stereospecific Transformation

“…Cross‐coupling reactions, [10] transformations of stereodynamic biaryl systems, [11] the functionalization of biaryl scaffolds [12] and stereoselective arene formation [13] thereby emerged as comprehensive strategies. Among these methods, the transition‐metal‐catalyzed arene‐forming [2+2+2] cycloaddition was found to be particularly versatile for the synthesis of unusually congested products [13e–m] and especially chiral rhodium(I) catalysts enabled an excellent efficiency and selectivity for the enantioselective synthesis of atropisomeric biaryls from functionalized triynes [14] . Prior to these enantioselective [2+2+2] cycloadditions, Funk and Vollhardt disclosed a seminal total synthesis of (±)‐estrone by combining a [2+2+2] cycloaddition with a subsequent Diels–Alder reaction through a corresponding o ‐QDM (Figure 1B) [4a] .…”