Enantioselective Isocyanide-based Multicomponent Reaction with Alkylidene Malonates and Phenols

Abstract

A highly enantioselective isocyanide-based multicomponent reaction catalyzed by a chiral N,N′-dioxide/MgII complex was reported. A wide range of substrates were tolerated in this reaction, including alkyl- and aryl-substituted isocyanides with alkylidene malonates and various phenols, affording the corresponding phenoxyimidate products in good to excellent yields (up to 94% yield) with good to excellent enantioselectivities (up to 95.5:4.5 er). A catalytic cycle and transition state were proposed to rationalize the reaction process and enantiocontrol.

Enantioselective Synthesis of Azetidines through [3 + 1]-Cycloaddition of Donor–Acceptor Aziridines with Isocyanides

“…In continuation of our interest in asymmetric cycloadditions of aziridines, we wondered whether they could undergo 1,3-dipolar cycloaddition with an appropriate one-carbon source, such as isocyanides, , the transformation of which has been reported in as early as 1975, to realize the enantioselective synthesis of optically functionalized azetidines. Nevertheless, the nature of isocyanides makes it inevitable for the competitive reactions between [3 + 1]-cycloaddition and [3 + 1 + 1]-cycloaddition, as well as acyclic byproducts of other nucleophiles .…”

Recent Developments in Enantioselective Domino Reactions. Part B: First Row Metal Catalysts

“…Later in 2021, Feng and Cao also applied this catalyst system at 10 mol% of catalyst loading to promote enantioselective three-component reaction between alkylidene malonates 216, isocyanides 217 and phenols 221. [68] In this case, the reaction was performed at 0 or À 20 °C in PhCF 3 as solvent in the presence of tri(n-pentyl)amine as base, delivering the corresponding chiral phenoxyimidates 222 with good to high yields (59-90%) and enantioselectivities (85-90% ee), as presented in Scheme 56. Both alkyl-and aryl-substituted isocyanides were tolerated as well as differently substituted alkylidene malonates and phe-nols spanning from 1-and 2-naphthols to more simple phenols.…”

Catalytic Approaches to Multicomponent Reactions: A Critical Review and Perspectives on the Roles of Catalysis

“…When considering enantioselective MCRs, however, there is a huge gap between homogeneous and heterogeneous catalyzed reactions. A plethora of successfully performed multicomponent syntheses under homogeneous catalysis can be found in the literature [ 178 , 186 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 ], whereas heterogeneous reactions are not.…”