Asymmetric Multicomponent Reactions Based on Trapping of Active Intermediates

Abstract

Metal carbenes derived from transition metal-catalyzed decomposition of diazo compounds react with nucleophiles with heteroatoms, such as alcohols and amines, to generate highly active oxonium/ammonium ylides intermediates. These intermediates can be trapped by appropriate electrophiles to provide three-component products. Based on this novel trapping process, we have developed novel multicomponent reactions (MCRs) of diazo compounds, alcohols/anilines, and electrophiles. The nucleophiles were also extended to electron-rich heterocycles (indoles and pyrroles)/arenes, in which the resulting zwitterionic intermediates were also trapped by electrophiles. By employing efficient catalysis strategy, the reactions were realized with excellent stereocontrol and wide substrate scope. In this personal account, we introduce our breakthroughs in the development of novel asymmetric MCRs via trapping of the active ylides and zwitterionic intermediates with a number of electrophiles, such as imines, aldehyde, and Michael acceptors, under asymmetric catalysis. Transition metal/chiral Lewis acid catalysis, transition metal/Brønsted acid catalysis, and chiral transition-metal catalysis, enable excellent stereocontrolled outcomes. The methodologies not only provide experimental evidence to support the existence of protic onium ylides intermediates/zwitterionic intermediates and the stepwise pathways of carbene-induced O-H, N-H and C-H insertions, but also offer a novel approach for the efficient construction of chiral polyfunctional molecules.

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

“…In recent years, metal carbene-involved multicomponent reactions (MCRs) based on electrophilic trapping of active onium ylides have emerged as a powerful strategy to enable previously inefficient or even impossible chemical transformations [37][38][39][40][41][42][43][44] . Among them, the Mannich-type trapping of oxonium ylides with aryl imines has offered a rapid way for the synthesis of β-amino alcohols [45][46][47][48] .…”

Synergistic‐Catalysis‐Enabled Reaction of 2‐Indolymethanols with Oxonium Ylides for the Construction of 3‐Indolyl‐3‐Alkoxy Oxindole Frameworks

“…Although CPAs 6j-6k and 6m did catalyzet he reaction, their enantioselectivities were still extremely low ( Table 4, entry [10][11]13). Next, we investigated the effect of reaction temperature in the presence of CPA 6a ( Table 4, entries [15][16][17]. Elevating the reactiont emperature from 30 8Cto508Cled to asharp decrease in enantioselectivity ( Table 4, entry 1v s. entry 15).…”

“…Among the variousm etal-associated ylides, onium ylides, which contain both acidic protons and basic carbanions in vicinal proximity to one another,have recently been recognized as activen ucleophiles that can be trapped by electrophiles (Scheme 3). [15] Onium ylides are generated in situ from diazo compounds and anilines/alcohols. Elegant reactions have been reported in this field that use aldimines, carbonyl compounds, and activateda lkenes as electrophiles [Eq.…”

“…(5)]. [15,16] However,t he reactions betweeno nium ylides and aryl electrophiles are still underdeveloped [Eq. (6)].…”

Synthesis of a novel and reusable biological urea based acidic nanomagnetic catalyst: Application for the synthesis of 2‐amino‐3‐cyano pyridines via cooperative vinylogous anomeric based oxidation

“…[41][42][43][44][45][46][47] The concept of anomeric effect is one of the most influential domain of stereoelectronic effects which intensively studied. Multicomponent reactions routs provide valuable conceptual and synthetic merits compare with stepwise sequential protocols for the preparation of complex structures through a cost-effective method.…”