Rhodium‐Catalyzed Asymmetric N−H Functionalization of Quinazolinones with Allenes and Allylic Carbonates: The First Enantioselective Formal Total Synthesis of (−)‐Chaetominine

Abstract

An unprecedented asymmetric N-H functionalization of quinazolinones with allenes and allylic carbonates was successfully achieved by rhodium catalysis with the assistance of chiral bidentate diphosphine ligands. The high efficiency and practicality of this method was demonstrated by a low catalyst loading of 1 mol % as well as excellent chemo-, regio-, and enantioselectivities with broad functional group compatibility. Furthermore, this newly developed strategy was applied as key step in the first enantioselective formal total synthesis of (-)-chaetominine.

Rhodium-Catalyzed Allylation Reactions

“…This chemo-, regio-, and enantioselective method was further utilized for the formal total synthesis of (-)-chaetominine. 63…”

“…Furthermore, the total synthesis of (S)-ibuprofen, 12 (-)sugiresinol, and (R)-ruxolitinib, 58 and formal synthesis of putaminoxin E, 68 (-)-chaetominine, 63 (+)-testosterone acetate, 52 and glucokinase activators, 56 etc. also showed the utility of enantioselective Rh-catalyzed allylation reactions as a key step in synthesis of natural products and bioactive molecules.…”

Catalytic asymmetric synthesis of geminal-dicarboxylates

“…A variety of rhodium-catalysed asymmetric allylation-type processes, including allylic substitutions, with oxygen, nitrogen and carbon nucleophiles have been reported to form allylic alcohols, amines, and tertiary or quaternary carbon stereogenic centers. 30 – 39 Carboxylic acids may be used as nucleophiles, not only in rhodium-catalysed asymmetric reactions, 40 but also in processes catalysed by iridium, 41 palladium, 42 , 43 and ruthenium. 44 However, only limited examples of metal-catalysed asymmetric additions to make stereogenic centres bearing two heteroatoms are known, and no Rh-catalysed processes have been reported.…”

Catalytic Asymmetric Synthesis of Geminal-Dicarboxylates

“…19,20,23,24 A variety of rhodium-catalysed asymmetric allylation-type processes, including allylic substitutions, with oxygen, nitrogen and carbon nucleophiles have been reported to form allylic alcohols, amines, and tertiary or quaternary carbon stereogenic centers. [30][31][32][33][34][35][36][37][38][39] Carboxylic acids may be used as nucleophiles, not only in rhodium-catalysed asymmetric reactions, 40 but also in processes catalysed by iridium, 41 palladium, 42,43 and ruthenium. 44 However, only limited examples of metal-catalysed asymmetric additions to make stereogenic centres bearing two heteroatoms are known, and no Rhcatalysed processes have been reported.…”