Iridium-Catalyzed Intramolecular Asymmetric Allylic Etherification of Pyrimidinemethanols: Enantioselective Construction of Multifunctionalized Pyrimidine-Fused Oxazepines

An iridium-catalyzed intramolecularasymmetric allylic etherificationof pyrimidinemethanols is described. In the presence of chiral-bridgedbiphenyl phosphoramidite ligand L3 and triethylborane,this process provided a class of novel pyrimidine-fused oxazepanesin up to 99% yield with 99.5% enantiomeric excess. The work addressesthe challenge of insufficient nucleophilicity of aliphatic alcoholsfor allyl substitution and indicates the vital value of chiral-bridgedbiphenyl phosphoramidites. Various multifunctionalized transformationsof the products further demonstrate the robust synthetic utility ofthis methodology.

Automated summary

An iridium-catalyzed intramolecular asymmetric allylic etherification of pyrimidine methanols using chiral-bridged biphenyl phosphoramidite ligand L3 and triethylborane resulted in the synthesis of a class of novel pyrimidine-fused oxazepanes with up to 99% yield and 99.5% enantiomeric excess. This work addresses the challenge of insufficient nucleophilicity of aliphatic alcohols and demonstrates the vital value of chiral-bridged biphenyl phosphoramidites. The multifunctional transformations of the products further showcase the robust synthetic utility of this methodology.