Asymmetric propionate aldol reactions of a chiral lithium enolate accessible from direct enolization with n-butyllithium

The presented lithium enolate-based methodology is suitable for access to propionate syn-aldol motifs with high levels of stereocontrol. The reactive lithium enolate species is generated by direct treatment of a camphor-based chiral ethyl ketone with butyllithium, and is subsequently submitted to al...

Descripción completa

Detalles Bibliográficos
Autores: Palomo, Claudio, Oiarbide, Mikel, Gómez Bengoa, Enrique, Mielgo, Antonia, González Rego, María Concepción, García Castillo, Jesús María, González Guerrero, Alberto, Odriozola Ibarguren, José Manuel, Bañuelos Villaverde, Patricia, Linden, Anthony
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2005
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/23502
Acceso en línea:https://hdl.handle.net/2454/23502
Access Level:acceso abierto
Palabra clave:Lithium enolates
Aldol reaction
Asymmetric synthesis
Hapalosin
Butyllithium
Descripción
Sumario:The presented lithium enolate-based methodology is suitable for access to propionate syn-aldol motifs with high levels of stereocontrol. The reactive lithium enolate species is generated by direct treatment of a camphor-based chiral ethyl ketone with butyllithium, and is subsequently submitted to aldolization with a broad variety of aldehydes. The product aldols are obtained in uniformly high yields and high d.r. values (ranging from 91:9 to >98:2) irrespective of the aliphatic (both linear and branched chain), α,β-unsaturated, aromatic, or hetero-aromatic nature of the aldehyde employed. The crystallinity of most of the obtained adducts offers an easy access to almost 100% isomerically pure products upon a single recrystallisation. The auxiliary (1R)- (+)-camphor can be removed easily from the adducts for reuse, thereby producing the corresponding syn propionate aldols. This technology is implemented in the synthesis of a key subunit of the multi-drug resistance reversing agent hapalosin.