Open Access
Asymmetric propionate aldol reactions of a chiral lithium enolate accessible from direct enolization with n-butyllithium
(ARKAT USA, Inc., 2005) 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; Química Aplicada; Kimika Aplikatua
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.

Odriozola Ibarguren, José Manuel

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