(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.
