Enantioselective Allylation of Thiophene-2-carbaldehyde: Formal Total Synthesis of Duloxetine

Abstrakt

The enantioselective allylation of thiophene-2-carbaldehyde with allyltrichlorosilane under Lewis base catalysis has been studied. The use of catalytic amount (1mol%) of chiral bipyridine N,N-dioxides provided the corresponding 1-(thiophen-2-yl)-but-3-en-1-ol with asymmetric induction reaching 97% ee.

The prepared chiral (S)-1-(thiophen-2-yl)-but-3-en-1-ol was used as the crucial chiral building block in a formal total synthesis of duloxetine.

Klíčová slova

• aldehydes
• allylation
• Lewis bases
• organocatalysis
• synthetic methods