posted on 2024-03-09, 14:11authored byRachel H. Munday
A new
route to a key ether intermediate in the synthesis of Lanabecestat
is described. A directed hydrogenation approach was investigated as
an alternative to the previous route, which used a borane reduction
of a diketone giving a selectivity of 80:20. Directed hydrogenation
of an enol ether intermediate gave a selectivity of >99:1 for the
desired ether but the enol ether was problematic to synthesize and
isolate. The ketal was investigated as an alternative substrate and
found to give the same high selectivity, avoiding the issues of enol
ether synthesis. Mechanistic studies indicate that this reaction proceeds
via the enol ether.