The synthesis of cyclic, chiral α-trifluoromethylated N,O-acetals having a protected cis-diol moiety has been readily achieved in two steps from
a known bis-Weinreb amide derived from l-tartaric acid. The
reaction of O-acetyl analogues of these N,O-acetals with triflic acid in 1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP) at 0 °C generated in situ the corresponding
electrophilic α-trifluoromethyl N-acyliminium
ions that undergo Pictet-Spengler-type cyclizations. After only 10
min of reaction, the original enantiopure aza-tricyclic scaffolds
bearing a trifluoromethyl substituent at the bridgehead position were
obtained with diastereoselectivities ranging from 75:25 to 97:3.
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