Asymmetric Total Synthesis of Fasicularin by Chiral N-Alkoxyamide Strategy.

The asymmetric total synthesis of fasicularin is reported. The key to success is the use of a chiral N-alkoxyamide to control both reactivity and stereoselectivity. This functional group enables the aza-spirocyclization and the reductive Strecker reaction, which cannot be realized with an ordinary amide. In addition, use of the chiral alkoxy group establishes two consecutive stereocenters in the aza-spirocyclization through remote stereocontrol.

Crystal structure of (±)-(5SR,6SR)-6-ethenyl-1-[(RS)-1-phenyl-eth-oxy]-1-aza-spiro-[4.5]decan-2-one.

In the title compound, C19H25NO2, the pyrrolidine ring adopts an envelope form, with the spiro C atom as the flap, while the cyclo-hexane ring shows a chair form. A weak intra-molecular C-H⋯O inter-action supports the mol-ecular conformation, generating an S(6) ring motif. In the crystal, pairs of C-H⋯O inter-actions connect the mol-ecules into inversion dimers with an R 2 (2)(16) ring motif. The dimers are linked by a second pair of C-H⋯O inter-actions, enclosing an R 4 (2)(12) ring motif, into a tape structure along the b axis.