Reaction of chiral diamine 3.11a with succindialdehyde (3.19, obtained by

treatment of 2,5-dimethoxytetrahydrofuran with 0.1 M HC1) and benzotriazole in CH2C12

at room temperature for 24 h readily afforded Bt intermediate 3.22 as a single enantiomer

in 81% yield (Scheme 3-6). The stereochemistry of 3.22 was determined by NOE NMR

experiments. H NMR spectra of 3.22 show that H(3), H(7a) and H(5) appear at 3.7 ppm

multipleet, 5.1 ppm (doublet-doublet) and 6.0 ppm (triplet), respectively. A significant

positive NOE effect was observed between H(3) and H(5), and no NOE effect was

observed between H(7a) with either H(3) or H(5). Thus, NOE analysis demonstrates that

H(3) and H(5) in 3.22 are in a cis-orientation whereas H(3) and H(7a) are in trans-

orientation.

 Treatment of 3.22 with 2 equiv of AlC13 did not afford the desired 3.23, but gave a

decomposed mixture possibly due to the labile NCHN moiety in the presence of a Lewis

acid.

 3.3 Conclusion

 In summary, starting from easily available N-Boc-a-amino-acids, we have

developed an efficient method for the preparation of novel enantiopure 1,2,3,5,10,10a-

hexahydroimidazo[1,5-b]isoquinolines 3.1a-c, 2,3,10,1 a-tetrahydroimidazo[ 1,5-

b]isoquinolin-l(5H)-ones 3.15a-c and 3.18a-c via Lewis acid promoted iminium cation

intramolecular cyclizations.

 3.4 Experimental Section

 Column chromatography was performed on silica gel (200-425 mesh). All of

reactions were carried out under nitrogen.