Scheme 1
Figure 1.
intermediate.16 Recently, it has also been rendered intra-
molecular17 (7 f 8). We report here a stereoselective total
synthesis of (()-tangutorine featuring this intramolecular
formal aza-[3 + 3] cycloaddition strategy.
indoloquinolizidine alkaloids.12-15 Annulation of chiral vi-
nylogous amides 4 with R,â-unsaturated iminium salts 5
provides a highly stereoselective approach to dihydropy-
ridines 6a/b (Figure 1).12,13 This stepwise formal aza-[3 +
3] cycloaddition involves a tandem Knoevenagel condensa-
tion-stereoselective pericyclic ring-closure of an 1-azatriene
As outlined in Scheme 1, tangutorine (1) was envisioned
to arise from the pentacycle 9, which lacks only the C22
hydroxymethyl group. To construct pentacycle 9, the in-
tramolecular aza-[3 + 3] cycloaddition would be featured
using R,â-unsaturated iminium salt 10. The key R,â-
unsaturated aldehyde precursor for the iminium salt 10 could
be obtained from condensation of amino alcohol 11 with 1,3-
cyclohexanedione followed by oxidation of the allyl alcohol
moiety. Amino alcohol 11 would be prepared via a Heck
coupling of a suitably protected 2-halo-tryptamine 12, and
the ultimate starting point would be tryptamine 13. Thus,
another unique feature in the synthesis of monoterpenoid
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