AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOID SYNTHESIS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 464

EtS

EtS

EtS

TMS O

O

Tf 2 O
TBAT

O

N

N

N Me

Me

71%

OTf

OTf

O O

OO

Me

O

OO

301 302 303

O

O

Me

O

OMe
Me

N

Me

O

Stemofoline

SCHEME 13.57

In an approach to the homoerythrina alkaloids, the Pearson group modified the
three-component reaction employing a -stannyl amine 190a (Scheme 13.39) [102].
Accordingly, reaction of ketone 296 , which possesses a vinyl sulfone dipolarophile,
and 190a in toluene at 85 C furnished 297 as a single diastereomer in 56% yield
(Scheme 13.56). Reductive cleavage of the sulfone moiety using LiEt 3 BH and
catalytic amounts of PdCl 2 (dppp) provided 298 in 84% yield. The position of the
carbon-carbon double bond in 298 corresponds to that found in homoerythratine.
Alternatively, ketone 299 , which possesses a vinyl sulfoxide, reacted with 190a under
similar conditions to give 300 in 56% yield. The diene portion of 300 is the same as
found in 3- epi -schelhammeridine.
Gin and coworkers reported an interesting variation on the Vedejs method for
ylide formation (Scheme 13.35) [103]. In an approach to the stemofoline members of
the stemona alkaloids, pyrrolidine 301 was treated with triflic anhydride and tetra-
butylammonium triphenyldifluorosilicate (TBAT) to generate azomethine ylide 302
(Scheme 13.57). Cycloaddition of the dipole across the pendant vinyl sulfide
furnished 303 in 71% yield.

13.2.7. Other Strategies
Although several of the condensation reactions used to generate azomethine ylides
involve a prototropic shift, examples where the imine structure is elaborated before
the prototropic shift occurs are much less common. The Overman group employed
this kind of delayed prototropic shift while exploring synthetic routes toward complex
guanidinium alkaloids [104]. In this study, cyclization precursors 305a and 305b were
prepared by the alkylation of ( E )-methyl 2-(benzylideneamino)acetate with 304a and
304b (Scheme 13.58). Heating 305a and 305b in xylene at reflux produced 306
and 306b as single diastereomers in 51% and 86% yields, respectively. In addition,
307 furnished 308 in 48% yield when a xylene solution was heated to reflux in the
presence of NH 4 Cl.