GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 125

4.3.1. Cyclizations Involving the Formation
of a New C-N Bond
4.3.1.1. FromAllenes and Alkenes By analogy with the formation of oxygen-
containing heterocycles (see Section 4.2.1.1), allenes and alkenes can be activated by
an electrophilic gold species toward the intramolecular addition of a nitrogen
nucleophile (generally an amide, a carbamate, or a sulfomanide) (Scheme 4.28).
The transformation can lead to the formation of various heterocycles depending both
on the length of the linker between the allene/alkene and the nitrogen nucleophile and
the exo or endo nature of the cyclization.
In the case of a - and b -allenamides, the gold-catalyzed transformation delivers,
respectively, 2,5-dihydropyrroles and 1,2,3,6-tretahydropyridines [24], while a -vinyl
pyrrolidines and piperidines are obtained from g - and d -allenamides [25]. Alkene
substrates react in a similar fashion to furnish pyrrolidine or piperidine derivatives by
a5-or6- exo cyclization of g - and d -alkeneamides [26].
Given the occurrence of nitrogen-containing heterocycles in the structure of
biologically active compounds, the gold-catalyzed transformations described previ-
ously have led to several applications in total synthesis. For instance, Hiemstra and
coworkers have reported that a Au(I)-catalyzed cyclization of substituted
a -allenylpyrrolidinones could be employed to synthesize the pyrrolizidine alkaloids
supinidine

96 99 100

, heliotridine , and retronecine (Scheme 4.29) [27]. Hence,

treatment of a -allenylpyrrolidinones

94 97

with (Ph 3 P)AuBF 4 (5 mol%) in
CH 2 Cl 2 for 4 h led to the isolation of the bicyclic lactams

and

95 98

in 92% and
84% yields, respectively. A subsequent one-pot reduction of the ester and lactam
functionalities furnishes the desired alkaloids in moderate to good yields.
An example of a stereoselective 6- exo gold-catalyzed cyclization of a carba-
mate onto an allene was described by Bates and Dewey in their formal synthesis of the
mannosidase inhibitor swainsonine

and

104 (Scheme 4.30) [28].

The d -aminoallene derivative 101 was converted to the corresponding N -Boc-

protected vinyl piperidine by treatment with 5 mol% of the Au(III) salt AuCl 3 .

Not only the reaction was rapid, but it also delivered the desired azacycle in an

102

n = 1,2 n = 3,4

Au(I) or Au(III) Au(I) or Au(III )

n

m

5- or 6 -endo 5- or 6 -exo

m

N N

HN

G

G G

m = 1 2,5-Dihydropyrrole
m = 2 1,2,3,6-Tetrahydropyridine

G = COR n = 1- 4
CO 2 R
SO 2 R

m = 1 Pyrrolidine
m = 2 Piperidine

Au(I) or Au(III )
5- or 6 -exo

n

N

m

HN

G

G

G = COR n = 1,2
CO 2 R
CONHR
SO 2 R

m = 1 Pyrrolidine
m = 2 Piperidine

SCHEME 4.28