GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 131

N

N N

(Ph 3 P)AuCl (5 mol%)
AgOTf (5 mol%)
CH 2 Cl 2 , rt, 16 h
92%

steps

H

O

Et

Et

N
H

Et MeO 2 C

AuL

CO 2 Me

139 140 (dr = 97:3) (-)-Rhazinilam 141

SCHEME 4.40

An exemple of an allene-ene cycloisomerization was reported by Nelson and
coworkers in their total synthesis of (

)-rhazilinam 141 (Scheme 4.40) [38]. Hence,

treatment of the trisubstituted allene with 5mol% of the gold complex (Ph 3 P)

AuOTf induced a stereoselective 6- exo addition of the pyrrole nucleus on the allene
moiety. The resulting bicyclic compound

139

, which could be isolated in high yield
and purity, possessed two key architectural features of the targeted natural product:
the tetrahydroindolizidine ring system and the adjacent quaternary asymmetric
center. Notably, silver salts were completely ineffective for this transformation,
while (CH 3 CN) 2 PdCl 2 (30mol%) provided

140

as a 2:1 mixture of isomers.
Another type of cycloisomerization involving an alkyne and a nucleophilic
indole partner was described by Echavarren and coworkers in an approach to the
synthesis of the tetracyclic core of the lundurines (Scheme 4.41) [39]. The synthetic
studies carried out on model substrate

140

142

showed that the eight-membered ring of

the lundurine alkaloid could be formed by an 8- endo gold-catalyzed addition

of the indole moiety on the terminal alkyne.
Other types of nitrogen-containing heterocycles frequently found in the struc-
ture of natural products could be accessed through a gold-catalyzed reaction. Padwa
and coworkers, for instance, devised a new synthetic approach to b -carbolines
featuring a cycloisomerization of a tertiary indole-2-carboxamide (Scheme 4.42) [40].
Upon treatment with AuCl 3 (5mol%), substrate

145

146 underwent a 6- exo - dig cycli-

zation that afforded b -carbolinone in good yield. Subsequent removal of the tosyl

protecting group followed by treatment with POCl 3 furnished chloro- b -carboline

147

.
This method could be applied to the total synthesis of various natural products

148

O O O

AuCl 3 (5 mol%)
CH 2 Cl 2 , rt, 24 h
55%

N N N

H H H

Cl

143 144

142

( 143 : 144 = 95:5)

MeO

O

N

N

MeO 2 C

Lundurine A 145

SCHEME 4.41 Echavarren and coworkers' approach to the synthesis of the tetracyclic core

of lundurines.