GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 126

OAc OAc OAc

(Ph 3 P)AuBF 4
(5 mol%)
CH 2 Cl 2 , rt, 4 h
92%

LiAlH 4
THF
91%

NH N N

O O

94 95

Supinidine

96

OH

HO

H

trans
isomer

N

OAc OAc 79%

AcO AcO

(Ph 3 P)AuBF 4
(5 mol%)
CH 2 Cl 2 , rt, 4 h
84%

H H

Retronecine

99

LiAlH 4

NH N

OH

THF HO

cis
isomer

H

O O

97 98

56% N

( cis / trans = 17:83)

Heliotridine

100

SCHEME 4.29 Synthesis of supinidine, retronecine, and heliotridine by Hiemstra and

coworkers.

excellent 99% yield with a complete control of the stereoselectivity. A sequence
of four additional steps was then required to convert

102 into Pyne's intermediate

103

. The latter could be used as a substrate to achieve the total synthesis of
swainsonine [29].

Bates and Lu have also taken advantage of the possibility to add a nitrogen
nucleophile on an allene to stereoselectively synthesize the bicyclic carbamate 107 ,
an intermediate in the total

104

synthesis of the porantheridine alkaloid 108

(Scheme 4.31) [30]. The allene could then be transformed in moderate yield

and diastereoselectivity into vinylisoxazolidine

105

in the presence of 5 mol% of
AuCl 3 , while a subsequent nine-step sequence afforded the bicyclic lactam

106

107 , the

precursor of porantheridine .

Finally, an example of a gold-catalyzed intramolecular addition of a nitrogen
nucleophile on an alkene was reported by Chan and coworkers in their concise total
synthesis of angustureine

108

109
with a combination of AuCl (5mol%) and AgOTf (15 mol%) in refluxing toluene
furnished the vinyldihydroquinoline

111 (Scheme 4.32) [31]. Hence, treatment of dienol

in 69% yield. The new C-N bond was
proposed to be formed by the nucleophilic addition of the tosylamide group on a
stabilized carbocation generated by the action of the electrophilic gold catalyst on the
dienol system present in

110

. The hydrogenation of the residual unsaturations,
followed by the removal of the tosyl group and the methylation of the nitrogen
atom, finally furnished the desired alkaloid.

109

OTBS TBSO HO

OTBS

AuCl 3
(5 mol%)
CH 2 Cl 2 /CH 3 CN
CaCO 3 , rt, 1 h
99%

OH

H H

4 steps

[29]

OH

NHBoc NBoc N N

101 102

Pyne's
intermediate 103

Swainsonine 104

SCHEME 4.30 Bates and Dewey's formal synthesis of swainsonine.