GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 141

n

R = H

- [A u ]

HO

n
O

H

[Au]

[Au] n n n

206

RO

RO RO

-

[Au] [Au]

[Au]

n n

- [A u ]

204 205 n = 1, 2

O

-

[Au]

O R ′ O

R = COR ′

R ′

207

O

SCHEME 4.60

the propargylic position can lead to the formation of a cyclopropyl gold carbene
intermediate , following the mechanism shown in Scheme 4.60. A final 1,2-

hydride shift or 1,2-acyloxy shift produces the bicyclic compounds

205

206 or 207 with

regeneration of the gold catalyst.
This principle of reactivity was used by Furstner et al. and Fehr et al. to
synthesize a series of terpenoids such as sesquicarene

208

[57], sesquithujene

209 210

[59] that possess a bicyclo[3.1.0]hexane or a bicyclo
[4.1.0]heptane substructure (Scheme 4.61).
By treatment with an electrophilic gold species, a propargylic ester

[58], and cubebol

can also
undergo an initial 3,3-rearrangement that produces an intermediate acyloxyallene 212
(Scheme 4.62). The latter can then undergo a gold-catalyzed addition of a carbon
nucleophile [60]. This principle was used by Malacria and coworkers in their total
synthesis of the linear triquinane capnellene

211

216 (Scheme 4.62) [61]. Hence, treatment

of dienyne 213 with 2mol% of the gold complex [(JohnPhos)Au(CH 3 CN)]SbF 6

H H

OAc

1. AuCl 3 (5 mol%)
(CH 2 Cl) 2 , rt, 4 h
2. K 2 CO 3 , MeOH
74%

steps

H H

O

Sesquicarene 208

1. AuCl 3 (pyridine) (10 mol%)
CH 2 Cl 2 , rt, 4 h (76%)
2. LiOH, THF/H 2 O (89%)

O

steps

OAc

Sesquithujene 209

(Ph 3 P)AuCl (2 mol%)
AgSbF 6 (2 mol%)
CH 2 Cl 2 , rt, 0.66 h
65%

OPiv

2 steps

OH

OPiv

(dr = 88:12) (dr = 47:53) Cubebol 210

SCHEME 4.61 Synthesis of sesquicarene, sesquithujene, and cubebol by Furstner et al. and

Fehr et al.