GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 144

R

O

R -[Au] R

R

[Au ]

X X X X

R

O

X

O O

O

[Au]

[Au]

221 222

X = (CR ′ ), NR ′ , O

2

R X R X

HO

OH

223 224

BrMg
1. , TH F
2. SiO 2 , CH 2 Cl 2
3. LAH, Et 2 O

AuCl 3 (2.9 mol% )
CH 3 CN, rt, 2 h
75%

O

O

O OH

OH OH

225

Jungianol 226 epi - 226

(20%) (65%)

SCHEME 4.65 Synthesis of jungianol by Hashmi and coworkers.

homogeneous gold catalysis (Scheme 4.65) [66]. It is also another example of
structural rearrangement. The furan ring of the substrate is cleaved during the course
of the reaction to produce an intermediate gold carbene . The latter is then

intercepted by the carbonyl moiety to afford the arene oxide/oxepin system, which
subsequently aromatized into furans

222

223 224

and , depending on the nature of the

substituents present on the furan ring of . This transformation was applied to the

total synthesis of the sesquiterpene jungianol 226 by treatment of furan-yne 225 with
2.9 mol% of AuCl 3 in CH 3 CN [67].

221

4.4.2.2. Keto-Yne Reactions In addition to enyne cycloisomerizations in
which an alkyne reacts with an alkene nucleophile, gold-activated alkynes can
also interact with a keto functionality such as an aldehyde or a ketone to furnish
an oxocarbenium intermediate of type

227 . The latter can then be engaged in a [4 þ 2]-

cycloaddition reaction or in a 1,3-dipolar cycloaddition (via resonance structure 228)

with an alkyne or an alkene partner, respectively (Scheme 4.66).
The total synthesis of the antibiotic natural product ( þ )-rubiginone B2 233

by Asao and coworkers features an example of such a [4 þ 2]-cycloaddition

(Scheme 4.66) [68]. The treatment of diyne with 2 mol% of AuCl 3 allowed the

formation of the isobenzopyrylium cationic species

229

, which subsequently reacted
with the pendant alkyne to produce the bridged cationic intermediate

230

231 . A final

rearrangement furnished the benzannulated product 232 , a direct precursor of

( and

ethyl vinyl ether was described by Zhang and coworkers for the formation of the
functionalized bicyclo[3.2.0]heptene

þ )-rubiginone B2 233 . A 1,3-dipolar cycloaddition between 1,3-ynone 234

236 (Scheme 4.66) [69]. From the initially

formed oxocarbenium , a 1,3-dipolar cycloaddition followed by a cascade of

rearrangements occurred to finally produce compound

235

236

whose structure is found in

repraesentin F 237 .