GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 138

-

[Au]

[Au]

[Au]

Au

R

R = H, SiR' 3

O

O

OR

OR

H

181 182 183

LAu (Ph 3 P)AuCl

(3 mol%)
AgBF 4 (3 mol% )

LAu

H

H

H

H

CH 2 Cl 2 , rt, 2 h

OH

87% O

Ventricosene 184

OH

LAu

(JohnPhos)AuCl
(10 mol%)
AgSbF 6 (5 mol%)

O

OPh

H

OPh

NOH

O

OTBDPS

i -PrOH (1.1 equiv)
CH 2 Cl 2 , rt, 0.33 h

OTES

OTBDPS O

O

78%

(+)-Sieboldine A 185

SCHEME 4.55

4.4.1.3. Enyne Cyclizations with Ring Expansion or Fragmentation As
previously seen in the synthesis of indolizidine 167B (Section 4.3.2.1), gold-
catalyzed cycloisomerizations can lead in some cases to a profound skeletal
rearrangement of the substrates. The enyne cycloisomerizations employed in the
synthesis of the natural products ventricosene

, which
have been reported by Toste and coworkers [51] and Overman and coworkers [52],
respectively, are also typical examples of structural reorganization (Scheme 4.55).
Both syntheses feature the same kind of gold-catalyzed cycloisomerization as the
key step. The 6- exo - dig cyclization of a 1,6-enyne

184 and ( þ )-sieboldine 185

181

possessing a hydroxyl
functionality at the allylic position of the linker can lead to the formation of an
intermediate of type , which can then undergo a subsequent pinacol rearrangement

to furnish compound 183 .
Another different process of annulation/fragmentation sequence was recently
described by Solorio-Alvarado and Echavarren (Scheme 4.56) [53]. Upon treatment
with 5 mol% of the gold complex [(JohnPhos)Au(NCCH 3 )]SbF 6 , enyne

182

186 under-

went a 6- endo - dig cyclization to produce gold species 187 after a 1,2-hydride shift. A

retro-cyclopropanation proceeding via intermediate 188 then gave naphthalene 189

and gold carbene 190 . This transformation was applied to the synthesis of naphthol

191 , a known precursor of the cytotoxic alkaloid macarpine 192 .

4.4.1.4. Cascade Reactions with Formation of an Additional C-O or C-N
Bond In certain cases, the cycloisomerization of enynes can be interrupted by the
nucleophilic interception of a cationic intermediate species involved in the process.
Wang and coworkers took advantage of this possibility to synthesize the polycyclic