DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 290

O

OBn

t- BuLi, Et 2 O

160

OLi OTMS

S S S

Li

S S

TMS

S S

Li

S

-78°C to 45°C

12-crown-4
THF, -20°C

TMS R R

TMS

158 159 161 162

HMPA, THF
-78°C to rt
3 h

O O

163

Steps

O O O O O O TBSO OH HO OTBS

S S S S

HO BnO OBn

TBSO

164

(+) - 165

Schreiber
and coworkers

OH OH OH OH OH OH

HO O R

HO O

Mycotacin A (R = H, 166 )
Mycotacin B (R = Me, 167 )

SCHEME 9.28 Synthesis of mycotacins A 166 and B 167 by Smith and coworkers.

164 containing four stereogenic centers could be obtained in a highly efficient way

and with excellent stereoselectivity [67]. Following treatment of the starting material
158 with t -BuLi, lithiated silyldithiane 159 is formed, which reacts with the

enantiopure epoxide 160 to give 161 ; it follows a Brook rearrangement to give

lithium dithioacetal 162 . Treating this compound with an equivalent of bis-epoxide

163 affords ( þ )-diol 164 in 56% yield. This dithioacetal can then be converted to

triacetonide 165 , which is required in the synthesis of (+)-mycotacin A 166 by

Schreiber and coworkers (Scheme 9.28).
In a similar set of reactions, the group of Smith has also used a combination of
an epoxide such as

169 and an aziridine 170 to generate a useful intermediate in the

synthesis of indolizidine 223AB alkaloid ( 172 ) (Scheme 9.29) [68]. Moreover, by this

way the synthesis of alkaloid ( ) has also been accomplished [69].

Both these natural products were isolated from the frog species neotropical dart-
poison frogs belonging to the genus Dendrobates . In many cases, these indolizidine-
based compounds show interesting biological activity.
The antifeedent properties of the natural product ( )-tanabalin ( 179 ) elicited
interest in the synthesis of this trans -decalin. A highly efficient large-scale production
of this compound that shows potent activity against pink bollworm ( Pectinophora
gossypiella ), a severe cotton pest, would no doubt help in farming activities. The
group of Watanabe has devised such an efficient synthesis by developing a short
access to the trans -decalin core beginning with the enantiopure iodoalkane

)-205B ( 173

174

(Scheme 9.30) [70]. Alkylation of the enolate of keto ester 175 with acetal 174

initially forms intermediate 176 that then undergoes a Michael addition to cyclohex-

ene 177 containing four contiguous stereocenters. A second cyclization of