REARRANGEMENTS IN NATURAL PRODUCT SYNTHESIS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 253

E Z

LHMDS, HMPA
-78°C to reflux

O O O

TBSO

O

O O

TBSCl

O

OLi

TBDPSO

TBDPSO TBDPSO

MOMO OMe

MOMO OMe MOMO OMe

CO 2 H O O

LiAlH 4 , Et 2 O, 0°C

OH

HO

O

O

HO

OMe OMe

TBDPSO TBDPSO

MOMO MOMO HO

O

84% (for two steps)
(dr = 4:1)

(-)-Kendomycin

SCHEME 8.18 Total synthesis of ( )-kendomycin.

8.4. THE OVERMAN REARRANGEMENT

The Overman rearrangement is a 1,3-transposition of an alcohol or an amine via a
[3,3]-sigmatropic rearrangement of an allylic trichloacetimidate [6,114]. The most
important aspects of this rearrangement are that (a) allylic trichloroacetimidates are
easily accessible by treating allylic alcohols with trichloroacetonitrile in the presence
of a catalytic amount of base, (b) the rearrangement occurs by simple heating of the
crude trichloroacetimidate in xylene at temperatures ranging from 30 C to 140 C,
(c) the allylic amines are isolated in high yield after basic hydrolysis, (d) the [3,3]-
sigmatropic rearrangement is regiospecific and highly stereoselective in the case of
secondary allylic alcohols as only ( E )-alkenes are formed, and (e) the catalyst, usually
mercuric(II) salts (10-20 mol%), is easily removed by chromatography or complex-
ation with pyridine or PPh 3 . Concerning the mechanism, the Overman rearrangement
is a irreversible, suprafacial, concerted, and nonsynchronous [3,3]-sigmatropic
transposition.
Applications of the Overman rearrangement to the synthesis of natural products
include the synthesis of lincosamine and 7- epi -lincosamine [115], polyoxamic
acid [116], polyoxin C [117], blastidic acid and cytosinine, two components of the
antibiotic blasticidin S [118], sphingofungin E [119], racemic pancratistatin [120],
( )-dibromophakellin [123].

Compound A-315675, which is a synthetic antiinfluenza agent, has been
synthesized in enantiomerically pure form starting from diisopropyl D -tartrate via
two consecutive Overman rearrangements (Scheme 8.19) [124].
In their continued efforts to synthesize tetrodotoxin, the toxic principle of puffer
fish poisoning, Isobe and coworkers [125] recently reported a scalable synthesis of a
new dihydroxylated intermediate bearing two hydroxyl groups at C8 and C11,
featuring an Overman rearrangement as a key step [126] (Scheme 8.20).
The selective inhibition of glycogen synthase-3 b as well as other diverse
biological activities shown by agelastatin A, a natural compound isolated from the
axinellid sponge Agelas dendromorpha , has attracted the interest of a number of
groups around the world. Wardrop and Dickson [127] and Chida and coworkers [128]

)-cryptoleurine [121], mycestericin A [122], and ( þ