Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

APPLICATIONS OF NITRILE OXIDES 97
Three novel stereo- and regioselective schemes for the total synthesis of
( + )-brefeldin A 440 have been accomplished. Each of them exploit intermolecular
nitrile oxide cycloaddition for constructing the open chain and introducing
substituents, but differ in subsequent stages. The Þrst (480) and the second (481)
use intramolecular cycloaddition for the macrocycle closure. However, in the second
scheme INOC is followed by C=C bond cis-trans-isomerization. In the third
scheme (481) intermolecular cycloaddition is followed by ring closing metathesis
as the key step.
HO
H
H
OH
440
A stereoselective total synthesis of erythronolide A, using two Mg II -mediated
cycloadditions of nitrile oxides has been described. Of broader signiÞcance, the
strategy not only facilitates the synthesis of speciÞc polyketide targets (i.e., natural
products) but also opens up new possibilities for the preparation of nonnatural
analogs (482).
The uniÞed highly convergent total and formal syntheses of ( + )-macrosphelides
B (441; X= O) and A (441; X= α-OH, β-H), respectively, have been
described (483). Key features of the syntheses include the concise synthesis of
the optically active δ-hydroxy-γ-keto α,β-unsaturated acid fragment 442 via the
direct addition of a trans-vinylogous ester anion equivalent to a readily available
Weinreb amide, and the facile construction of the 16-membered macrolide core
of the macrosphelide series via an INOC.
X
Me
O
O
O
Me
OH
O
O
Me
O Me
MeO Me
O O MeO
O O
441 442
O O
The stereoselective formation of the C ring of paclitaxel 443 has been accomplished
by the nitrile oxide [3 + 2] cycloaddition of intermediate 444 to the
preformed A ring (484).
OH