A. W. Kruger, A. I. Meyers / Tetrahedron Letters 42 (2001) 4301–4304
4303
1. Pd(CH3CN)2Cl2,
THF, 54%
Bu3Sn
NHBoc
H
NHBoc
H
PhSO2Na,
DMF, 90%
OH
25
2. NBS, PPh3,
CH2Cl2, 90%
Br
26, >10:1 (Z:E)
PhO2S
27
Scheme 5.
CO2CH3
R1
R2
I
R
I
28, R = OH, R1 = OH
29, R = OTBS, R1 = OH
30, R = OTBS, R1 = CHO
31, R = OTBS, R1 = CH=CHI (Z)
32, R2 = CO2Me
33, R2 = CHO
(16:1 Z:E)
34, 16:1 Z:E
Scheme 6.
Hydrolysis (LiOH) of the ester of 34 led to fragment 4
The synthesis of fragment 3 was initiated by allylation
of imine 21 at −78°C using (+)-(ipc)2B-allyl (Scheme
4).11 Protection of the amine as the Troc-carbamate,
followed by ozonolysis, produced the aldehyde 22 in
92% ee and 75% yield. Wittig homologation12 gave 24
in greater than >10:1 (Z:E) ratio, but in low chemical
yield (ca. 40%). However, utilization of the correspond-
ing Boc-derivative 2313 increased the chemical yield of
vinyl iodide 25 to 73%, with a >10:1 ratio of Z:E
olefins.
required for the route to viridenomycin.
In summary, the three key fragments (2–4) required for
the total synthesis of 1 have been prepared. Unfortu-
nately, the Julia coupling2 required to join fragments 2
and 4 failed to produce consistent alkene formation in
a closely related model system and thus discouraged
further efforts dedicated to this route. An alternate
plan, with new synthetic strategy was next embarked
on.17
Palladium-catalyzed coupling of the vinyl iodide 25
with the known vinylstannane14 gave the (Z,E)-dienyl-
alcohol, which was directly converted into the some-
what labile bromide 26 (Scheme 5). Displacement of the
bromide with sodium phenyl sulfinate in DMF pro-
duced the allylic sulfone 27, corresponding to the requi-
site fragment 3.
Acknowledgements
The authors are grateful to the National Institutes of
Health, Merck Sharpe and Dohme, and SmithKline
Beecham for financial support of this study.
The (Z,Z)-dienyl iodide 4 (Scheme 1) was initially
found to be difficult to reach in greater than ꢀ8:1
(Z:E) stereoselectivity. An early approach utilized
mono-silylation of the readily available cis-butene-diol
28 to the t-butyldimethylsilylether 29 and subsequent
oxidation of the remaining allylic alcohol with Dess–
Martin periodinane10 to afford enal 30 (Scheme 6). The
latter was thermally unstable to E/Z isomerization and
had to be elaborated immediately. Unfortunately,
olefination12 produced diene 31 in only a modest 7.5:1
ratio of (Z) to (E) isomers at the newly formed double
bond. Unable to separate the isomers, this route was
abandoned in favor of the following. Methyl (Z)-iodo-
acrylate 32 (>99:1, Z/E)15 was reduced using DIBALH
to afford the (Z)-iodo-acrolein 33, which now exhibited
less erosion of the alkene stereochemistry (16:1, Z/E).15
References
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Application of
Wadsworth–Emmons reaction furnished the iodo-
dienoate 34 as an acceptable 16:1 mixture of isomers.
a
modification16 of the Horner–