A study of oligoprenyl coupling reactions with allylic stannanes

Article abstract of DOI:10.1021/ol026568p

(matrix presented) AII-E or E,Z,E-oligoprenols may be synthesized from allylic stannanes by reaction with prenyl aldehydes.

Full text of DOI:10.1021/ol026568p

ORGANIC
LETTERS
2002
Vol. 4, No. 20
3463-3464
A Study of Oligoprenyl Coupling
Reactions with Allylic Stannanes
Branko Radetich and E. J. Corey*
Department of Chemistry and Chemical Biology, HarVard UniVersity,
12 Oxford Street, Cambridge, Massachusetts 02138
corey@chemistry.harVard.edu
Received July 19, 2002
ABSTRACT
All-E or E,Z,E-oligoprenols may be synthesized from allylic stannanes by reaction with prenyl aldehydes.
We recently reported a strategically powerful method for the
stereoselective synthesis of all-E oligoprenols by the coupling
of two smaller oligoprenol fragments, as outlined in Scheme
1 (TBS ) tert-butyldimethylsilyl) for the all-E pentaprenol
obtained with allylic stannanes contrasted sharply with the
allylic silane couplings exemplified by 1 + 2 f 3.
The synthesis of the allylic stannane 7 from the corre-
sponding primary mesylate 6 proved to be surprisingly
challenging. The use of trimethylstannyllithium alone or in
combination with various metal additives invariably led either
to the primary allylic stannane 8 or to mixtures of 7 and 8.
Although the most promising results were obtained with Cu-
Scheme 1. Oligoprenyl Coupling
(I) additives, the ratio of 7 to 8 varied widely depending on
the additional ligands attached to copper in mixtures of CuI
or CuBr‚SMe2 with Me3SnLi2 and a third component in THF
as solvent. Thus, ratios of 7 to 8 as a function of additive
ligand were observed as follows: 2-thienyllithium, 1.2:1;
triphenylphosphine, 1.5:1; 1,2,4-triazolyllithium, 4:1. The
case (5).1 In connection with this work we have also studied
a parallel approach using organotin intermediates rather than
organosilanes such as 1. As described herein, the results
(2) (a) Still, W. C. J. Am. Chem. Soc. 1977, 99, 4836. (b) Still, W. C.;
Mitra, A. Tetrahedron Lett. 1978, 2659.
(1) Radetich, B.; Corey, E. J. J. Am. Chem. Soc. 2002, 124, 2430.
10.1021/ol026568p CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/30/2002

most selective reagent found was prepared from Me3SnLi,
CuI, and P(OMe)3, which gave in 75% yield a mixture of 7
and 8 in a ratio of 9 to 1. This proved to be satisfactory for
subsequent coupling reactions, since the minor primary allylic
stannane 8 is much less reactive than the secondary isomer
7.
Scheme 2
The secondary allylic stannane 7 underwent a clean
thermal metallo-ene coupling reaction with a series of
aldehydes to give in each case the Z-coupling product 9, as
summarized in Table 1. The reaction velocities for this series
Table 1. Z-Selective Thermal Metallo-Ene Coupling of Allylic
Stannane with Aldehydes
produce the all-E coupling product 12, in actuality it was
complicated by the concomitant formation of the alternative
primary-secondary coupling product 13. The ratio of 12 to
13 varied widely with Lewis acid, solvent, and temperature,
as can be seen from the following data for the ratio 12:13 as
a function of reaction conditions: 3:2 (BF3‚Et2O, CH2Cl2,
-78 °C); 1:4 (MeAlCl2, CH2Cl2, -78 °C); 3:2 (BF3 gas,
toluene, -78 °C; 1:4 (B(C6F5)3, toluene, -78 °C); 7:3 (BF3‚
Et2O, toluene, -78 °C). The best conditions found for the
preparation of 12 were 0.3 M 7, geranial, and BF3‚Et2O in
toluene at -78 °C, which led to 12 in 55% isolated yield
after silica gel chromatography. The synthesis of all-E
geranylgeraniol (15) from 12 was carried out via the
triisopropylsilyl (TIPS) ether 14 as outlined in Scheme 3.
entrya
R′
conditions
neat, 23 °, 24 h
neat, 60 °C, 24 h
neat, 70 °C, 24 h
0.9 M CH2Cl2, 60 °C, 24 h
neat, 90 °C, 48 h
yield
1
2
3
4
5
CCl3
Ph
Cy
75%
85%
45%
69%
63%
p-NO2C6H4
E-geranyl
a Entry 5, R ) TBS, otherwise R ) TBDPS.
paralleled the electrophilicity of the aldehyde component,
as expected. The Z-geometry of the newly created olefinic
linkage in the products shown in Table 1 was clear from 1H
NMR NOE data including NOEs of ca. 12% between the
olefinic CH3 and H on the new double bond. E,Z,E,-
Geranylgeraniol (10) was readily synthesized from 9, R′ )
E-geranyl, by the selective deoxygenation protocol sum-
marized in Scheme 3 for 12 f 15.1 The synthesis of 10
Scheme 3. Synthesis of All-E-Geranylgeraniol from Stannane
7
demonstrates an advantageous route to such mixed E/Z
oligoprenol systems, several of which occur naturally in
dolichol and bacterial and plant oligoprenols.3
The selective generation of Z-olefinic geometry in the
products 9 is readily explained by comparison of the chairlike
transition states 11a (which would lead to the observed Z
olefin) and 11b (which would produce the disfavored E
product). As indicated in Scheme 2, 11b is destabilized
relative to 11a by steric repulsion between one of the methyls
attached to Sn and the vicinal methylene group.
Acknowledgment. We are grateful to Pfizer Inc. for
generous research support.
Supporting Information Available: Experimental pro-
cedures for the compounds described, along with NMR, IR,
and mass spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
Although the reaction of the allylic stannane 7 with
E-geranial in the presence of Lewis acids was expected to
(3) (a) Hemming, F. W. In Biochemistry of Lipids; Goodwin, T. W.,
Ed.; Butterworths: London, 1974; p. 39. (b) Poulter, C. D.; Rilling, H. D.
Acc. Chem. Res. 1978, 11, 307.
OL026568P
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Org. Lett., Vol. 4, No. 20, 2002