acetate and simultaneous hydrolysis of the homoallylic
acetate, as was reported in a related system (entry 7).12
Allylic tetrahydropyranyl (THP) ethers are commonly
used as a protecting group under basic conditions, but can
be regarded as a leaving group in the cross-coupling
reaction with organocopper reagents.13 The leaving group
ability of acetal protecting groups was also demonstrated
for 1-ethoxyethyl (EE) ethers in the Cu(I)-mediated cou-
pling reaction with Grignard reagents.14 We were very
happy to find that acetal protecting groups might also be
regarded as a good leaving group in the Pd-catalyzed
deoxygenation with Super hydride (LiBHEt3), and that it
was selective only for allylicalcohols. Diacetals9f(EE) and
9g (MOM) respectively produced the corresponding
monoacetal 1c (68% yield) and 1d (64% yield) by the
Pd-catalyzed deoxygenation with LiBHEt3 (entries 8ꢀ9).
Acetals from the homoallylic alcohols survived the above
deoxygenation condition. (þ)-S-Lavandulol (1e) was ob-
tained quantitatively after deprotection of monoacetal 1c
under catalytic p-TsOH in MeOH.
The generality and selectivity of this unprecedented
deoxygenation method for allylic alcohol was demon-
strated for various compounds (Table 3). The deoxygena-
tion proceeds at the EE-protected allylic alcohol through
the π-allyl palladium complex, in which hydride is deliv-
ered to the less-hindered site. The reduction is highly
regioselective if there is steric bias in the substituents of
the π-allyl complex. Either retention (entries 1ꢀ2, 6, and
9ꢀ11) or complete migration (5 and 7) of the car-
bonꢀcarbon double bond has occurred. A ∼1:1 mixture
of regioisomers was obtained when the size of the sub-
stituents was comparable (entries 4 and 8). The deoxygena-
tion is selective only for the EE ethers from allylic alcohols,
and those from benzylic alcohol and simple alcohol survive
the reaction condition (entries 5 and 8) as was demon-
strated in the lavandulol synthesis.
We were curious about any selectivity for desulfonation
over deoxygenation in the Pd-catalyzed reduction with
LiBHEt3, since the same reagents under milder condition
(25 °C instead of 70ꢀ80 °C) have been applied to the
desulfonation reaction in the sulfone-mediated chain-ex-
tension of terpenoids.15 Compound 27 was prepared by
EE-protection of the coupling product between geranyl
sulfone and (E)-3,7-dimethylocta-2,6-dienal, and was sub-
jected to the desulfonation condition (room temperature
for 6 h). Allylic alcohol 28 was exclusively obtained in 69%
yield after deprotection of the acetal group, which impli-
cated that sulfone is a better leaving group than EE-ether
(entry 9). Both desulfonation and deoxygenation are also
possible by sequential elimination at room temperature
and then at 70ꢀ80 °C (entry 10). Squalene (31) can be
prepared in 77% yield by this protocol from the EE ether
30 generated by the coupling between (2E,6E)-farnesyl
sulfone and (2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienal
(entry 11).
In summary, the stereocontrolled total synthesis of (þ)-
S-lavandulol has been completed in seven steps, 44%
overall yield from a readily available (ꢀ)-R-carvone. This
method highlights the oxidative ring-opening of the 1,2-
diol derived from the cyclic template and the deoxygena-
tion of the acetal-protected allylic alcohol, which is quite
general and selective even in the presence of benzylic or
other simple alcohols.
Acknowledgment. This work was supported by the
Korea Research Foundation (Grant KRF-2006-312-
C00580) and by Priority Research Centers Program (No.
2010-0028300) through the NRF of Korea funded by the
MEST. Special thanks go to Dr. Carsten Blettner at BASF
for generous donation of high-quality LiBHEt3 reagent.
(9) (a) Yeo, J. E.; Yang, X.; Kim, H. J.; Koo, S. Chem. Commun.
2004, 236–237. (b) Do, Y.-S.; Sun, R.; Kim, H. J.; Yeo, J. E.; Bae, S.-H.;
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(10) Kim, H. J.; Koo, S. Org. Biomol. Chem. 2005, 3, 3479–3481.
(11) Il’ina, I. V.; Volcho, K. P.; Korchagina, D. V.; Barkhash, V. A.;
Salakhutdinov, N. F. Helv. Chim. Acta 2007, 90, 353–368.
(12) Araki, S.; Kambe, S.; Kameda, K.; Hirashita, T. Synthesis 2003,
751–754.
Supporting Information Available. Experimental proce-
dures, characterization data, and 1H NMR and 13C NMR
spectra for all the new compounds. This material is avail-
(13) Katzenellenbogen, J. A.; Corey, E. J. J. Org. Chem. 1972, 37,
1441–1442.
(14) Mechelke, M. F.; Wiemer, D. F. J. Org. Chem. 1999, 64, 4821–
4829.
(15) Kuk, J.; Kim, B. S.; Jung, H.; Choi, S.; Park, J.-Y.; Koo, S.
J. Org. Chem. 2008, 73, 1991–1994.
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