An efficient procedure for the 1,3-transposition of allylic alcohols based on lithium naphthalenide induced reductive elimination of epoxy mesylates

Article abstract of DOI:10.1055/s-2008-1032092

An efficient protocol for the 1,3-transposition of allylic alcohols has been developed. The method is based on the pretransformation of allylic alcohols into the corresponding epoxy mesylates, followed by the reductive elimination of the resulting epoxy mesylates by using lithium naphthalenide (LN) as a reducing agent. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032092

LETTER
621
An Efficient Procedure for the 1,3-Transposition of Allylic Alcohols Based on
Lithium Naphthalenide Induced Reductive Elimination of Epoxy Mesylates
Efficient
P
rocedur
e
e
for the 1,3
n
-
Transpositi
-
onof
A
l
K
lylic
A
lcohols u Wu,a Hsing-Jang Liu,*a Jia-Liang Zhu*b
a
Department of Chemistry, National Tsing Hua University, Hsinchu 30043, Taiwan
E-mail: hjliu@mx.nthu.edu.tw
b
Department of Chemistry, National Dong-Hwa University, Hualien 974, Taiwan
Fax +886(3)8633570; E-mail: jlzhu@mail.ndhu.edu.tw
Received 25 November 2007
OMs
OH
1) MCPBA (1.2 equiv), CH2Cl2,
0 °C, 40 min, 83%
Abstract: An efficient protocol for the 1,3-transposition of allylic
alcohols has been developed. The method is based on the pretrans-
formation of allylic alcohols into the corresponding epoxy mesy-
lates, followed by the reductive elimination of the resulting epoxy
mesylates by using lithium naphthalenide (LN) as a reducing agent.
O
2) MsCl (1.2 equiv), Et3N (1.2 equiv),
CH2Cl2, 0 °C, 1 h, 90%
1a
Key words: allylic alcohols, 1,3-transposition, epoxy mesylates,
reductive elimination, lithium naphthalenide
LN (3 equiv), THF
–25 °C, 10 min
84%
The 1,3-transposition of double bond and hydroxyl func-
tionalities of allylic alcohols is an important process in
synthetic chemistry. Among numerous methods devel-
oped for this transformation,1 those based on preconver-
sion of allylic alcohols into the corresponding epoxy
tosylates or mesylates, followed by generation of transpo-
sitioned allylic alcohols from these intermediates are con-
sidered to be attractive options. In accordance with this
strategy, several reagent systems such as Te/NaBH4, Te/
LiEt3BH, Te/HOCH2SO2Na,2 NaI,3a NaI/Zn/AcOH3b and
dissolving metals in liquid ammonia,4,5 have been report-
ed to convert epoxy tosylates or mesylates into alcohol
products. Of these procedures, the dissolving-metal-medi-
ated reductive elimination of epoxy sulfonate esters,
which was first described by Nozaki,4 has shown to be the
most useful5 in terms of relatively wide application scope.
However, this operation is inevitably plagued with the dif-
ficulty in the handling of active metals (Na, Li, Ca) as well
as the highly volatile solvent (liquid NH3). Furthermore,
in some cases, the reactions are complicated by the com-
petitive S–O bond cleavage,5d or the loss of stereochemis-
try about the double bond in the electron-transfer
process.5e As such, a good deal of interest exists in devel-
oping more efficient and operationally simple procedures
to circumvent these limitations. Herein, we wish to report
a highly facile and efficient protocol for the 1,3-transposi-
tion of allylic alcohols by utilizing lithium naphthalenide
(LN) induced reductive elimination of epoxy mesylates as
a key operation. As a well-known electron-donating spe-
cies,6 LN reagent is believed to play a role analogous to
that of dissolving metals in the reductive elimination pro-
cess. However, as described below, it is definitely much
more easily handled and appears to have broader function-
HO
2a
Scheme 1 Preparation and LN-induced reductive elimination of 1a
al group compatibility. To date, only a few cases of using
sodium naphthalenide to effect the reductive elimination
reaction have been reported, but only a moderate yield of
the alcoholic product was obtained.5f,7 The use of LN as a
reducing agent for such transformation, to our knowledge,
is unprecedented.
As a typical example, our method is illustrated by the
transformation of 3,5,5-trimethylcyclohex-2-enol into the
transpositioned allylic alcohol 2a (Scheme 1). The epoxi-
dation of the starting alcohol using m-chloroperoxybenzo-
ic acid (MCPBA)8 followed by the mesylation of the
resulting epoxy alcohol with methanesulfonyl chloride
(MsCl) in the presence of triethylamine could easily fur-
nish the precursor 1a.4,9 The LN-induced reductive elimi-
nation reaction of 1a turned out to be successful. Upon the
treatment with LN (3 equiv) in THF under the mild reac-
tion conditions (–25 °C), 1a could be readily (10 min)
converted into the transpositioned allylic alcohol 2a in
high yield (84%).10,11
The reductive elimination process proved to be general
when applied to an array of epoxy mesylates (Table 1).
Substrates 1b–e were prepared similarly as 1a from com-
mercially available (+)-trans-pulegol, (–)-pin-2-en-10-ol,
trans-3,7,11,15-tetramethylhexadec-2-en-1-ol and trans-
1-phenylpent-3-en-2-ol. Under the conditions, the reduc-
tive elimination reactions of these compounds took place
smoothly to afford the desired products 2b–e in good to
high yields (entries 1–4). It is noteworthy that the current
reaction conditions displayed a high tolerance for the sub-
strate bearing a phenyl group (1e, entry 4), with which the
conditions of dissolving metals in liquid ammonia are pre-
SYNLETT 2008, No. 4, pp 0621–0623
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x.
x
x.
2
0
0
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Advanced online publication: 12.02.2008
DOI: 10.1055/s-2008-1032092; Art ID: W20507ST
© Georg Thieme Verlag Stuttgart · New York

622
Y.-K. Wu et al.
LETTER
mer exclusively in good yield. In addition, the procedure
was also attempted on several optically active epoxy mes-
ylates 1f–h synthesized from trans-3,7-dimethylocta-2,6-
dien-1-ol, cyclohex-1-enylmethanol and trans-hex-2-en-
1-ol by the Sharpless asymmetric epoxidation using (–)-
diethyl tartrate (1f and 1g) or (+)-diethyl tartrate (1h), tert-
butyl hydroperoxide (TBHP) and titanium(IV) isopro-
poxide [Ti(Oi-Pr)4] as the reagents,12 and the subsequent
mesylation of the resulting chiral epoxy alcohols with
MsCl and triethylamine. Once submitted to the reductive
elimination reactions, these chiral substrates were all effi-
ciently transferred into the corresponding optically active
allylic alcohols 2f–h in 74–85% yields and 51–92% ee
(entries 5–7). Therefore, through such combined opera-
tions, the generation of chiral allylic alcohols from non-
chiral substrates can be easily attended. Furthermore, the
versatility of the procedure has also been demonstrated by
the sterically demanding transformation of (1R,5S)-(–)-
cis-carveol into (1S,5R)-(+)-cis-carveol (2i). According to
the previous report, the reductive elimination of 1i derived
from (–)-cis-carveol by using dissolving sodium in liquid
ammonia or sodium naphthalenide as the reducing
agents5f afforded 2i only in 57% and 54% yields, respec-
tively. In our case (entry 8), a much higher yield (84%) of
2i was obtained with the employment of LN. The high
yield could possibly be attributed to the efficient epoxide
ring opening facilitated by the coordination of a lithium
ion with the epoxy oxygen atom in a lithium-ion-rich me-
dia.13
Table 1 Reductive Elimination of Epoxy Mesylates with LN
OMs
OH
LN (3 equiv), THF
–25 °C, 10 min
O
Entry Substrate
Producta
Yield (%),b
ee (%)
1c
83
OMs
O
OH
1b
1c
2b
2c
OMs
OMs
2d
80
84
O
OH
OH
O
3
C15H31
C15H31
2d
1d
O
4
5
70
OH
OMs
2e
1e
OH
O
OMs
85, 92
The products 2a–i were all purified by flash chromatogra-
phy and their spectral data (1H, 13C NMR) were shown to
agree well with those previously described in the litera-
ture.14 The ee values of 2f–i were determined based on the
reported optical rotations of the pure enatiomers.2b,5f,14h
2f
1f
OMs
O
6
7
82, 88
74, 51
OH
In conclusion, the LN-promoted reductive elimination of
epoxy mesylates has been efficiently applied as a key op-
eration into the process of 1,3-shift of allylic alcohols. In
comparison with the precedents developed for the same
objective, our method appears to be superior in terms of
operational simplicity, broad substrate diversity and rela-
tively high yields.
1g
2g
OH
O
OMs
O
1h
2h
MsO
OH
Acknowledgment
8
84, 99
We are grateful to the National Science Council of Republic of Chi-
na and the National Tsing Hua University for financial support.
1i
2i
a Products 2b–i were characterized by the comparison of their 1H, 13
NMR spectral data with those reported in the corresponding litera-
ture.14b–i,
C
References and Notes
(1) Larock, R. C. Comprehensive Organic Transformation, 2nd
ed.; Wiley-VCH: Weinheim, 1999, 227–228.
(2) (a) Pepito, A. S.; Dittmer, D. C. J. Org. Chem. 1994, 59,
4311. (b) Dittmer, D. C.; Discordia, R. P.; Zhang, Y.;
Murphy, C. K.; Kumar, A.; Pepito, A. S.; Wang, Y. J. Org.
Chem. 1993, 58, 718.
b Yield refers to the pure isolated product.
c From (+)-trans-pulegol, 1b was obtained as a mixture of two diaste-
reoisomers in 1:1 ratio.
d From (–)-pin-2-en-10-ol, 1c was obtained as a single stereoisomer.
(3) (a) Lee, E.; Lee, Y. R.; Moon, B.; Kwon, O.; Shim, M. S.;
Yun, J. S. J. Org. Chem. 1994, 59, 1444. (b) Mori, K.;
Ueda, H. Tetrahedron 1981, 37, 2581.
(4) Yasuda, A.; Yamamoto, H.; Nozaki, H. Tetrahedron Lett.
1976, 2621.
dictably not compatible due to the potentially competing
Birch reduction. Moreover, in entry 4, the reaction pro-
ceeded in a stereoselective fashion to provide the E-iso-
Synlett 2008, No. 4, 621–623 © Thieme Stuttgart · New York

LETTER
Efficient Procedure for the 1,3-Transposition of Allylic Alcohols
623
(5) For some examples, see: (a) Marshall, J. A.; Jenson, T. M. J.
Org. Chem. 1984, 49, 1707. (b) Paquette, L. A.; Ham, W. H.
J. Am. Chem. Soc. 1987, 109, 3025. (c) Marshall, J. A.;
Robinson, E. D.; Adams, R. D. Tetrahedron Lett. 1988, 29,
4913. (d) Marshall, J. A.; Robinson, E. D.; Robinson, E. D.;
Lebreton, J. J. Org. Chem. 1990, 55, 227. (e) Kocienski, P.
J.; Tideswell, J. Synth. Commun. 1979, 9, 411. (f) Yasuda,
H.; Yamamoto, H.; Nozaki, H. Bull. Chem. Soc. Jpn. 1979,
52, 1757.
(6) For some examples of using LN as a reducing reagent, see:
(a) Guijarro, A.; Roman, D. J.; Yus, M. Tetrahedron 1993,
49, 469. (b) Guijarro, A.; Yus, M. Tetrahedron Lett. 1994,
35, 253. (c) Kondo, Y.; Murata, N.; Sakamoto, T.
Heterocycles 1994, 37, 1467. (d) Zhu, J. L.; Shia, K. S.; Liu,
H. J. Chem. Commun. 2000, 1599. (e) Chien, C. F.; Wu, J.
D.; Ly, T. W.; Shia, K. S.; Liu, H. J. Chem. Commun. 2002,
248.
concentrated. Purification by chromatography on silica gel
(hexane; EtOAc–hexane, 1:10) afforded 1,5,5-trimethyl-
cyclohex-2-enol (2a) as a viscous oil (291 mg, 84%). IR
(KBr): 3490, 1675 cm–1. 1H NMR (400 MHz, CDCl3): d =
5.66 (dt, J = 1.5, 9.9 Hz, 1 H), 5.69 (d, J = 9.9 Hz, 1 H), 1.79
(dd, J = 1.5, 15.1 Hz, 1 H), 1.77 (dd, J = 1.5, 15.1 Hz, 1 H),
1.64 (d, J = 14.0 Hz, 1 H), 1.53 (d, J = 14.0 Hz, 1 H), 1.24
(s, 3 H), 1.02 (s, 3 H), 0.93 (s, 3 H). 13C NMR (100 MHz,
CDCl3): d = 132.4, 126.9, 68.2, 50.4, 38.9, 31.0, 30.9, 29.8,
27.6. HRMS (EI): m/z [M]+ calcd for C9H16O: 140.1201;
found: 140.1204.
(11) For preparing a stock solution of LN, see: Liu, H. J.; Yip, J.;
Shia, K. S. Tetrahedron Lett. 1997, 38, 2253.
(12) (a) Sharpless, K. B.; Michaelson, R. C. J. Am. Chem. Soc.
1973, 95, 6136. (b) Sharpless, K. B.; Hanson, R. M. J. Org.
Chem. 1986, 51, 1922.
(13) Mordini, A.; Rayana, E. B.; Margot, C.; Schlosser, M.
Tetrahedron 1990, 46, 2401.
(7) Bannai, K.; Tanaka, T.; Okamura, N.; Hazato, A.; Sugiura,
S.; Manabe, K.; Tomimori, K.; Kurozumi, S. Tetrahedron
Lett. 1986, 27, 6353.
(14) (a) Magnusson, G.; Thoren, S. J. J. Org. Chem. 1973, 38,
1380. (b) Jia, Y. X.; Li, X.; Wu, B.; Zhao, X. Z.; Tu, Y. Q.
Tetrahedron 2002, 58, 1697. (c) Motherwell, W. B.;
Bingham, M. J.; Pothier, J.; Six, Y. Tetrahedron 2004, 60,
3231. (d) Brownstein, S.; Burton, G. W.; Hughes, L.; Ingold,
K. U. J. Org. Chem. 1989, 54, 560. (e) Roush, W. R.;
Straub, J. A.; Brown, R. J. J. Org. Chem. 1987, 52, 5127.
(f) Kumar, A.; Dittmer, D. C. Tetrahedron Lett. 1994, 35,
5583. (g) Alcaraz, L.; Cridland, A.; Kinchin, E. Org. Lett.
2001, 3, 4051. (h) Martin, V. S.; Ode, J. M.; Jesus, M.;
Palazon, J. M.; Soler, M. A. Tetrahedron: Asymmetry 1992,
3, 573. (i) Carvero, R. M.; Gonzalez-Sierra, M.; Labadie, G.
R. Helv. Chim. Acta 2003, 86, 2741.
(8) Kaneti, I. Tetrahedron 1986, 42, 4017.
(9) The stereochemistry of 1a was elucidated based on the
coupling constant in the 1H NMR spectrum.
(10) Typical Procedure for the Reductive Elimination of
Epoxy Mesylates: A stock solution of LN11 in THF (0.365
M, 20.4 mL, 7.43 mmol) precooled to –25 °C was quickly
added by syringe to a solution of 1a (580 mg, 2.48 mmol) in
anhyd THF (5 mL) at –25 °C under a nitrogen atmosphere.
The resulting dark mixture was stirred at –25 °C for 10 min,
then was quenched with H2O (10 mL) and extracted with
EtOAc (2 × 20 mL). The combined extracts were washed
with sat. aq NaCl (10 mL), dried with Na2SO4 and
Synlett 2008, No. 4, 621–623 © Thieme Stuttgart · New York

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