A PhSeCl-mediated allylic oxidation of prenyl moiety: A convenient method for the construction of 3-isopenten-2-ol unit

Article abstract of DOI:10.1248/cpb.56.404

A phenylselenenyl chloride (PhSeCl)-mediated allylic oxidation to give allylically rearranged alcohol has been developed. A possible mechanism for the present reaction is generation of allylic selenide from prenyl moiety via [1,3]-sigmatropic rearrangement, followed by oxidation and [2,3]-sigmatropic rearrangement to afford 3-isopenten-2-ol.

Full text of DOI:10.1248/cpb.56.404

404
Notes
Chem. Pharm. Bull. 56(3) 404—406 (2008)
Vol. 56, No. 3
A PhSeCl-Mediated Allylic Oxidation of Prenyl Moiety: A Convenient
Method for the Construction of 3-Isopenten-2-ol Unit
*
Motoko OSHIDA, Tomoaki NAKAMURA, Atsuo NAKAZAKI, and Susumu KOBAYASHI
Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI); 2641 Yamazaki, Noda, Chiba 278–8510,
Japan. Received December 11, 2007; accepted January 8, 2008; published online January 10, 2008
A phenylselenenyl chloride (PhSeCl)-mediated allylic oxidation to give allylically rearranged alcohol has
been developed. A possible mechanism for the present reaction is generation of allylic selenide from prenyl moi-
ety via [1,3]-sigmatropic rearrangement, followed by oxidation and [2,3]-sigmatropic rearrangement to afford 3-
isopenten-2-ol.
Key words allylic oxidation; trisubstituted alkene; sigmatropic rearrangement; phenylselenenyl chloride; prenyl moiety; 3-
isopenten-2-ol
A number of methodologies for the oxidation of alkenes to mediated allylic oxidation of alkenes.
allylic alcohols have been developed (Fig. 1).1) For example,
At first, we investigated the optimization of this oxidation
selenium dioxide and chromate reagents generally oxidize using citronellyl acetate 3 as a model substrate. As shown in
the allylic position without rearrangement of the carbon–car- Table 1, the reaction of 3 proceeded in a similar manner
bon double bond. In contrast, singlet oxygen affords the al- (PhSeCl–pyridine, 50 °C) as 1 to give the corresponding allyl
lylic alcohol with the rearrangement of the carbon–carbon alcohol 4 in 66% yield (entry 1).8) When other readily avail-
double bond. Epoxidation of alkenes followed by epoxide able phenylselenium reagents were applied in the reaction,
opening with metal amide is also well-known.2—6)
neither phenylselenenyl bromide (PhSeBr) nor N-PSP (N-
During the course of the synthetic investigation of diversi- phenylselenenylphthalimide) were effective for this transfor-
folin, we found that treatment of g,d-unsaturated carboxylic mation (entries 2, 3). Although the reactions in benzene, tri-
acid 1 with 2.0 eq of phenylselenenyl chloride (PhSeCl) in ethylamine, and 2,6-lutidine yielded poor results, the reaction
pyridine at 50 °C, followed by oxidation with hydrogen per- in acetonitrile gave 4 in 31% yield (entries 4—7). As shown
oxide, provided g-butyrolactone 2 in 44% yield (Chart 1).7) in entries 8 and 9, higher reaction temperatures resulted in a
This result means that allylic oxidation of the trisubstituted slight decrease in the yield probably due to decomposition of
alkene proceeded in addition to the planned selenolactoniza- 4. These results indicate that treatment with PhSeCl in pyri-
tion of the 4-alkenoic acid moiety. Herein we wish to report dine at 50 °C gave the best result.
the scope and limitations of the phenylselenenyl chloride-
With optimum conditions established, we next carried out
the oxidation of a variety of other substrates 5a—j as shown
in Table 2.8) The reaction of 2-methyl-2-undecene (5a) gave
the corresponding allyl alcohol 6a in 55% yield (entry 1),
while 1,1-diethyl substituted derivative 5b gave 6b in a very
low yield due to steric hindrance around the trisubstituted
olefin (entry 2). In contrast, cyclohexylidene derivative 5c
produced 6c in higher yield than in the case of 5b (entry 3).
This result might be attributed to inflexibility of the cyclo-
hexane ring in 5c. Although the allylic oxidations of nerol 5d
and citronerol 5f afforded the corresponding diols 6d and 6f
Table 1. Optimization
Fig. 1. Allylic Oxidations
Entry
PhSeX
Solvent
Temp. (°C)
Yield (%)
1
2
3
4
5
6
7
8
9
PhSeCl
PhSeBr
N-PSPa)
PhSeCl
PhSeCl
PhSeCl
PhSeCl
PhSeCl
PhSeCl
Pyridine
Pyridine
Pyridine
MeCN
Benzene
2,6-Lutidine
Et3N
50
50
50
50
50
50
50
80
100
66
6
N.R.b)
31
3
N.R.b)
N.R.b)
62
Pyridine
Pyridine
48
Chart 1
a) N-Phenylselenenylphthalimide. b) No reaction.
∗ To whom correspondence should be addressed. e-mail: kobayash@rs.noda.tus.ac.jp
© 2008 Pharmaceutical Society of Japan

March 2008
405
Table 2. Limitation
Entrya)
Substrate
Product
Yield (%)
55
1
2
3
6b)
37
Chart 2. NOE Experiments
4
5
28
64
6
7
26
66
8
9
0d)
59
10
11
6c,d)
10
a) i) PhSeCl (1 eq), pyridine (0.1 M), 50 °C; ii) H2O2, THF (0.1 M), 0 °C to rt. b)
Small amount of the eliminated diene and unrearranged allyl alcohol was obtained. c)
Approximately 30% of starting material was recovered. d) Selenoetherificated prod-
ucts were obtained.
Chart 3. A Plausible Mechanism
only in 28% and 26% yields, respectively (entries 4, 6).
Yields were increased when the hydroxyl groups in sub-
strates were protected (entries 5, 7). When olefinic alcohol 5g
was treated with PhSeCl, selenoetherification proceeded and
no allylic alcohol 6g was formed, but the corresponding al-
lylic alcohol could be obtained in 59% yield by protecting
the hydroxyl group (entries 8, 9). The oxidation of cyclic
trisubstituted endo-alkenes such as a-terpineol (5i) and its
silyl derivative (5j) gave the corresponding allyl alcohols in
poor yield along with approximately 30% recovery of start-
ing alkene (entries 10, 11). From these results on the scope
Chart 4
and limitations of this reaction, the present PhSeCl–pyridine lylic selenide B,9) formed by reaction of the trisubstituted
methodology was found to be effective for the oxidation of a alkene with phenylselenenyl chloride in pyridine, is in equi-
prenyl unit to a 3-isopenten-2-ol unit.
librium with thermodynamically more stable endo-alkenyl al-
Further experimentation was also undertaken to elucidate lylic selenide C via a [1,3]-sigmatropic rearrangement.10,11)
the mechanism of the above allylic oxidation (Chart 2). Thus, The endo-alkenyl selenide C is oxidized by H2O2 to selenox-
the treatment of 2-methyl-2-undecene (5a) with PhSeCl in ide D, which simultaneously undergoes [2,3]-sigmatropic
pyridine afforded allyl selenide 7 as an inseparable mixture rearrangement12—14) to afford 3-isopenten-2-ol E. It should
of geometric isomers (E/Zꢀca. 2 : 1). Two singlet peaks at d be emphasized that one-pot transformation of trisubstituted
1
3.51 and 3.56 in H-NMR spectra are assigned to an allylic alkenes to endo-alkenyl allylic selenides involving [1,3]-sig-
methylene group adjacent to the phenylselenenyl group of E- matropic rearrangement has not been reported.15)
7 and Z-7, respectively. The geometry of each isomer was de-
In summary, we have described a method for a transforma-
termined by nuclear Overhouser effect (NOE) experiments as tion of trisubstituted olefins to allylic alcohol.16) This method
shown in Chart 2. The resulting allyl selenide 7 was treated is particularly useful for converting the prenyl group into a 3-
with hydrogen peroxide to afford 2-methyl-1-undecen-3-ol isopenten-2-ol unit.
(6a).
General Procedure Phenylselenenyl chloride was added
Based on the above results, a plausible mechanism of the to the solution of 2-methyl-2-undecene (5a) in pyridine at
present allylic oxidation is shown in Chart 3. exo-Alkenyl al- 0 °C. The mixture was stirred at 50 °C for 12 h. The resulting

406
Vol. 56, No. 3
and mass spectra.
mixture was poured into a saturated aqueous copper sulfate,
and extracted with diethyl ether. The combined organic layer
was dried over anhydrous sodium sulfate, concentrated, and
purified by a short-path silica gel column chromatography
9) A similar observation in the SeO2-mediated allylic oxidation of
linalool has been reported. Feliciano A. S., Medarde M., López J. L.,
Pereira J. A. P., Caballero E., Perales A., Tetrahedron, 45, 5073—5080
(1989).
(hexane) to afford allyl selenide 7. The resulting allylic se- 10) Clive D. L. J., Tetrahedron, 34, 1049—1132 (1978).
11) Lewis R. T., Motherwell W. B., Tetrahedron, 48, 1465—1484 (1992).
12) Billard T., Langlois B. R., Tetrahedron, 55, 8065—8074 (1999).
13) Pearson A. J., Ray T., Richards I. C., Clardy J., Silveira L., Tetrahedron
lenide 7 was treated by 30% aqueous hydrogen peroxide so-
lution in tetrahydrofuran at 0 °C. The reaction mixture was
extracted with diethyl ether, washed with brine, dried over
Lett., 24, 5827—5830 (1983).
anhydrous sodium sulfate, concentrated under the reduced
pressure, and purified by a silica gel column chromatography
to afford allylic alcohol 6a (55% yield).
14) Vedejs E., Rodgers J. D., Wittenberger J., Tetrahedron Lett., 29,
2287—2290 (1988).
15) To the best of our knowledge, although only one example for this type
of PhSeCl-mediated reaction was found, it was the reaction of the cy-
clopropylidene-type tetrasubstituted alkenes without accompanying
[1,3]-sigmatropic rearrangement. Liu L.-P., Shi M., J. Org. Chem., 69,
2805—2808 (2004).
16) In the case of disubstituted olefins 8a and 8b, each gave rise to an ap-
proximate 1 : 1 mixture of b-phenylseleno alcohols 9a, 9b and 9c, 9d,
respectively, instead of the corresponding allyl selenide (Chart 4). The
planar structure of 9 was determined by NMR (1H and 13C), IR and
HR-MS. When the stereochemistry of 9 was speculated as shown
based on the reaction mechanism. Additionally, when a mixture of 5a
and 8b was treated with PhSeCl, allylic selenide 7 derived from 5a
was obtained, and a significant amount of 8b was recovered. This re-
sult shows that this reaction might be useful for the chemoselective
transformation of trisubstituted olefins by PhSeCl.
References and Notes
1) Bulman Page P. C., McCarthy T. J., “Comprehensive Organic Synthe-
sis,” Vol. 7, ed. by Trost B. M., Pergamon Press, Oxford, 1991, pp.
83—117.
2) Yasuda A., Tanaka S., Oshima K., Yamamoto H., Nozaki H., J. Am.
Chem. Soc., 96, 6513—6514 (1974).
3) Eschinasi E. H., J. Org. Chem., 35, 1598—1600 (1970).
4) Asami M., Chem. Lett., 1984, 829—832 (1984).
5) Whitesell J. K., Felman S. W., J. Org. Chem., 45, 755—756 (1980).
6) Doris E., Dechoux L., Mioskowski C., Tetrahedron Lett., 35, 7943—
7946 (1994).
7) Nakamura T., Oshida M., Nomura T., Nakazaki A., Kobayashi S., Org.
Lett., 9, 5533—5536 (2007).
8) All new compounds were fully characterized by 1H- and 13C-NMR, IR