Preparation of propargyl hydroperoxides by regioselective oxidation of allenic zinc reagents with molecular oxygen

Article abstract of DOI:10.1021/jo034743p

Treatment of allenic zinc reagents (R¹R²C=C=C(R ³)ZnL), generated by the reaction of propargyl derivative (R ¹R²C(X)C≡CH) with triorganozincates (R ³₃ZnLi), under oxygen atmosphe

Full text of DOI:10.1021/jo034743p

P r ep a r a tion of P r op a r gyl Hyd r op er oxid es by Regioselective
Oxid a tion of Allen ic Zin c Rea gen ts w ith Molecu la r Oxygen
Toshiro Harada* and Emiko Kutsuwa
Department of Chemistry and Materials Technology, Kyoto Institute of Technology,
Matsugasaki, Sakyo-ku, Kyoto 606-8585, J apan
harada@chem.kit.ac.jp
Received J une 1, 2003
Treatment of allenic zinc reagents (R1R2CdCdC(R3)ZnL), generated by the reaction of propargyl
derivative (R1R2C(X)CtCH) with triorganozincates (R3 ZnLi), under oxygen atmosphere in the
3
presence of ZnCl2 and chlorotrimethylsilane afforded propargyl hydroperoxides (R1R2C(OOH)-
CtCR3) regioselectively. In this reaction, the use of ZnCl2 and chlorotrimethylsilane as additives
is essential for the transformation of the initially generated allenic reagents to more reactive
chlorozinc species.
SCHEME 1
Organozinc compounds have been well-known to react
with molecular oxygen to provide hydroperoxides and/or
alcohols (Scheme 1).1,2 Depending on the reaction condi-
tions, such as solvents, temperatures, and O2 concentra-
tion, initially produced zinc peroxides often serve as
oxidizing reagent to afford zinc alkoxides.3 The oxidation
reaction is of less synthetic utility when the zinc orga-
nometallics are prepared from an alky iodide or bromide,
derived from the corresponding alcohol. On the other
hand, oxidation of organozinc intermediates generated
by homologation reaction of organozinc precursors is a
synthetically useful transformation, as demonstrated by
Knochel et al. in their report of alcohol synthesis from
zinc organometallics prepared by hydro- and carbozin-
cation.1c
SCHEME 2
We previously reported the reaction of triorganozin-
cates with propargylic derivatives 1 leading to the
efficient generation of homologated allenic zinc reagents
2 (Scheme 2).4 The zinc reagents react with a variety of
electrophiles regioselectively at the γ position to give
three component coupling products 3. Although orga-
nozinc compounds with a C(sp2)-Zn bond, such as vinyl
and arylzincs, are reported to show reduced reactivity
toward molecular oxygen in comparison with highly
reactive alkylzincs,1b oxidation of allenic zinc reagents
1, if it proceeds in an SE2′ manner, would provide us with
a method for the preparation of propargyl hydroperox-
ides5 and/or alcohols. In the present study, we investi-
gated the oxidation of allenic zinc reagents generated by
organozincate homologation.
Resu lts a n d Discu ssion
Allenic zinc species 2a was prepared by treatment of
propargyl mesylate 1a with 2 equiv of Bu3ZnLi in THF
at temperatures from -85 to 0 °C (eq 1). The yield of 2a
(1) (a) Nu¨tzel, K. In Methoden der Organischen Chemie; Thieme:
Stuttgart, Germany, 1973; Vol. 13/2a, p 700. (b) Chemla, F.; Normant,
J . F. Tetrahedron Lett. 1995, 36, 3157. (c) Klement, I.; Lu¨tjens, H.;
Knochel, P. Tetrahedron Lett. 1995, 36, 3161-3164. (d) Klement, I.;
Knochel, P. Synlett 1995, 1113.
(2) For the reaction of organometallics with molecular oxygen, see:
Meher-Detweiler, M. Medhoden der Organischen Chemie; Thieme,
Stuttgart, Germany, 1988; Vol. E13, p 175.
(3) Boche, G.; Lohrenz, J . C. Chem. Rev. 2001, 101, 697.
(4) (a) Harada, T.; Katsuhira, T.; Osada, A.; Iwazaki, K.; Maejima,
K. Oku, A. J . Am. Chem. Soc. 1996, 118, 11377. (b) Harada, T.; Oku,
A. In Organozinc Reagents. A Practical Approach; Knochel, P., J ones,
P., Eds.; Oxford University Press: Oxford, NY, 1999; Chapter 6.
is estimated to be 89% by a D2O quench experiment.4a
When the resulting mixture was treated under oxygen
10.1021/jo034743p CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/25/2003
6716
J . Org. Chem. 2003, 68, 6716-6719

Regioselective Oxidation of Allenic Zinc Reagents
SCHEME 3 a
TABLE 1. O2-Oxid a tion of Allen ic Zin c Rea gen t
Gen er a ted by th e Rea ction of P r op a r gyl Mesyla te 1a
w ith Bu 3Zn Li
yield (%)a
ZnCl2
(equiv)
TMSCl
(equiv)
temp
(°C)
entry
3a
4a
1
2
3
4
5b
6
7
8
9
-85
-40
-40
-40
-40
-40
-85
-40
-40
36
6
6
13
34
22
5
0.5
3
49
3
3
3
6
3
0.5
0.5
0.5
3
54
60
50
21
7
<2
a
b
Isolated yield. Propargyl silane 5 was obtained in 60% yield.
a
R ) PhCH2CH2.
presence of chlorotrimethylsilane. While the reaction of
2a without addition of ZnCl2 gave propargylsilane 54a
(entry 5), diorganozinc B generated in the presence of
ZnCl2 (0.5 equiv) reacted selectively with O2 in the
presence of chlorotrimethylsilane (3 equiv) to give hy-
droperoxide 3a (entries 6 and 7). The yields of 3a were
comparable to that obtained in the reaction of chlorozinc
C (entry 4). Further improvement was not obtained
either when an increased amount of chlorotrimethylsi-
lane was employed (entry 8) or when the additive was
used in combination with 3.0 equiv of ZnCl2 (entry 9).
Since the use of a large amount of hygroscopic ZnCl2 for
the generation of chlorozinc C often led to some difficul-
ties in reproducing the yield, the reaction conditions with
chlorotrimethylsilane (3 equiv) in combination with 0.5
equiv of ZnCl2 were chosen as a standard method in the
following study.
atmosphere at -85 °C for 16 h, 2a underwent SE2′ type
reaction with O2 to give propargyl hydroperoxide 3a and
alcohol 4a in 36% and 13% yield, respectively (Table 1,
entry 1). The reaction of 2a with O2 at -40 °C, on the
other hand, afforded alcohol 4a as a major product in 34%
yield (entry 2).
In these reactions, 2 equiv of Bu3ZnLi was employed
for the efficient generation of 2a .4a The resulting allenic
zinc species, therefore, is an equilibrating mixture of
triorganozincates A and diorganozinc B (eq 2).6 Addition
The effect of chlorotrimethylsilane as an additive in
the reaction of diorganozinc B is most simply rationalized
by the in situ formation of chlorozinc reagent C (Scheme
3). Thus, if we assume that diorganozinc B undergoes
reaction with O2 at the more reactive butyl moiety, the
resulting zinc hydroperoxide 6 might be trapped by
chlorotrimethylsilane to give chlorozinc C with the
formation of a trimethylsilylperoxide.
The results summarized in Table 1 suggest relatively
higher reactivity of allenic chlorozinc reagents toward O2
leading to the regioselective formation of propargylic
hydroperoxides. Confirmation of this was obtained by the
reaction of chlorozinc reagent 8 with O2 (eq 3). Chlorozinc
of 0.5 and 3.0 equiv of ZnCl2 may lead to the formation
of diorganozinc B and chlorozinc C species, respectively.
To examine the reactivity of these allenic zinc species
toward O2, reactions of 2a were carried out in the
presence of ZnCl2 as an additive at -40 °C. While the
reaction of diorganozincs B gave propargyl alcohol 4a as
a major product in low yield (entry 3), relatively clean
reaction was observed for chlorozinc C affording hydro-
peroxides 3a in 49% yield together with a small amount
of alcohol 4a (entry 4).
Chlorotrimethylsilane as a Lewis acidic additive has
been reported to be effective in the reaction of organozinc
reagents.8 To improve the efficiency of O2-oxidation of
allenic zinc species, we examined the reaction in the
(5) For the previous synthesis of propargyl hydroperoxides, see: (a)
Milas, N. A.; Mageli, O. L. J . Am. Chem. Soc. 1952, 74, 1471. (b) Khan,
N. A. J . Org. Chem. 1956, 23, 606.
(6) Assuming a rapid ligand transfer,7 organozincates [RCHdCdC-
(Bu)]n(Bu)3-nZnLi (n ) 2, 3), as well as diorganozinc [RCHdCd
C(Bu)]2Zn, should also present in the reaction mixture.
(7) (a) Seitz, L. M.; Brown, T. L. J . Am. Chem. Soc. 1966, 88, 4140.
(b) Seitz, L. M.; Brown, T. L. J . Am. Chem. Soc. 1967, 89, 1602. (c)
Seitz, L. M.; Little, B. F. J . Organomet. Chem. 1969, 18, 227.
(8) (a) Nakamura, E.; Kuwajima, I. J . Am. Chem. Soc. 1984, 106,
3368. (b) Nakamura, E.; Aoki, S.; Sekiya, K.; Oshino, H.; Kuwajima,
I. J . Am. Chem. Soc. 1987, 109, 8056. (c) Tamaru, Y.; Ochiai, H.;
Nakamura, T.; Yoshida, Z. Angew. Chem., Int., Ed. Engl. 1987, 26,
1157.
8 was prepared by lithiation of allene 7 with butyllithium
and transmetalation of the resulting allenic lithium with
ZnCl2.9 Treatment of 8 under O2 atmosphere at -40 °C
gave hydroperoxide 9 in 57% yield.
(9) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes
and Cumulenes; Elsevier: Amsterdam, The Netherlands, 1981; p 33.
J . Org. Chem, Vol. 68, No. 17, 2003 6717

Harada and Kutsuwa
TABLE 2. O2 Oxid a tion of Allen ic Zin c Rea gen ts 2a -g
Gen er a ted by th e Rea ction of P r op a r gyl Der iva tives
1a -c w ith Tr ior ga n ozin ca tes
by treatment with zinc powder in a 1 N HCl-Et2O two-
phase system at 0 °C (Table 2).1c Under these conditions,
for example, alcohol 4a was obtained in 92% from 3a .
When the above transformation was carried out by using
a crude reaction mixture obtained by O2-oxidation of the
corresponding allenic zinc reagent, alcohol 4a was ob-
tained in 56% overall yield from the starting propargylic
mesylate 1a . Hydroperoxides 3a -g and alcohols 4a -g
1
exhibited considerably similar H NMR spectra. However,
in the spectra of 3a -g, hydroperoxy proton appeared as
a broad signal at 7.4-8.2 ppm. Downfield chemical shifts
(ca. 0.3 ppm) were observed in the proton on the R carbon
atom of hydroperoxides 3a -f compared with that in the
corresponding alcohols 4a -f.11
In summary, we have shown that allenic zinc reagents
generated by the reaction of propargylic derivatives 1 and
triorganozincates react regioselectively at the γ position
with a molecular oxygen to give the corresponding
hydroperoxides. To our knowledge, the reaction repre-
sents the first example of selective SE2′ type O2 oxidation
of organometallics. The use of ZnCl2 and chlorotrimeth-
ylsilane as additives was found to be essential to this
reaction for the transformation of the initially generated
allenic reagents to more reactive chlorozinc species.
Exp er im en ta l Section
Ca u tion : Although no problems were encountered handling
the propargyl hydroperoxides employed in this study, they are
potentially explosive. Standard precautions (use of safety
shields, avoidance of heat, light, or metal salts, and perfor-
mance of reactions on minimal scale) should be faithfully
observed.12
a
b
Isolated yield. Overall yield from 1.
Gen er a l P r oced u r e for th e P r ep a r a tion of P r op a r gylic
Hyd r op er oxid es 3a -g. Zinc chloride (0.28 g, 1.0 mmol) was
dissolved in THF (6.6 mL) in a dry Schlenk flask under
nitrogen. The resulting solution was cooled at 0 °C. A solution
of an alkyllithium (6.0 mmol) (BuLi (1.6 M in hexane), sec-
BuLi (0.97 M in cyclohexane, hexane), t-BuLi (1.6 M in
pentane)) was added dropwise via syringe. To the resulting
solution of triorganozincates (2.0 mmol) at -85 °C was added
a solution of propargyl derivative 1a -c4a (0.50 mmol) in THF
(0.70 mL). After being stirred at -85 °C for 15 min, the
mixture was allowed to warm immediately to 0 °C. To the
resulting solution of allenic zinc 2 was successively added a
solution of ZnCl2 (34 mg, 0.25 mmol) in THF (1.0 mL) at 0 °C
and chlorotrimethylsilane (0.19 mL, 1.5 mmol) at -85 °C.
Then, the nitrogen line was exchanged by a thick wall, natural
latex rubber balloon filled with oxygen. The mixture was
allowed to warm to -40 °C during 1 h and stirred further for
15-20 h. The mixture was poured into aqueous 1 N HCl and
extracted with ethyl acetate. The organic layer was washed
successively with aqueous 5% Na2S2O3 and water, dried over
MgSO4, and concentrated in vacuo. The residue was purified
by flash chromatography (SiO2, 5% ethyl acetate in hexane)
to give hydroperoxide 3a -g and a small amount of alcohols
4a -g (2-7%).
Previously, Czernecki et al. reported that a crotylzinc
bromide reacts smoothly with O2 to give a 3:3:4 mixture
of trans-crotyl alcohol, cis-crotyl alcohol, and 1-butene-
3-ol in high yield.10 In contrast to nonregioselective
reaction of the crotylzinc reagent, allenic chlorozinc
reagents react regioselectively with O2 in a SE2′ manner
at the γ position. Organozinc compounds with a C(sp2)-
Zn bond are reported to show low reactivity toward
molecular oxygen.1b The reduced reactivity of allenic zinc
reagents at the sp2 hybridized R carbon could be influ-
ential to the observed regioselctivity.
The scope of the present oxidation of allenic reagents
generated from propargyl derivatives is shown by the
results summarized in Table 2. Allenic zinc reagents 2b,c
bearing sec-butyl and tert-butyl groups at the R carbon
were generated by the reaction of 1a and the correspond-
ing triorganozincates. These reagents gave propargylic
hydroperoxides 3b,c in yields comparable to that for the
reaction with Bu3ZnLi (entries 2 and 3). 1-Cyclohexyl-2-
propynyl mesylate 1b also underwent a similar reaction
to give hydroperoxide 3d -f in ca. 60% yield (entries 4-6).
γ,γ-Disubstituted allenic zinc reagent 2g can be prepared
by the reaction of propargylic chloride 1c with Bu3ZnLi.
2g also reacted with O2 under the present reaction
conditions to give tert-hydroperoxide 3g in 54% yield
(entry 7).
1-P h en yl-4-n on yn -3-yl Hyd r op er oxid e (3a ): 1H NMR δ
0.97 (3H, t, J ) 7.2 Hz), 1.47 (2H, m), 1.57 (2H, m), 2.04 (1H,
m), 2.13 (1H, m), 2.31 (2H, dt, J ) 1.8 and 7.2 Hz), 2.82 (2H,
t, J ) 7.9 Hz), 4.66 (1H, br t, J ) ca. 6 Hz), 7.2-7.3 (5H, m),
8.20 (1H, br); 13C NMR δ 13.6, 18.4, 21.9, 30.6, 31.3, 34.8, 75.8,
For the confirmation of the structure, hydroperoxides
3a -g were converted to the corresponding alcohols 4a -g
(11) Swern, D.; Clements, A. H.; Luong, T. M. Anal. Chem. 1969,
41, 412.
(12) (a) Patnaik, P. A. Comprehensive Guide to the Hazardous
Properties of Chemical Substances; Van Nostrand Reinhold: New York,
1992. (b) Shanley, E. S. In Organic Peroxides; Swern, D., Ed.; Wiley-
Interscience: New York, 1970; Vol. 3, p 341.
(10) Czernecki, S.; Georgoulis, C.; Gross, B.; Pre´vost, C. C. R. Acad.
Sci., Ser. C 1968, 266, 1617.
6718 J . Org. Chem., Vol. 68, No. 17, 2003

Regioselective Oxidation of Allenic Zinc Reagents
77.3, 88.0, 126.0, 128.41, 128.44, 141.1; IR (liquid film) 3425
δ 27.3, 31.0, 31.5, 39.7, 62.0, 79.3, 94.3, 125.9, 128.4, 128.5,
(br), 2235, 1340, 750, 695 cm-1
.
141.6; IR (liquid film) 3320 (br) 2225, 1145, 740, 690 cm-1
;
6-Met h yl-1-p h en yl-4-oct yn -3-yl H yd r op er oxid e (3b ):
1H NMR δ 1.04 (3H, t, J ) 7.4 Hz), 1.22 (3H, d, J ) 7.0 Hz),
1.50 (2H, m), 1.97-2.17 (2H, m), 2.47 (1H, m), 2.80 (2H, t, J
) 6.3 Hz), 4.67 (1H, br t, J ) ca. 6 Hz), 7.2-7.3 (5H, m), 8.15
(1H, br); 13C NMR (125.8 MHz, CDCl3) δ 11.7, 20.6, 27.5, 29.7,
31.4, 34.9, 75.9, 77.4, 92.3, 126.0, 128.42, 128.44, 141.1; IR
MS m/z (rel intensity) 216 (M+, 8), 183 (87), 91 (100); HRMS
calcd for C15H20O 216.1514, found 216.1514.
1-Cycloh exyl-2-h ep tyn -1-ol (4d ): 1H NMR δ 0.89 (3H, t,
J ) 5.0 Hz), 1.00-1.25 (5H, m), 1.35-1.55 (5H, m), 1.65-1.85
(6H, m), 2.20 (2H, dt, J ) 1.8 and 7.0 Hz), 4.12 (1H, d, J ) 5.0
Hz); 13C NMR δ 13.6, 18.4, 21.9, 25.89, 25.92, 26.4, 28.1, 28.6,
30.8, 44.4, 67.5, 80.1, 86.3; IR (liquid film) 3350 (br), 2225,
1005 cm-1; MS m/z (rel intensity) 194 (M+, 4), 137 (65), 111
(100); HRMS calcd for C13H22O 194.1671, found 194.1672.
1-Cycloh exyl-4-m eth yl-2-h exyn -1-ol (4e): 1H NMR δ
0.96 (3H, t, J ) 7.4 Hz), 1.0-1.3 (9H, m, including d (3H, J )
6.9 Hz) at 1.14), 1.41-1.55 (3H, m), 1.65-1.85 (5H, m), 2.38
(1H, m), 4.10 (1H, d, J ) 5.9 Hz); 13C NMR δ 11.8, 20.7, 25.89,
25.93, 26.4, 27.5, 28.0, 28.6, 29.9, 44.4, 67.4, 80.3, 90.6; IR
(liquid film) 3350 (br), 2225, 1010 cm-1; MS m/z (rel intensity)
(liquid film) 3400 (br), 2220, 1325, 740, 690 cm-1
.
6,6-Dim et h yl-1-p h en yl-4-h ep t yn -3-yl Hyd r op er oxid e
(3c): 1H NMR δ 1.17 (9H, s), 1.85-2.15 (2H, m), 2.66 (2H, t,
J ) 6.6 Hz), 4.54 (1H, t, J ) 6.7 Hz), 7.1-7.25 (5H, m), 7.80
(1H, br); 13C NMR δ 27.5, 31.0, 31.4, 34.8, 75.5, 75.9, 96.4,
126.0, 128.45, 128.49, 141.1; IR (liquid film) 3420 (br), 2225,
1355, 740, 690 cm-1
.
1-Cycloh exyl-2-h ep tyn yl Hyd r op er oxid e (3d ): 1H NMR
δ 0.90 (3H, t, J ) 7.4 Hz), 1.05-1.25 (5H, m), 1.45 (2H, m),
1.54 (2H, m), 1.65-1.85 (6H, m), 2.29 (2H, dt, J ) 1.9 and 7.0
Hz), 4.44 (1H, br d, J ) 6.4 Hz), 8.12 (1H, br); 13C NMR δ
13.6, 18.4, 22.0, 25.76, 25.80, 26.3, 28.4, 29.0, 30.7, 40.6, 76.5,
194 (M+, 7), 137 (73), 111 (100); HRMS calcd for C13H22
194.1671, found 194.1676.
O
1-Cycloh exyl-4,4-d im eth yl-2-p en tyn -1-ol (4f): 1H NMR
δ 1.0-1.3 (14H, m, including s (9H) at 1.22), 1.75-1.9 (7H,
m), 4.11 (1H, d, J ) 6.0 Hz); 13C NMR δ 25.9, 26.0, 26.5, 27.4,
28.0, 28.6, 31.0, 44.4, 67.3, 78.46, 94.6; IR (liquid film) 3450
(br), 2225, 1020 cm-1; MS m/z (rel intensity) 194 (M+, 4), 161
(67), 111 (100); HRMS calcd for C13H22O 194.1671, found
194.1676.
81.4, 88.3; IR (liquid film) 3420 (br), 2210, 1325 cm-1
.
1-Cycloh exyl-4-m et h yl-2-h exyn yl
H yd r op er oxid e
(3e): 1H NMR δ 0.99 (3H, t, J ) 7.0 Hz), 1.1-1.3 (8H, m),
1.45-1.5 (2H, m), 1.65-1.80 (6H, m), 2.43 (1H, m), 4.45 (1H,
br d, J ) ca. 6.5 Hz), 8.10 (1H, br); 13C NMR δ 11.8, 20.7, 25.77,
25.81, 26.3, 27.6, 28.3, 29.0, 29.8, 40.6, 76.6, 77.3, 81.4; IR
(liquid film) 3400 (br), 2225, 1330 cm-1
.
1-(1-Hexyn yl)cycloh exa n ol (4g): H NMR δ 0.92 (3H, t,
1
1-Cycloh exyl-4,4-d im eth yl-2-p en tyn yl Hyd r op er oxid e
J ) 7.3 Hz), 1.22-1.28 (1H, m), 1.4-1.6 (9H, m), 1.68 (2H,
m), 1.85-1.9 (3H, m), 2.22 (2H, t, J ) 7.1 Hz); 13C NMR δ
13.6, 18.3, 21.9, 23.5, 25.3, 30.9, 40.3, 68.8, 83.8, 84.8; IR (liquid
film) 3360 (br), 2225, 1060 cm-1; MS m/z (rel intensity) 180
(M+, 15), 137 (100); HRMS calcd for C12H20O 180.1514, found
180.1514.
(3f): 1H NMR δ 1.0-1.3 (14H, m, including s (9H) at 1.27),
1.65-1.85 (6H, m), 4.45 (1H, d, J ) 6.0 Hz), 8.10 (1H, br); 13
C
NMR δ 25.79, 25.82, 26.3, 27.5, 28.3, 29.1, 31.0, 40.6, 74.7,
81.4, 96.7; IR (liquid film) 3420 (br), 2240, 1450, 1260 cm-1
.
1-Hexyn ylcycloh exyl Hyd r op er oxid e (3g): 1H NMR δ
0.94 (3H, t, J ) 7.3 Hz), 1.45-1.7 (12H, m), 1.91 (2H, m), 2.28
(2H, t, J ) 7.2 Hz), 7.40 (1H, br); 13C NMR δ 13.6, 18.3, 21.9,
22.7, 25.4, 30.8, 35.2, 80.09, 81.40, 86.9; IR (liquid film) 3420
5-P h en yl-1-p en tyn -3-yl Hyd r op er oxid e (9). 5-Phenyl-
1,2-pentadiene13,14 (1.0 mmol) was dissolved in THF (3.0 mL)
in a dry Schlenk flask under nitrogen. A solution of BuLi (0.63
mL, 1.0 mmol) was added dropwise via syringe at -80 °C. The
resulting mixture was allowed to warm to -65 °C and stirred
for 30 min. To the resulting solution of allenic lithium was
added a solution of ZnCl2 (0.14 g, 1.0 mmol) in THF (2.0 mL).
After being stirred for 30 min at -65 °C, the mixture was
cooled to -85 °C. Then, the nitrogen line was exchanged by a
thick wall, natural latex rubber balloon filled with oxygen. The
mixture was allowed to warm to -40 °C during 1 h and stirred
further for 18 h. The mixture was poured into aqueous 1 N
HCl and extracted with ether. The organic layer were washed
successively with aqueous 5% Na2S2O3 and water, dried over
MgSO4, and concentrated in vacuo. The residue was purified
by flash chromatography (SiO2, 10% ether in pentane) to give
89.8 mg (51% yield) of 9: 1H NMR δ 2.0-2.2 (2H, m), 2.57
(1H, d, J ) 2.0 Hz), 2.79 (2H, t, J ) 7.5 Hz), 4.61 (1H, dt, J )
2.0 and 7.0 Hz), 7.2-7.4 (5H, m), 8.22 (1H, br); 13C NMR δ
31.2, 34.3, 74.9, 75.2, 81.2, 126.2, 128.47, 128.52, 140.7; IR
(liquid film) 3260 (br), 2110, 1335, 740, 690 cm-1. Reduction
of 9 by treatment with Zn powder in aqueous 1 N HCl-Et2O
gave 5-phenylpent-1-yn-3-ol.4a
(br), 2240, 1340 cm-1
.
Gen er a l P r oced u r e for Con ver sion of Hyd r op er oxid es
3a -g in to Alcoh ols 4a -g. Aqueous 1 N HCl (5.0 mL) was
added to a solution of propargylic hydroperoxide 3a -g (0.5
mmol) in ether (10 mL). To the vigorously stirred mixture at
0 °C was added zinc powder (0.30 g, 0.46 mmol). After being
stirred for 30 min the reaction mixture was filtered and the
filtrate was extracted with ether. The organic layer was dried
over MgSO4 and concentrated in vacuo. The residue was
purified by flash chromatography (SiO2, 5% ethyl acetate in
hexane) to give alcohol 4a -g.
1-P h en yl-4-n on yn -3-ol (4a ): bp 150 °C/0.06 mmHg (Kugel
1
rohr); H NMR δ 0.92 (3H, t, J ) 7.3 Hz), 1.4-1.45 (2H, m),
1.5-1.55 (2H, m), 1.95-2.05 (3H, m), 2.23 (2H, m), 2.82 (2H,
t, J ) 7.9 Hz), 4.36 (1H, m), 7.2-7.3 (5H, m); 13C NMR (125.8
MHz, CDCl3) δ 13.6, 18.3, 21.9, 30.7, 31.5, 39.6, 62.0, 80.9,
86.0, 125.9, 128.4, 128.5, 144.5; IR (liquid film) 3350 (br), 2225,
1030, 745, 695 cm-1; MS m/z (rel intensity) 216 (M+, 14), 141
(20), 91 (100); HRMS calcd for C15H20O 216.1514, found
216.1513.
6-Meth yl-1-p h en yl-4-octyn -3-ol (4b): 1H NMR δ 0.99 (3H,
t, J ) 7.5 Hz), 1.16 (3H, d, J ) 6.9 Hz), 1.45-1.50 (2H, m),
1.80 (1H, br), 1.95-2.05 (2H, m), 2.41 (1H, m), 2.78 (2H, t, J
) 7.9 Hz), 4.38 (1H, br t, J ) ca. 6.5 Hz), 7.15-7.30 (5H, m);
13C NMR δ 11.8, 20.7, 27.5, 29.8, 31.5, 39.8, 62.0, 81.2, 90.3,
125.9, 128.4, 128.5, 141.5; IR (liquid film) 3320 (br), 2220, 1050,
1030, 1010, 745, 695 cm-1; MS m/z (rel intensity) 216 (M+, 18),
159 (100), 91 (90); HRMS calcd for C15H20O 216.1514, found
216.1514.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra for
all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O034743P
(13) Ohno, H.; Miyaura, K.; Tanaka, T.; Oishi, S.; Toda, A.; Take-
moto, Y.; Fujii, N.; Ibuka, T. J . Org. Chem. 2002, 67, 1359.
(14) 5-Phenyl-1,2-pentadiene was prepared in 63% yield by CuBr-
mediated reaction of methyl propargyl ether with PhCH2CH2MgCl.15
(15) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes
and Cumulenes; Elsevier: Amsterdam, The Netherlands, 1981; p 157.
6,6-Dim eth yl-1-p h en yl-4-h ep tyn -3-ol (4c): 1H NMR δ
1.24 (9H, s), 1.74 (1H, br), 1.95-2.05 (2H, m), 2.79 (2H, t, J )
7.9 Hz), 4.35 (1H, t, J ) 6.5 Hz), 7.15-7.3 (5H, m); 13C NMR
J . Org. Chem, Vol. 68, No. 17, 2003 6719