Benzotriazole-mediated [2,3]-wittig rearrangement. General and stereocontrolled syntheses of homoallyl alcohols and β,γ-unsaturated ketones

Article abstract of DOI:10.1021/jo960019d

Readily accessible allyl 1-(benzotriazol-1-yl)alkyl ethers (13 and 19), upon treatment with 2.5 equiv of nucleophilic lithium reagents, give secondary and tertiary homoallyl alcohols (16 and 21), respectively, exclusively in the E configuration in excellent yields. This is achieved by deprotonation followed by [2,3]-Wittig rearrangement, departure of the benzotriazolyl group, and then nucleophilic addition to the resulting carbonyl compound. Following a similar protocol, primary E-homoallyl alcohols 18 are prepared in good yield by the reaction of ethers 13 with LDA in the presence of NaBH₄. Our approach complements the stereochemical Z-selective syntheses of primary homoallyl alcohols of Still and of Bruckner. Wittig rearrangement of the anions of 19 generated with LDA analogously furnishes E-β,γ-unsaturated ketones 20 in excellent yields.

Full text of DOI:10.1021/jo960019d

J . Org. Chem. 1996, 61, 4035-4039
4035
Ben zotr ia zole-Med ia ted [2,3]-Wittig Rea r r a n gem en t. Gen er a l a n d
Ster eocon tr olled Syn th eses of Hom oa llyl Alcoh ols a n d
â,γ-Un sa tu r a ted Keton es
Alan R. Katritzky,* Hong Wu, and Linghong Xie
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received J anuary 2, 1996X
Readily accessible allyl 1-(benzotriazol-1-yl)alkyl ethers (13 and 19), upon treatment with 2.5 equiv
of nucleophilic lithium reagents, give secondary and tertiary homoallyl alcohols (16 and 21),
respectively, exclusively in the E configuration in excellent yields. This is achieved by deprotonation
followed by [2,3]-Wittig rearrangement, departure of the benzotriazolyl group, and then nucleophilic
addition to the resulting carbonyl compound. Following a similar protocol, primary E-homoallyl
alcohols 18 are prepared in good yield by the reaction of ethers 13 with LDA in the presence of
NaBH4. Our approach complements the stereochemical Z-selective syntheses of primary homoallyl
alcohols of Still and of Bruckner. Wittig rearrangement of the anions of 19 generated with LDA
analogously furnishes E-â,γ-unsaturated ketones 20 in excellent yields.
Sch em e 1
In tr od u ction
[2,3]-Wittig rearrangement has become a powerful
strategy in organic chemistry, as demonstrated by its
numerous applications in natural product synthesis.1,2
One of its attractive features is the stereoselective
generation of a double bond due to a concerted, highly
ordered transition state.1,3,4 While the parent lithio
methyl allyl ethers normally give, predominantly or
exclusively, Z-homoallyl alcohols, analogs in which the
methyl group carries a G substituent usually favor the
formation of E isomers, especially when G is a “hydro-
carbon” (vinyl, alkynyl, aryl, alkyl) (Scheme 1). These
trends are accommodated by the favored transition state
configurations.1,4
Sch em e 2
[2,3]-Wittig rearrangements of various allyl ethers 5
(Scheme 2) to provide a wide range of homoallyl alcohols
have been reported.1 The chemical and sterical outcomes
of the rearrangements largely depend on the nature of
the G substituent on the migrating terminus in 5 as
shown by the following classification:
(i) G is a n E lect r on -Wit h d r a w in g Gr ou p (e.g.,
COOH,5 CONR2,6 p r op a r gyl7 a n d Ar 8 ). These groups
facilitate the rearrangement by promoting the formation
of the intermediate anions 2 to furnish R-G-substituted
homoallyl alcohols 1. However, since the G group
remains in the molecule after the rearrangement, reac-
X Abstract published in Advance ACS Abstracts, May 15, 1996.
(1) For reviews, see: (a) Mikami, K.; Nakai, T. Synthesis 1991, 594.
(b) Nakai, T.; Mikami, K. Chem. Rev. 1986, 86, 885. (c) Marshall, J .
A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: New York, 1991; Vol. 3, p 975. (d) Bruckner, R. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: New York, 1991; Vol. 6, p 873.
(2) For examples, see: (a) Sugimura, T.; Paquette, L. A. J . Am.
Chem. Soc. 1987, 109, 3017. (b) Marshall, J . A.; Lebreton, J . J . Am.
Chem. Soc. 1988, 110, 2925. (c) Bruckner, R. Tetrahedron Lett. 1988,
29, 5747.
(3) Wu, Y.-D.; Houk, K. N.; Marshall, J . A. J . Org. Chem. 1990, 55,
1421.
(4) Keiner, P.; Bruckner, R. Tetrahedron 1994, 50, 13417.
(5) Nakai, T.; Mikami, K.; Taya, S.; Kimura, Y.; Mimura, T.
Tetrahedron Lett. 1981, 22, 69.
tions of this type are restricted to the preparation of
certain specific homoallyl alcohols.
(ii) G Ca n Be Exch a n ged for a Lith iu m Atom by
th e Action of Bu Li (e.g., Sn Bu 3 a n d SP h ). Still et al.
reported a convenient Z-selective access to primary
homoallyl alcohols 3 (R2 ) H) from stannylated ethers 5
(R2 ) H, G ) SnBu3) via tin/lithium exchange and
rearrangement.9,10 A similar transformation was achieved
by Bruckner et al. via a reductive cleavage of allyl
(6) Mikami, K.; Takahashi, O.; Kasuga, T.; Nakai, T. Chem. Lett.
1985, 1729.
(7) Sayo, N.; Shirai, F.; Nakai, T. Chem. Lett. 1984, 255.
(8) Makisumi, Y.; Notzumoto, S. Tetrahedron Lett. 1966, 6393.
(9) Still, W. C.; Mitra, A. J . Am. Chem. Soc. 1978, 100, 1927.
S0022-3263(96)00019-9 CCC: $12.00 © 1996 American Chemical Society

4036 J . Org. Chem., Vol. 61, No. 12, 1996
Katritzky et al.
Sch em e 3
Sch em e 4
(phenylthio)methyl ethers 5 (R2 ) H, G ) SPh) and
subsequent rearrangement.11 This methodology has been
further extended to the rearrangement of allyl (phenyl-
thio)alkyl ethers 5 (R2 ) alkyl, G ) SPh) to provide
secondary homoallyl alcohols with E configuration.4,12
However, tertiary homoallyl alcohols and primary homo-
allyl alcohols with E selectivity are not accessible by these
approaches.
(iii) G F u n ction s a s Both a n Electr on -With d r a w -
in g a n d a Lea vin g Gr ou p in th e Rea r r a n gem en t
P r ocess (e.g., su lfon yl gr ou p ). The anions 7 of (allyl-
oxy)methyl sulfones 5 (R2 ) H, G ) p-Ts) undergo [2,3]-
Wittig rearrangement followed by the departure of the
sulfonyl group and the incorporation of an additional
alkyl group into the molecule, to give secondary E-
homoallyl alcohols 9.13 In this case, the sulfonyl group
not only activates the R-CH2 group toward proton loss
but also departs to furnish a new functionality (a formyl
group in 8) which provides possibilities for further
transformations. However, the reported examples of this
method are limited to the synthesis of secondary alcohols.
[2,3]-Wittig rearrangement has also been applied to the
preparation of â,γ-unsaturated ketones (Scheme 3).
Deprotonation of the allyl ethers of the cyanohydrins 10
effects the rearrangement to the transient â,γ-unsatu-
rated cyanohydrins 11, which are transformed to the
ketones 12.14 However, syntheses of 10 suffer from low
yields as well as the products 12 being contaminated with
the corresponding R,â-unsaturated ketones when R1 and/
or R2 is hydrogen.
In the course of our investigation on the use of
benzotriazole derivatives in organic synthesis,15 we found
that the benzotriazolyl group is both a good anion-
stabilizing group and a good leaving group. These
properties coupled with the ready accessibility of such
derivatives encouraged us to investigate benzotriazole-
mediated [2,3]-Wittig rearrangements and their synthetic
potential. We now report that the benzotriazole deriva-
tives 13 and 19 can be readily lithiated and the resulting
anions undergo facile [2,3]-Wittig rearrangement to
provide, in excellent yields, primary (18), secondary (16),
and tertiary (21) E-homoallyl alcohols and E-â,γ-unsat-
urated ketones (20), respectively, depending on the
reaction conditions and reagents used.
BuOK and alkylated with 1-(chloromethyl)benzotriazole
in DMF at room temperature, the corresponding allyl
(benzotriazol-1-yl)methyl ethers 13a -d were produced
in 63-83% yields (Scheme 4). Allyl 1-(benzotriazol-1-
yl)benzyl ethers 19a -e were prepared in 53-71% yields
from the condensation reactions of benzotriazole, an allyl
alcohol, and an aromatic aldehyde in the presence of
molecular sieves and p-toluenesulfonic acid (Scheme 5).
Ethers 19d and 19e were mixtures of diastereoisomers
which did not need separating for the subsequent trans-
formations. Compounds 13 and 19 were fully character-
ized by their NMR spectra and elemental analyses (or
HRMS).
P r ep a r a tion of Secon d a r y a n d P r im a r y E-Hom o-
a llyl Alcoh ols. Treatment of compounds 13a -d with
2.5 equiv of a nucleophilic alkyl- or aryllithium reagent
at -78 °C provided secondary homoallyl alcohols 16a -f
in good yields (81-87%) (Scheme 4). These transforma-
tions are envisaged to proceed via deprotonation to 14
followed by [2,3]-Wittig rearrangement to form interme-
diates 15, which undergo expulsion of the benzotriazolyl
anion to form aldehydes 17 and subsequent in situ
nucleophilic addition of a second molecule of the lithium
reagent to give the desired products 16. When secondary
allyl ethers 13c,d (R3 * H) were the substrates, the
homoallyl alcohols thus produced (16c-f) existed exclu-
sively in the E configuration as indicated by their olefinic
coupling constants (J ca. 15 Hz). Also noteworthy is the
fact that, in spite of the formation of a quarternary center
Resu lts a n d Discu ssion
P r ep a r a tion of Allyl (Ben zotr ia zol-1-yl)m eth yl
Eth er s 13 an d Allyl 1-(Ben zotr iazol-1-yl)alkyl Eth er s
19. When allylic alcohols were deprotonated with t-
(10) Still, W. C.; McDonald, J . H., III; Collum, D. B.; Mitra, A.
Tetrahedron Lett. 1979, 593.
(11) Kruse, B.; Bruckner, R. Chem. Ber. 1989, 122, 2023.
(12) Broka, C. A.; Shen, T. J . Am. Chem. Soc. 1989, 111, 2981.
(13) Bruckner, R.; Peiseler, B. Tetrahedron Lett. 1988, 29, 5233.
(14) Cazes, B.; J ulia, S. Tetrahedron Lett. 1974, 2077.
(15) For reviews, see: (a) Katritzky, A. R.; Rachwal, S.; Hitchings,
G. J . Tetrahedron 1991, 47, 2683. (b) Katritzky, A. R.; Yang, Z.; Cundy,
D. J . Aldrichimica Acta 1994, 27, 31. (c) Katritzky, A. R.; Lan, X. Chem.
Soc. Rev. 1994, 363. (d) Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis
1994, 445.

Benzotriazole-Mediated [2,3]-Wittig Rearrangement
J . Org. Chem., Vol. 61, No. 12, 1996 4037
Sch em e 5
are complicated by a tendency to undergo prototropic
rearrangement.16
All compounds prepared showed the expected NMR
spectra, and all new compounds were further character-
ized by elemental analyses or HRMS (see Experimental
Section). The NMR results of the crude reaction mixtures
and absence of signals for isomers for 16c-f, 18a ,b, 20c,d
and 21 demonstrated at least 95% stereoselectivity. The
olefinic coupling constants (J around 15 Hz) are indica-
tive of the E configuration of 16c-f, 18a ,b, 20c,d , and
21d (see Experimental Section). In the cases of 20c,d ,
the signals for the olefinic protons were overlapped in
CDCl3. Thus, in order to measure the coupling constants,
1
their H NMR spectra were recorded in CDCl3 and C6D6
and the olefinic coupling constants J are 15.4 and 15.5
Hz, respectively.
Con clu sion
The presently reported facile [2,3]-Wittig rearrange-
ments of allyl (benzotriazolyl)alkyl ethers 13 and 19
enable the easy preparation of primary, secondary, and
tertiary homoallyl alcohols and of â,γ-unsaturated ke-
tones in stereochemically pure form in excellent yields,
all starting from readily available allylic alcohols. The
methodology promises wide generality as well as consid-
erable synthetic utility.
in the rearrangement step, compound 16a was readily
produced in 87% yield when 13a was treated with 2.5
equiv of n-BuLi.
Exp er im en ta l Section
Since the formation of secondary homoallyl alcohols 16
is rationalized by the addition of the lithium reagents to
the aldehyde intermediates 17, it followed that the
presence of hydride instead of nucleophilic lithium re-
agents in the reaction mixtures should produce the
corresponding primary homoallyl alcohols. In accordance
with our expectations, when allyl ethers 13c,d were
treated with 1.2 equiv of LDA and ca. 3 equiv of sodium
borohydride, primary homoallyl alcohols 18a ,b were
formed in yields of 56 and 60% exclusively as the E
isomers (Scheme 4). This approach thus constitutes the
E-selective complement of the Z-selective primary homo-
allyl alcohol syntheses of Still9 and of Bruckner11 (vide
supra).
P r ep a r a tion of Ter tia r y E-Hom oa llyl Alcoh ols
a n d â,γ-Un sa tu r a ted Keton es. In a manner similar
to the reaction sequences 13 f 16, treatment of 19a -d
with 2.5 equiv of n-butyllithium or phenyllithium at -78
°C resulted in the facile formation of tertiary homoallyl
alcohols 21a -d in yields of 72-89% (Scheme 5). Com-
plete E stereocontrol was also achieved in this case, as
exemplified by the formation of 21d (R3 * H). Signifi-
cantly, tertiary homoallyl alcohols of type 21 were
previously inaccessible by Wittig rearrangement meth-
odology.
The formation of tertiary allyl alcohols 21 indicates
ketones 20 as the intermediates. Accordingly, when allyl
ethers 19 were treated with a nonnucleophilic base such
as LDA, the corresponding â,γ-unsaturated ketones
20a -d were isolated in yields of 86-92% via rearrange-
ment and subsequent departure of the benzotriazolyl
group (Scheme 5). This approach to â,γ-unsaturated
ketones has two attractive features: (i) complete stereo-
control was accomplished as illustrated by the exclusive
E configuration of 20c,d and (ii) corresponding isomeric
R,â-unsaturated ketones were not observed in the cases
of 20c and 20d (R1 or/and R2 * H), although many
previously reported syntheses of â,γ-unsaturated ketones
Gen er a l. Melting points were determined with a hot-stage
apparatus and are uncorrected. NMR spectra were recorded
using CDCl3 as the solvent with tetramethylsilane as the
internal standard for 1H (300 MHz) or solvent as the internal
standard for 13C (75 MHz). Tetrahydrofuran was distilled
under nitrogen immediately prior to use from sodium/benzo-
phenone. All reactions with air-sensitive compounds were
carried out under an argon atmosphere. Column chromatog-
raphy was conducted with silica gel 230-400 mesh. 1-(Chloro-
methyl)benzotriazole was prepared according to our previously
reported procedure.15a
Gen er a l P r oced u r e for th e P r ep a r a tion of Allyl (Ben -
zotr ia zol-1-yl)m eth yl Eth er s 13a -d . To a solution of the
appropriate allyl alcohol (36 mmol) in DMF (60 mL) at room
temperature was added t-BuOK (4.04 g, 36 mmol). After 2 h,
1-(chloromethyl)benzotriazole (6.02 g, 36 mmol) was added.
The reaction mixture was stirred at room temperature over-
night. Water (300 mL) was added, and the mixture was
extracted with diethyl ether (4 × 100 mL). The combined
organic extracts were washed with water (3 × 50 mL), dried
over MgSO4, filtered, and evaporated to dryness. The crude
product was subjected to column chromatography (hexanes:
ethyl acetate ) 4:1) to give the pure product.
2-Me t h yl-4-((b e n zot r ia zol-1-yl)m e t h oxy)-2-b u t e n e
(13a ): colorless oil, yield (7.8 g, 79%); 1H NMR δ 1.58 (s, 3H),
1.72 (s, 3H), 4.00 (d, J ) 6.9 Hz, 2H), 5.26 (t, J ) 7.1 Hz, 1H),
6.01 (s, 2H), 7.39-7.44 (m, 1H), 7.51-7.56 (m, 1H), 7.71 (d, J
) 8.3 Hz, 1H), 8.09 (d, J ) 8.3 Hz, 1H); 13C NMR δ 18.0, 25.7,
65.4, 76.1, 110.0, 119.0, 119.9, 124.2, 127.8, 132.8, 139.4, 146.4.
Anal. Calcd for C12H15N3O: C, 66.34; H, 6.96; N, 19.34.
Found: C, 66.63; H, 7.03; N, 19.35.
1-P h e n yl-3-((b e n zot r ia zol-1-yl)m e t h oxy)-1-p r op e n e
(13b): white prisms, mp 76-79 °C, yield (6.0 g, 63%); 1H NMR
δ 4.16 (d, J ) 6.3 Hz, 2H), 6.06 (s, 2H), 6.15 (dt, J ) 15.9 and
6.3 Hz, 1H), 6.60 (d, J ) 15.9 Hz, 1H), 7.23-7.34 (m, 5H),
7.38-7.43 (m, 1H), 7.51-7.56 (m, 1H), 7.71 (d, J ) 8.3 Hz,
1H), 8.08 (d, J ) 8.5 Hz, 1H); 13C NMR δ 69.5, 75.9, 109.9,
120.1, 123.6, 124.3, 126.6, 127.9, 128.0, 128.5, 132.8, 134.3,
(16) Kachinsky, J . L. C.; Salomon, R. G. J . Org. Chem. 1986, 51,
1393 and references cited therein.

4038 J . Org. Chem., Vol. 61, No. 12, 1996
Katritzky et al.
136.2, 146.5. Anal. Calcd for C16H15N3O: C, 72.43; H, 5.70;
N, 15.84. Found: C, 72.09; H, 5.69; N, 15.96.
(dt, J ) 15.4 and 6.4 Hz, 1H), 5.61 (dt, J ) 15.4 and 6.3 Hz,
1H), 7.24-7.34 (m, 5H); 13C NMR δ 13.7, 25.6, 42.7, 73.5, 124.5,
125.8, 127.3, 128.3, 136.5, 144.1; HRMS calcd for C12H16
O
3-((Ben zotr ia zol-1-yl)m eth oxy)-1-octen e (13c): colorless
oil, yield (7.3 g, 78%); 1H NMR δ 0.72 (t, J ) 7.3 Hz, 3H), 0.91-
1.15 (m, 6H), 1.34-1.52 (m, 2H), 3.72-3.79 (m, 1H), 5.27-
5.35 (m, 2H), 5.61-5.73 (m, 1H), 5.95 (d, J ) 11.4 Hz, 1H),
6.06 (d, J ) 11.4 Hz, 1H), 7.39-7.44 (m, 1H), 7.51-7.57 (m,
1H), 7.72 (d, J ) 8.3 Hz, 1H), 8.09 (d, J ) 8.3 Hz, 1H); 13C
NMR δ 13.8, 22.4, 24.6, 31.2, 34.9, 74.4, 79.2, 110.0, 118.9,
120.0, 124.2, 127.7, 132.9, 136.9, 146.4. Anal. Calcd for
C15H21N3O: C, 69.47; H, 8.16; N, 16.20. Found: C, 69.86; H,
8.24; N, 16.40.
3-((Ben zotr ia zol-1-yl)m eth oxy)-1-p en ten e (13d ): color-
less oil, yield (6.5 g, 83%); 1H NMR δ 0.68 (t, J ) 7.4 Hz, 3H),
1.43-1.56 (m, 2H), 3.66-3.73 (m, 1H), 5.27-5.35 (m, 2H),
5.60-5.72 (m, 1H), 6.00 (d, J ) 11.2 Hz, 1H), 6.04 (d, J ) 11.2
Hz, 1H), 7.38-7.44 (m, 1H), 7.51-7.56 (m, 1H), 7.70-7.74 (m,
1H), 8.07-8.10 (m, 1H); 13C NMR δ 9.3, 27.8, 74.3, 80.6, 109.9,
119.0, 119.8, 124.1, 127.6, 132.8, 136.5, 146.2; HRMS calcd
for C12H15N3O 218.1293 (M + 1), found 218.1302.
Gen er a l P r oced u r e for th e P r ep a r a tion of Secon d a r y
Hom oa llyl Alcoh ols 16a -f. To a solution of the appropriate
allyl (benzotriazol-1-yl)methyl ether 13 (1.7 mmol) in THF (100
mL) at -78 °C under argon was added n-BuLi (2.4 mL, 4.3
mmol, 1.8 M in cyclohexane). The mixture was stirred and
allowed to warm to room temperature overnight. Water (50
mL) was added, and the mixture was extracted with diethyl
ether (3 × 50 mL). The combined organic extracts were dried
over MgSO4, filtered, and evaporated to dryness. The crude
product was subjected to column chromatography (hexanes:
ethyl acetate ) 5:1) to give the pure product.
175.1123 (M - 1), found 175.1162.
Gen er a l P r oced u r e for t h e P r ep a r a t ion of P r im a r y
Hom oa llyl Alcoh ols 18a ,b. To a solution of the appropriate
allyl (benzotriazol-1-yl)methyl ether 13 (4 mmol) and NaBH4
(0.3 g, 8 mmol) in THF (100 mL) at -78 °C under argon was
added LDA (6.7 mL, 10 mmol, 1.5 M in cyclohexane). The
mixture was stirred and allowed to warm to room temperature
overnight. Water (50 mL) was added, and the mixture was
extracted with diethyl ether (3 × 50 mL). The combined
organic extracts were dried over MgSO4, filtered, and evapo-
rated to dryness. The crude product was subjected to column
chromatography (hexanes:ethyl acetate ) 4:1) to give the pure
product.
3-Hexen -1-ol (18a ): colorless oil, yield (0.22 g, 56%); 1H
NMR δ 0.99 (t, J ) 7.5 Hz, 3H), 1.68 (br s, 1H), 1.99-2.09 (m,
2H), 2.23-2.30 (m, 2H), 3.63 (t, J ) 6.3 Hz, 2H), 5.39 (dt, J )
15.3 and 8.0 Hz, 1H), 5.61 (dt, J )15.3 and 6.2 Hz, 1H); 13C
NMR 13.7, 25.6, 35.9, 62.0, 124.8, 135.7. The spectral data
for 18a are in agreement with published19 values.
3-Non en -1-ol (18b): colorless oil, yield (0.34 g, 60%); 1H
NMR δ 0.89 (t, J ) 6.7 Hz, 3H), 1.25-1.41 (m, 6H), 1.67 (br s,
1H), 2.00-2.05 (m, 2H), 2.26 (q, J ) 6.6 Hz, 2H), 3.62 (t, J )
6.0 Hz, 2H), 5.38 (dt, J ) 15.3 and 6.8 Hz, 1H), 5.56 (dt, J )
15.3 and 6.6 Hz, 1H); 13C NMR δ 14.0, 22.5, 29.1, 31.4, 32.6,
36.0, 62.0, 125.7, 134.2. The spectral data for 18b are in
agreement with published20 values.
Gen er al P r ocedu r e for th e P r epar ation of Allyl 1-(Ben -
zotr ia zol-1-yl)a lk yl Eth er s 19a -e. To a solution of an allyl
alcohol (20 mmol), an aldehyde (20 mmol), and benzotriazole
(2.6 g, 21.8 mmol) in CH2Cl2 (60 mL) at room temperature were
added p-toluenesulfonic acid (1.9 g, 10 mmol) and molecular
sieves (4 Å, 30 g). After the mixture was stirred at room
temperature for 2 days, the molecular sieves were removed
by filtration and the solvent was evaporated. The residue was
dissolved in diethyl ether (100 mL), and the solution was
washed with an aqueous NaOH solution (60 mL, 5 N). The
aqueous layer was extracted with diethyl ether (3 × 50 mL),
and the combined organic extracts were dried over MgSO4,
filtered, and evaporated to dryness. The crude product was
subjected to column chromatography (hexanes:ethyl acetate
) 20:1) to give the pure product.
3,3-Dim eth yl-1-octen -4-ol (16a ): colorless oil, yield (0.23
g, 87%); 1H NMR δ 0.92 (t, J ) 7.0 Hz, 3H), 1.02 (s, 6H), 1.22-
1.40 (m, 4H), 1.51-1.56 (m, 3H), 3.24-3.27 (m, 1H), 5.03-
5.12 (m, 2H), 5.84 (dd, J ) 17.4 and 11.0 Hz, 1H); 13C NMR δ
14.0, 22.1, 22.7, 23.1, 29.2, 31.1, 41.6, 78.3, 113.1, 145.5; HRMS
calcd for C10H20O 157.1592 (M + 1), found 157.1636.
3-P h en yl-4-p en ten -2-ol (16b): colorless oil, a mixture of
two diastereoisomers (78:22) (signals of minor isomer in
1
brackets), yield (0.22 g, 81%); H NMR δ 1.09 [1.26] (d, J )
6.2 Hz, 3H), 1.98 (d, J ) 2.5 Hz, 1H), 3.16-3.29 (m, 1H), 3.97-
4.04 (m, 1H), 5.12-5.28 (m, 2H), 6.00-6.20 (m, 1H), 7.19-
7.39 (m, 5H); 13C NMR δ 20.6 [20.7], 59.1 [58.9], 70.2 [70.4],
117.9 [116.8], 126.7 [126.9], 127.9 [128.4], 128.6 [128.8], 138.5
[138.4], 141.5 [140.9]; HRMS calcd for C11H14O 163.1123 (M
+ 1), found 163.1162.
1-((Ben zotr iazol-1-yl)(4-m eth ylph en yl)m eth oxy)-3-m eth -
1
yl-2-bu ten e (19a ): colorless oil, yield (4.1 g, 67%); H NMR
7-Tr id ecen -5-ol (16c): colorless oil, yield (0.28 g, 84%); 1H
NMR δ 0.87-0.94 (m, 6H), 1.23-1.46 (m, 12H), 1.69 (br s, 1H),
1.99-2.09 (m, 3H), 2.20-2.28 (m, 1H), 3.55-3.62 (m, 1H), 5.41
(dt, J ) 15.5 and 6.8 Hz, 1H), 5.55 (dt, J ) 15.5 and 6.4 Hz,
1H); 13C NMR δ 14.0, 22.5, 22.7, 27.9, 29.1, 31.4, 32.6, 36.4,
40.7, 70.9, 125.8, 134.7. The spectral data for 16c are in
agreement with published17 values.
δ 1.54 (s, 3H), 1.70 (s, 3H), 2.31 (s, 3H), 3.97-4.03 (m, 1H),
4.07-4.14 (m, 1H), 5.30-5.35 (m, 1H), 7.13 (d, J ) 8.2 Hz,
2H), 7.21 (s, 1H), 7.26-7.36 (m, 5H), 8.03-8.06 (m, 1H); 13C
NMR δ 18.0, 21.1, 25.7, 65.3, 88.4, 111.8, 119.0, 119.7, 124.0,
125.8, 127.2, 129.1, 131.2, 133.6, 138.7, 139.3, 146.9. Anal.
Calcd for C19H21N3O: C, 74.24; H, 6.89; N, 13.67. Found: C,
74.09; H, 6.91; N, 14.06.
4-Decen -2-ol (16d ): colorless oil, yield (0.23 g, 86%); 1H
NMR δ 0.89 (t, J ) 6.9 Hz, 3H), 1.18 (d, J ) 6.2 Hz, 3H), 1.21-
1.41 (m, 6H), 1.84 (s, 1H), 1.98-2.24 (m, 4H), 3.75-3.81 (m,
1H), 5.41 (dt, J ) 15.3 and 6.4 Hz, 1H), 5.54 (dt, J ) 15.3 and
6.4 Hz, 1H); 13C NMR δ 14.0, 22.4, 22.5, 29.1, 31.3, 32.6, 42.5,
67.2, 125.7, 134.6. The spectral data for 16d are in agreement
with published18 values.
1-((Be n zot r ia zol-1-yl)p h e n ylm e t h oxy)-3-m e t h yl-2-
bu ten e (19b): colorless oil, yield (3.6 g, 61%); 1H NMR δ 1.56
(s, 3H), 1.72 (s, 3H), 4.04-4.12 (m, 2H), 5.32-5.35 (m, 1H),
7.25-7.44 (m, 9H), 8.05-8.09 (m, 1H); 13C NMR δ 18.0, 25.8,
65.4, 88.4, 111.8, 119.0, 119.8, 124.1, 126.0, 127.3, 128.5, 128.9,
129.0, 131.2, 136.6, 147.0. Anal. Calcd for C18H19N3O: C,
73.70; H, 6.53; N, 14.32. Found: C, 73.81; H, 6.93; N, 14.28.
1-P h en yl-3-((ben zotr ia zol-1-yl)p h en ylm eth oxy)-1-p r o-
p en e (19c): white solid, mp 74-75 °C, yield (3.5 g, 53%); 1H
NMR δ 4.22-4.25 (m, 2H), 6.23 (dt, J ) 15.9 and 6.0 Hz, 1H),
6.61 (d, J ) 15.9 Hz, 1H), 7.22-7.36 (m, 12H), 7.44-7.48 (m,
2H), 8.04-8.08 (m, 1H); 13C NMR δ 69.4, 88.3, 111.5, 119.8,
123.4, 124.1, 125.9, 126.5, 127.4, 127.9, 128.4, 128.5, 128.9,
131.1, 134.3, 136.0, 136.1, 146.9. Anal. Calcd for C22H19N3O:
C, 77.40; H, 5.61; N, 12.31. Found: C, 77.26; H, 5.63; N, 12.27.
3-((Ben zotr ia zol-1-yl)p h en ylm eth oxy)-1-octen e (19d ):
colorless oil, a mixture of two diastereoisomers (1:1) (signals
of the other isomer in brackets), yield (4.7 g, 71%); 1H NMR δ
1-P h en yl-3-n on en -1-ol (16e): colorless oil, yield (0.31 g,
1
84%); H NMR δ 0.88 (t, J ) 6.9 Hz, 3H), 1.21-1.40 (m, 6H),
1.98-2.05 (m, 2H), 2.10 (d, J ) 3.2 Hz, 1H), 2.35-2.50 (m,
2H), 4.65-4.70 (m, 1H), 5.39 (dt, J ) 15.3 and 6.7 Hz, 1H),
5.57 (dt, J ) 15.3 and 6.7 Hz, 1H), 7.23-7.36 (m, 5H); 13C NMR
δ 14.0, 22.5, 29.1, 31.3, 32.6, 42.8, 73.5, 125.4, 125.8, 127.4,
128.3, 135.2, 144.1; HRMS calcd for C15H22O: 219.1748 (M +
1), found 219.1727.
1-P h en yl-3-h exen -1-ol (16f): colorless oil, yield (0.25 g,
1
85%); H NMR δ 0.97 (t, J ) 7.4 Hz, 3H), 1.99-2.08 (m, 2H),
2.20 (br s, 1H), 2.37-2.46 (m, 2H), 4.63-4.68 (m, 1H), 5.39
(17) D’Auria, M.; De Mico, A.; D’Onofrio, F.; Scettri, A. Synthesis
1985, 988.
(18) Maryanoff, B. E.; Reitz, A. B.; Duhl-Emswiler, B. A. J . Am.
Chem. Soc. 1985, 107, 217.
(19) Barluenga, J .; Alvarez, F.; Concellon, J . M.; Yus, M. Synthesis
1986, 654.
(20) Kocienski, P. J .; Pritchard, M.; Wadman, S. N.; Whitby, R. J .;
Yeates, C. L. J . Chem. Soc., Perkin Trans. 1 1992, 3419.

Benzotriazole-Mediated [2,3]-Wittig Rearrangement
J . Org. Chem., Vol. 61, No. 12, 1996 4039
0.59-1.58 (m, 11H), 3.59-3.67 [4.08-4.12] (m, 1H), 5.01-5.40
(m, 2H), 5.67-5.89 (m, 1H), 7.20-7.46 (m, 8H), 7.79-8.02 (m,
2H); 13C NMR δ 13.7 [13.9], 22.2 [22.5], 24.6 [24.9], 31.1 [31.6],
34.9 [37.0], 73.3 [78.9], 86.2, 111.8, 114.5, 119.6 [119.7], 124.3,
125.9, 127.3, 128.5, 128.8, 128.9, 136.5, 141.1, 146.7. Anal.
Calcd for C21H25N3O: C, 75.19; H, 7.51; N, 12.53. Found: C,
75.04; H, 7.68; N, 12.36.
3-((Ben zotr iazol-1-yl)(4-m eth ylph en yl)m eth oxy)-1-pen -
ten e (19e): colorless oil, a mixture of two diastereomers (5:
1) (signals of minor isomer in brackets), yield (3.7 g, 60%); 1H
NMR δ 0.68 [0.99] (t, J ) 7.4 Hz, 3H), 1.49-1.64 (m, 2H), 2.32
(s, 3H), 3.59-3.66 (m, 1H) [4.02-4.10], 5.36-5.43 (m, 2H),
5.74-5.86 (m, 1H), 7.13-7.30 (m, 2H), 7.31-7.37 (m, 6H),
8.04-8.08 (m, 1H); 13C NMR δ 9.47, 21.1, 28.0 [27.6], 80.2
[82.5], 86.1 [88.6], 111.8, 116.4, 119.7 [119.9], 124.0, 125.8,
127.0 [127.1], 129.1 [129.2], 131.2, 133.7, 136.3 [136.8], 138.6,
146.9. Anal. Calcd for C19H21N3O: C, 74.24; H, 6.89; N, 13.67.
Found: C, 74.37; H, 7.05; N, 13.41.
6H), 2.01-2.08 (m, 2H), 3.68 (d, J ) 5.3 Hz, 2H), 5.57-5.70
(m, 2H), 7.26-7.47 (m, 2H), 7.52-7.57 (m, 1H), 7.94-7.97 (m,
2H); 13C NMR δ 14.0, 22.5, 28.9, 31.3, 32.6, 42.5, 122.1, 128.3,
128.5, 132.9, 135.1, 136.7, 198.6. The spectral data for 20d
are in agreement with published22 values.
Gen er a l P r oced u r e for t h e P r ep a r a t ion of Ter t ia r y
Hom oa llyl Alcoh ols 21a -d . To a solution of the appropriate
allyl 1-(benzotriazol-1-yl)alkyl ether 19 (2.2 mmol) in THF (100
mL) at -78 °C under argon was added n-BuLi (3.7 mL, 5.5
mmol, 1.5 M in cyclohexane). The mixture was stirred and
allowed to warm to room temperature overnight. Water (50
mL) was added, and the mixture was extracted with diethyl
ether (3 × 50 mL). The combined organic extracts were dried
over MgSO4, filtered, and evaporated to dryness. The crude
product was subjected to column chromatography (hexanes:
ethyl acetate ) 6:1) to give the pure product.
3,3-Dim eth yl-4-(4-m eth ylph en yl)-1-octen -4-ol (21a): col-
1
orless oil, yield (0.48 g, 89%); H NMR δ 0.83 (t, J )7.1 Hz,
Gen er a l P r oced u r e for th e P r ep a r a tion of â,γ-Un sa t-
u r a ted Keton es 20a -d . To a solution of the appropriate allyl
1-(benzotriazol-1-yl)alkyl ether 19 (2.6 mmol) in THF (100 mL)
at -78 °C under argon was added LDA (2.1 mL, 3.1 mmol,
1.5 M in cyclohexane). The mixture was stirred and allowed
to warm to room temperature overnight. Water (50 mL) was
added, and the mixture was extracted with diethyl ether (3 ×
50 mL). The combined organic extracts were dried over
MgSO4, filtered, and evaporated to dryness. The crude product
was subjected to column chromatography (hexanes:ethyl ace-
tate ) 10:1) to give the pure product.
3H), 0.86-0.92 (m, 1H), 0.95 (s, 3H), 1.01 (s, 3H), 1.13-1.32
(m, 3H), 1.68-1.78 (m, 1H), 1.86 (s, 1H), 2.09-2.19 (m, 1H),
2.34 (s, 3H), 5.02 (d, J ) 17.6 Hz, 1H), 5.09 (d, J ) 11.0 Hz,
1H), 5.99 (dt, J ) 17.6 and 11.0 Hz, 1H), 7.11 (d, J ) 8.4 Hz,
2H), 7.25 (d, J ) 8.4 Hz, 2H); 13C NMR δ 14.1, 20.9, 22.7, 23.3,
26.0, 35.2, 44.9, 80.0, 113.6, 127.5, 127.8, 135.7, 139.6, 145.5;
HRMS calcd for C17H26O 247.2062 (M + 1), found 247.2079.
1,1-Dip h en yl-2,2-d im eth yl-3-bu ten -1-ol (21b): colorless
1
oil, yield (0.40 g, 72%); H NMR δ 1.20 (s, 6H), 2.48 (s, 1H),
5.15 (d, J ) 17.6 Hz, 1H), 5.18 (d, J ) 10.9 Hz, 1H), 6.20 (dd,
J ) 17.6 and 10.9 Hz, 1H), 7.18-7.29 (m, 6H), 7.54-7.58 (m,
4H); 13C NMR δ 24.3, 45.4, 81.6, 112.6, 126.6, 127.2, 128.2,
1-P h en yl-2,2-d im eth yl-3-bu ten -1-on e (20a ): colorless oil,
1
yield (0.41 g, 91%); H NMR δ 1.40 (s, 6H), 5.22 (d, J ) 10.6
128.4, 130.0, 132.4, 145.5, 146.3; HRMS calcd for C18H20
O
Hz, 1H), 5.24 (d, J ) 17.6 Hz, 1H), 6.20 (dd, J ) 17.6 and 10.7
Hz, 1H), 7.35-7.47 (m, 3H), 7.87-7.90 (m, 2H); 13C NMR δ
26.0, 50.1, 114.0, 127.9, 129.2, 131.6, 137.1, 143.8, 204.6. The
spectral data for 20a are in agreement with published16 values.
1-(4-Meth ylp h en yl)-2,2-d im eth yl-3-bu ten -1-on e (20b):
253.1592 (M + 1), found 253.1588.
3,4-Dip h en yl-1-octen -4-ol (21c): colorless oil, yield (0.51
g, 83%); 1H NMR δ 0.76 (t, J ) 6.9 Hz, 3H), 0.85-0.88 (m,
1H), 1.15-1.25 (m, 3H), 1.86-1.91 (m, 2H), 2.05 (s, 1H), 3.56
(d, J ) 9.9 Hz, 1H), 5.09-5.19 (m, 2H), 6.19-6.31 (m, 1H),
6.82-6.85 (m, 2H), 7.03-7.26 (m, 8H); 13C NMR δ 14.0, 23.1,
25.7, 39.7, 62.2, 78.4, 117.9, 126.1, 126.2, 126.4, 127.4, 127.7,
129.3, 137.4, 140.1, 144.1. Anal. Calcd for C20H24O: C, 85.66;
H, 8.63. Found: C, 85.56; H, 8.84.
1,1-Dip h en yl-3-n on en -1-ol (21d ): colorless oil, yield (0.56
g, 86%); 1H NMR δ 0.79 (t, J ) 6.8 Hz, 3H), 1.09-1.28 (m,
6H), 1.85-1.93 (m, 2H), 2.58 (s, 1H), 2.93 (d, J ) 7.1 Hz, 2H),
5.18 (dt, J ) 15.3 and 7.2 Hz, 1H), 5.59 (dt, J ) 15.3 and 6.8
Hz, 1H), 7.11-7.26 (m, 6H), 7.35-7.39 (m, 4H); 13C NMR δ
14.0, 22.4, 29.0, 31.3, 32.6, 45.6, 76.8, 124.2, 126.0, 126.7, 128.1,
137.6, 146.7. Anal. Calcd for C21H26O: C, 85.67; H, 8.90.
Found: C, 85.42; H, 9.09.
1
colorless oil, yield (0.42 g, 86%); H NMR δ 1.40 (s, 6H), 2.38
(s, 3H), 5.18 (d, J ) 10.7 Hz, 1H), 5.21 (d, J ) 17.6 Hz, 1H),
6.20 (dd, J ) 17.6 and 10.6 Hz, 1H), 7.18 (d, J ) 8.2 Hz, 2H),
7.83 (d, J ) 8.2 Hz, 2H); 13C NMR δ 21.4, 26.1, 50.0, 113.7,
128.5, 129.6, 134.1, 142.2, 144.1, 203.8. The spectral data for
20b are in agreement with published21 values.
1-(4-Meth ylp h en yl)-3-h exen -1-on e (20c): colorless oil,
yield (0.52 g, 89%); 1H NMR δ 0.98 (t, J ) 7.4 Hz, 3H), 2.04-
2.09 (m, 2H), 2.39 (s, 3H), 3.64 (dd, J ) 5.1 and 1.1 Hz, 2H),
5.63-5.67 (m, 2H), 7.24 (d, J ) 8.1 Hz, 2H), 7.86 (d, J ) 8.1
Hz, 2H); 13C NMR δ 13.5, 21.6, 25.6, 42.4, 121.5, 128.4, 129.2,
134.2, 136.3, 143.7, 198.3; HRMS calcd for C13H16O 189.1279
(M + 1), found 189.1276.
1-P h en yl-3-n on en -1-on e (20d ): colorless oil, yield (0.51
J O960019D
g, 92%); 1H NMR δ 0.87 (t, J ) 6.7 Hz, 3H), 1.23-1.39 (m,
(21) Marceau, P.; Gautreau, L.; Beguin, F.; Guillaumet, G. J .
Organomet. Chem. 1991, 403, 21.
(22) Pohmakotr, M.; Seebach, D. Angew. Chem. 1977, 89, 333; Chem.
Abstr. 1977, 87, 22666v.