Convenient Synthesis of Functionalized Dialkyl Ketones and Alkanoylsilanes: 1-(Benzotriazol-1-yl)-1-phenoxyalkanes as Alkanoyl Anion Equivalents

Article abstract of DOI:10.1021/jo960830o

(Benzotriazol-1-yl)-1-phenoxyalkanes 10, prepared by two-step transformations of the corresponding aldehydes, are readily deprotonated at the methine group by BuLi.Subsequent reactions with alkyl halides, aldehydes, ketones, and imines yield the corresponding substituted derivatives that undergo hydrolysis under acidic conditions to afford the expected functionalized ketones 13, 15, 17, 19, 21, 24 and 25.Two successive lithiations of (benzotriazolyl)phenoxymethane, each followed by reaction with a trialkylsilyl chloride, alkyl halide, aldehyde, or ketone, generate similar intermediates 27, 39, 31, 33, and 36.Subsequent hydrolyses of 27, 29, 31, 33, and 36 yield the functionalized ketones 28, 30, and 32 and the alkanoylsilanes 34 and 37 in good yields.

Full text of DOI:10.1021/jo960830o

J . Org. Chem. 1996, 61, 7551-7557
7551
Con ven ien t Syn th eses of F u n ction a lized Dia lk yl Keton es a n d
Alk a n oylsila n es: 1-(Ben zotr ia zol-1-yl)-1-p h en oxya lk a n es a s
Alk a n oyl An ion Equ iva len ts
Alan R. Katritzky,* Hengyuan Lang, Zuoquan Wang, and Zhu Lie
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received May 6, 1996X
(Benzotriazol-1-yl)-1-phenoxyalkanes 10, prepared by two-step transformations of the corresponding
aldehydes, are readily deprotonated at the methine group by BuLi. Subsequent reactions with
alkyl halides, aldehydes, ketones, and imines yield the corresponding substituted derivatives that
undergo hydrolysis under acidic conditions to afford the expected functionalized ketones 13, 15,
17, 19, 21, 24, and 25. Two successive lithiations of (benzotriazolyl)phenoxymethane, each followed
by reaction with a trialkylsilyl chloride, alkyl halide, aldehyde, or ketone, generate similar
intermediates 27, 29, 31, 33, and 36. Subsequent hydrolyses of 27, 29, 31, 33, and 36 yield the
functionalized ketones 28, 30, and 32 and the alkanoylsilanes 34 and 37 in good yields.
In tr od u ction
We have recently demonstrated that alkenyl- (1a ),
alkynyl- (1b), and aryl- (including heteroaryl-)substituted
(1c) N-(ethoxymethyl)benzotriazoles are versatile acyl
anion equivalents, which can be used advantageously for
the preparation of a wide variety of functionalized
alkenyl,1,2 alkynyl,3 aryl,4 and heteroaryl4 ketones and
alkenoyl-, alkynoyl-, aroyl-, and heteroaroylsilanes.5 The
benzotriazole-stabilized carbanions derived from 1a -c all
share the following features: convenient availability of
starting materials, adequate reactivity toward various
electrophiles including alkyl halides, aldehydes, ketones,
and imines, and mild conditions for the hydrolysis of the
intermediates thus produced. However, this methodology
is not immediately applicable to alkyl-substituted N-
(ethoxymethyl)benzotriazoles (1d ) because the deproto-
nation of 1d is difficult; this can be understood as the
vinyl, ethynyl, and aryl groups of 1a -c obviously play
an important role in the stabilization of their correspond-
ing anions. Previous work in our group has demon-
strated that (carbazol-9-yl)(benzotriazol-1-yl)methane is
an efficient acyl anion equivalent,6 but its relatively large
molecular weight (and occasional difficult reactions with
sterically hindered electrophiles, such as triisopropylsilyl
chloride) makes a smaller analog desirable. We now find
that use of phenoxy compounds of type 10 in place of the
ethoxy or carbazolyl analogs allows ready deprotonation
to 11 and provides a convenient access to alkyl-substi-
tuted functionalized ketones, including bulky trialkylsilyl
(R3Si-)-substituted alkanoylsilanes that were difficult to
prepare by previous methods.
general reviews see refs 8 and 9). The preparation of
acyl anion precursors has commonly been carried out by
one of two alternative strategies: (i) lithiation of a formyl
anion equivalent such as 2, 3, 4, or 7 (R ) H) and
subsequent alkylation with RX to give 2, 3, 4, or 7 (R *
H). Use of such species as acyl anion equivalents is thus
essentially a double-lithiation process, which provides
flexibility for the introduction of two different substitu-
ents. (ii) An alternative strategy is the generation of acyl
anion equivalents such as 2-8 directly from the corre-
sponding aldehydes or their equivalents, which allows
the conversions of available aldehydes into substituted
ketones. In the present work, we have successfully
utilized both of these strategies to provide novel acyl
anion equivalents 10.
Resu lts a n d Discu ssion
The use of acyl anion equivalents has proven to be a
powerful strategy in the synthesis of many carbonyl
compounds, as referenced in previous papers6,7 (for more
Con ver sion of Alip h a tic Ald eh yd es in to Dia lk yl
Keton es a n d r-Hyd r oxy a n d r-Am in o F u n ction a l-
ized Keton es. The intermediates 1-(benzotriazol-1-yl)-
1-phenoxyalkanes 10 were prepared in two-step pro-
cesses. Previously reported reactions of aldehydes,
benzotriazole, and thionyl chloride in benzene yielded
1-(benzotriazol-1-yl)-1-chloroalkanes 9.10 We have now
replaced the chloro atom in the R-(chloroalkyl)benzotri-
X Abstract published in Advance ACS Abstracts, September 15, 1996.
(1) Katritzky, A. R.; J iang, J . J . Org. Chem. 1995, 60, 6.
(2) Katritzky, A. R.; Zhang, G.; J iang, J . J . Org. Chem. 1995, 60,
7589.
(3) Katritzky, A. R.; Lang, H. J . Org. Chem. 1995, 60, 7612.
(4) Katritzky, A. R.; Lang, H.; Wang, Z.; Zhang, Z.; Song, H. J . Org.
Chem. 1995, 60, 7619.
(5) Katritzky, A. R.; Wang, Z.; Lang, H. Organometallics 1995, 15,
486.
(6) Katritzky, A. R.; Yang, Z.; Lam, J . N. J . Org. Chem. 1991, 56,
6917.
(8) Ager, D. J . In Umpoled Synthons: A Survey of Source and Uses
in Synthesis; Hase, T. A., Ed.; J ohn-Wiley & Sons: New York, 1987; p
19.
(9) Martin, S. F. Synthesis 1979, 633.
(7) Katritzky, A. R.; Yang, Z.; Lam, J . N. J . Org. Chem. 1991, 56,
2143.
(10) Katritzky, A. R.; Kuzmierkiewicz, W.; Rachwal, B.; Rachwal,
S.; Thomso, J . J . Chem. Soc., Perkin Trans. 1, 1987, 811.
S0022-3263(96)00830-4 CCC: $12.00 © 1996 American Chemical Society

7552 J . Org. Chem., Vol. 61, No. 21, 1996
Katritzky et al.
Sch em e 1
subject to the availability of the alcohols. Preparations
of dialkyl ketones (RCOR′) from two alkyl halides (RX
and R′X) were effected via conversion of one alkyl halide
into an aldehyde (RCHO) by treatment with disodium
tetracarbonylferrate11,12 or with the selenium compound
13
Me3SiCH(Li)SePh followed by H2O2 and subsequent
reaction with the Grignard reagent from another R′X and
final oxidation of the hydroxy group. Use of a previous
acyl anion equivalent strategy has been another common
approach.8
Reactions of anion 11a with 4-tolualdehyde for a few
minutes at -78 °C generated intermediate 14b in 80%
yield. Unlike the preparations of 12a -d , the reaction
11a f 14b was complete at -78 °C after 10 min without
raising the temperature. The NMR spectra of 14b
indicated the presence of two diastereomers in a ratio of
4:1. Hydrolysis of 14b under the same conditions as
described for 12a -d provided 15b in 96% yield. The
structure of 15b was confirmed by NMR spectra and
CHN analysis.
Reactions of 11a with benzaldehyde or benzophenone
and of anion 11b with N-benzylideneaniline as electro-
philes were carried out without isolation of intermediates
14a , 16, and 18, hydrolysis of which gave the correspond-
ing R-hydroxy- and R-amino-substituted ketones 15a , 17
and 19 in 65-74% yields.
R-Hydroxy ketones of types 15 and 17 have been
prepared from 1,3-dithiane acyl anion equivalents (2).8
However, as discussed in our recent papers,4,6 hydrolyses
of 2 require the irreversible removal of the dithiol, which
is still most often accomplished by complex formation
with heavy-metal salts (HgO and HgCl2). Other routes
to R-hydroxy ketones of types 15 and 17 include reduction
of R-dicarbonyl ketones,14 oxidation of 1,2-dihydroxy
compounds,15 oxidation of alkenes,16 thiazolium-catalyzed
dimerization of aldehydes,17 and acyloin condensation.18
However, these methods are frequently restricted to
starting materials of appropriate symmetry and require
careful control of the reaction conditions to avoid mix-
tures and overreduced or overoxidized products. R-Amino
ketones of type 19 were previously prepared by reactions
of R-chloro,19 R-bromo,20 or R-hydroxy ketones21 with an
amine. An alternative method for the preparation of
compounds of type 19 is condensation of 1,2-dicarbonyl
compounds with an amine followed by reduction.21,22 All
of these routes to compounds 19 are subject to the
availability of the starting materials; for example, the
direct halogenation of many ketones occurs on both sides
of the carbonyl group. No previous report has been found
on the preparation of an alkyl R-aminoalkyl ketone by
an acyl anion equivalent approach.
azoles by phenoxide to give 1-(benzotriazol-1-yl)-1-phe-
noxyalkanes 10a ,b in 75% and 82% yields, respectively.
Compounds 10a ,b are stable to storage at ambient
temperature without special precautions.
Treatment of compound 10a with 1 equiv of butyl-
lithium at -78 °C for 2-5 min resulted in the formation
of anion 11a (Scheme 1). Subsequent reaction with (3-
bromopropyl)benzene at -78 °C for a few minutes and
then at room temperature for 10 min gave intermediate
12d in 90% yield. The structure of 12d was confirmed
spectrally and by CHN analysis: 13C NMR spectra clearly
indicated that the methine carbon of 10a was shifted
downfield due to the introduction of the Ph(CH2)3 sub-
stituent. Hydrolysis of 12d in refluxing aqueous ethanol
(50%) containing 5% sulfuric acid for 10 min afforded 13d
in 96% yield. NMR spectra of 13d showed the presence
of a carbonyl group and the disappearance of the benzo-
triazolyl and phenoxy groups.
The unsymmetric dialkyl ketones 13a -c were simi-
larly prepared in 64-90% overall yields (Table 1) without
isolation of the corresponding intermediates 12a -c.
Compared to our previous BtCHAOEt (1a -c) cases,1-5
in which the hydrolyses were carried out with a dilute
acid (HCl, H2SO4, or oxalic acid) solution at room tem-
perature, the hydrolyses of 13a -d require stronger
conditions due to the lack of the activation by a vinyl,
alkynyl, or aryl group. All these reactions, including the
alkylations and hydrolyses, were monitored by TLC until
the starting materials were completely consumed. The
benzotriazole and phenol generated by hydrolysis were
easily removed by washing the organic extracts with
2N aqueous sodium hydroxide during workup.
(11) Cainelli, G.; Manescalchi, F.; Umani-Ronchi, A.; Panunzio, M.
J . Org. Chem. 1978, 43, 1598.
(12) Cooke, M. P., J r. J . Am. Chem. Soc. 1970, 92, 6080.
(13) Sachdev, K.; Sachdev, H. S. Tetrahedron Lett. 1976, 4223.
(14) Mori, T.; Nakahara, T.; Nozaki, H. Can. J . Chem. 1969, 47,
3266.
(15) Minami, I.; Yamada, M.; Tsuji, J . Tetrahedron Lett. 1986, 27,
1805.
(16) Sakata, Y.; Katayama, Y.; Ishii, Y. Chem. Lett. 1992, 671.
(17) Hassner, A.; Lokanatha Rai, K. M. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York,
1991; Vol. 6, p 541.
(18) Snell, J . M.; McElvain, S. M. Organic Syntheses; Wiley: New
York, 1943; Collect. Vol. II, p 114.
(19) Campaigne, E.; Lake, R. D. J . Org. Chem. 1959, 24, 478.
(20) Vaughan, J . R., J r., Blodinger, J . J . Am. Chem. Soc. 1955, 77,
5757.
(21) Heinzelman, R. V.; Aspergren, B. D. J . Am. Chem. Soc. 1953,
75, 3409.
(22) Armand, J .; Boulares, L. Bull. Soc. Chim. Fr. 1975, 366.
Dialkyl ketones are usually prepared by oxidation of
the corresponding alcohols. However, this route is

Syntheses of Dialkyl Ketones and Alkanoylsilanes
J . Org. Chem., Vol. 61, No. 21, 1996 7553
Ta ble 1. P r ep a r a tion of Keton es 13a -d , 15a ,b, 17, 19, 21, 24, 25, 28a ,b, 30a ,b, a n d 32 a n d Alk a n oylsila n es 34a -g a n d 37
calcd/found
compd
R
R1
EtBr
R2
yield (%)
mp (°C)
C
H (or HR MS)
13a
13b
13c
13d
15a
15b
17
19
21
24
25
28a
28b
30a
30b
32
34a
34b
34c
34d
34e
34f
34g
37
n-C11H23
n-C11H23
n-C5H11
n-C5H11
n-C5H11
n-C5H11
88
90
81
80a
65
76a
76
74
44a
33
23
97
80
52a
43a
41
84a
82
96
85
71
56
46
66
oilb
oilc
oild
oil
oil
oil
BuBr
n-C8H17
Ph(CH2)3
Ph
82.52/82.54
75.69/75.46
76.33/76.07
10.16/10.47
8.80/9.20
9.15/9.43
4-Me-C6H4
oil
283.1620/283.1633
366.2797/366.2740
50-51
oile
oil
309.1854/309.1897
309.1854/309.1859
oil
n-C8H17
n-C8H17
PhCH2
Me
n-C8H17
48-50f
45-47g
92-93h
oil
n-C10H21
4-Me-C6H4
CH(CH2)5
69.19/68.79
10.33/10.16
11.19/11.49
12.22/12.21
8.38/8.39
9.98/10.18
6.37/6.45
12.35/12.67
12.57/12.68
12.22/12.44
9.15/9.40
oil
oil
oil
oil
oil
oil
oil
oil
72.67/72.82
67.22/67.05
68.69/68.39
73.22/73.15
79.70/79.94
68.35/68.22
70.24/70.04
67.22/67.00
60.56/60.49
PhCH2
n-C8H17
n-C7H15
Et
Me
Me
Ph
Ph
n-C8H17
t-Bu
i-Pr
Me
Me
Me
Ph
Me
Me
i-Pr
Et
n-C8H17
Et
oil
a
b
d
Overall yields based on the starting materials 10a ,b or 26. Lit.30 bp10 148 °C. c Lit.31 mp 32-34 °C. Lit.32 bp12 147-148 °C. e Lit.33
f Lit.34 mp 53 °C. Lit.35 mp 47-48.5 °C. Lit.6 mp 90-91 °C.
g
h
Sch em e 2
Con ver sion of Alip h a tic Ald eh yd es in to 1,4-Di-
ca r bon yl Com p ou n d s. When anion 11a was reacted
with 2-cyclohexenone, it gave exclusively the γ-product
20 which was isolated in 48% yield. No 1,2-addition
product was detected. The 13C NMR of the crude
products showed the carbonyl signals as expected for
product 21. Hydrolysis of 20 under conditions similar
to those in the previous cases afforded the expected
ketone 21 in 90% yield. The structures for the interme-
1
diate 20 and the final product 21 were confirmed by H
and 13C NMR spectroscopy. 13C NMR spectra show two
characteristic carbonyl signals at 209.8 and 210.5 ppm
for 21.
However, when trans-chalcone was used as electrophile
to react with anion 11a , both the R-alkylated 23 and the
γ-alkylated products 22 were generated. The crude
mixture was directly subjected to hydrolyses to afford the
1,4-dicarbonyl ketone 24 and R-hydroxy ketone 25 in 33%
and 23% overall yields, respectively (Scheme 2). The loss
of regioselectivity is probably due to the fact that the
γ-position of trans-chalcone is sterically hindered, com-
pared with 2-cyclohexenone.
Phenyl thioacetals 3 have been used for the synthesis
of 1,4-diketones23 by conversion of their lithiated species
to copper reagents and subsequent reaction with R,â-
unsaturated ketones. Previous work in our group re-
ported the preparation of compounds of type 21 and 24
by using (carbazol-9-yl)(benzotriazol-1-yl)alkanes as acyl
anion equivalents.6 As stated earlier, the relatively high
molecular weight of this compound is its major disad-
vantage.
been used in our group25 as a one-carbon homologation
reagent for the conversion of aldehydes to R-acetoxy-
methyl ketones.
We have now found that 26 can also be used as the
substrate in the double-lithiation technique with consid-
erable flexibility. Successive treatment of (benzotriazol-
1-yl)phenoxymethane 26 with 1 equiv of BuLi, followed
by 1 equiv of benzyl bromide, then another equivalent of
BuLi, and finally with p-tolualdehyde gave the interme-
diate 29a , which was isolated in 64% yield. Hydrolysis
of 29a afforded the expected ketone 30a in 81% yield.
The intermediate 29b and ketone 30b were similarly
prepared in 45% and 95% yields, respectively. The
structures of 29a ,b and 30a ,b were fully supported by
NMR spectra and elemental analyses.
F or m a tion of Dia lk yl Keton es a n d r-Hyd r oxy
F u n ction a lized Alip h a tic Keton es by th e Dou ble-
Lith iation Tech n iqu e. (Benzotriazol-1-yl)phenoxymeth-
ane 26 was readily prepared in 87% yield from reaction
of 1-(chloromethyl)benzotriazole with phenoxide ion ac-
cording to the literature.24 Compound 26 has previously
(24) Katritzky, A. R.; Rachwal, S.; Caster, K. C.; Mahni, F.; Law,
K. W.; Rubio, O. J . Chem. Soc., Perkin Trans. 1 1987, 781.
(25) Katritzky, A. R.; Yang, Z.; Moutou, J .-L. Tetrahedron Lett. 1995,
36, 841.
(23) Mukaiyama, T.; Narasaka, K.; Furusato, M. J . Am. Chem. Soc.
1972, 94, 8641.

7554 J . Org. Chem., Vol. 61, No. 21, 1996
Katritzky et al.
Sch em e 3
Sch em e 4
Compounds 28a ,b and 32 were similarly prepared in
52-97% overall yields (Table 1) from 26 by treatment
with the reagents given in Scheme 3 without isolation of
the intermediates 27a ,b and 31. In this approach, if two
identical electrophiles are used, we can easily get the
symmetrical ketones (e.g., 28a ); if two different electro-
philes are used, unsymmetrical ketones (28b) are readily
prepared in high yields. A variety of R-hydroxy ketones
of types 30 and 32 could thus easily be produced from
starting material 26.
P r ep a r a tion of Alk a n oylsila n es. When a trialkyl-
silyl chloride or alkyl bromide was used as one of the
electrophiles, double lithiation of compound 26 provided
various bulky trialkylsilyl-substituted (i-Pr3Si, Ph3Si, and
t-BuMe2Si, etc.) alkanoylsilanes 34a -h in 46-96% yields
(Table 1). We have carried out the reaction sequence by
both (i) adding the alkyl halide first and then introducing
the trialkylsilyl group to give 34a and (ii) using the
reverse order to give 34b-h (Scheme 4). Both ap-
proaches gave satisfactory results, and it appears to make
little difference as to which electrophile (RX or R3SiCl)
is first introduced.
In the first approach, successive treatment of (benzo-
triazol-1-yl)phenoxymethane 26 with 1 equiv of BuLi
followed by quenching with benzyl bromide then with
another 1 equiv of BuLi and lastly with trimethylsilyl
chloride gave the intermediate 33a in 90% yield. Sub-
sequent hydrolysis of 33a afforded the expected ketone
34a in 93% yield (Scheme 4).
In the second strategy, the trialkylsilyl chloride was
introduced into the molecule prior to the alkyl group.
Compounds 34b-g were prepared in 46-96% yields
without isolation of the intermediates 33b-g. The
relatively low yields for 34f,g can be attributed to the
steric hindrance of the electrophiles used [(t-Bu)Me2SiCl
and (i-Pr)3SiCl].
with cyclohexenone gave the intermediate 36, which was
then subjected to in situ hydrolysis to afford the expected
ketone 37 in 66% overall yield. In the preparation of
these alkanoylsilanes 34a -g and 37, the hydrolyses were
accomplished under milder conditions than used above
for the ketones: the intermediate 33a -h and 36 were
refluxed in aqueous THF/acetone containing 1% of 4 N
dilute sulfuric acid. Structures were all confirmed by 1H,
13C NMR spectra and for novel compounds by elemental
analyses. The known compounds have been compared
with literature data. 13C NMR clearly shows the carbonyl
carbon resonance in the range of 243.1-248.3 ppm, which
is typical for acylsilanes.
Previous preparations of alkanoylsilanes have mostly
been restricted to examples with simple trialkylsilyl
group (e.g., Me3Si) substituted compounds, and rarely are
they extended to cases of bulky trialkylsilyl (R3Si-)
substituents. Lipshutz et al.26 recently reported a novel
route to the triisopropylacylsilanes of the type NuCH2-
i
COSiPr3 in overall yields of 50-80% via a two-step
procedure: nucleophilic reaction with triisopropylsilyl-
ethylene oxide and subsequent oxidation of the hydroxy
group. For comparison, Lipshutz26 also utilized the
“dithiane method”, first reported by Corey27 and Brook28
in 1967 to synthesize the butyl triisopropylsilyl ketone
in 32% yield. No previous report has been found of γ-oxo
acylsilanes of type 37: our method appears to be clearly
more general than earlier approaches.
Com p a r ison of 1-(Ben zotr ia zol-1-yl)-1-p h en oxy-
a lk a n es w ith Th eir Eth oxy An a logs. As mentioned
We have also found that when trimethylsilyl chloride
and cyclohexenone were used as electrophiles, a double-
(lithiation + electrophile) sequence provided γ-oxo al-
kanoylsilane 37 in good yield. Thus, successive treat-
ment of (benzotriazol-1-yl)phenoxymethane 26 with 1
equiv of BuLi followed by quenching with trimethylsilyl
chloride and then with another 1 equiv of BuLi and lastly
(26) Lipshutz, B. H.; Lindsley, C.; Susfalk, R.; Gross, T. Tetrahedron
Lett. 1994, 35, 8999.
(27) Corey, E. J .; Seebach, D.; Freedman, R. J . Am. Chem. Soc. 1967,
89, 434.
(28) Brook, A. G.; Duff, J . M.; J ones, P. F.; Davis, N. R. J . Am. Chem.
Soc. 1967, 89, 431.

Syntheses of Dialkyl Ketones and Alkanoylsilanes
J . Org. Chem., Vol. 61, No. 21, 1996 7555
71.1, 110.4, 120.4, 124.6, 128.0, 131.4, 146.6; HRMS calcd for
C18H28N3Cl 322.2050 (M + 1), found 322.2067.
earlier, 1-(benzotriazol-1-yl)-1-ethoxyalkanes (1d ) do not
undergo the easy deprotonation analogous to that which
allows 1a -c to be used as acyl anion synthons. However,
as now demonstrated, replacement of the ethoxy group
in the molecule of 1d by a phenoxy group to give 10
allows deprotonation to proceed smoothly. The lower
mesomeric electron-donor power of the phenoxy group
combined with its larger electron-withdrawing inductive
effect as compared to an ethoxy group evidently makes
the methine proton of 10 more acidic than that of 1d . A
significant difference between the behavior of the phe-
noxy and an alkoxy group has also been observed by
Wedler et. al.29 in the Darzens reaction of phenyl esters
of R-chlorocarboxylic acids with carbonyl compounds:
whereas condensation of aldehydes or ketones with alkyl
esters of R-chlorocarboxylic acids in the presence of a base
generates R-chloro-â-hydroxy esters and R,â-epoxy esters,
use of phenyl esters instead of alkyl esters led to R-chloro-
â-lactones.
Gen er a l P r oced u r e for th e P r ep a r a tion of 10a ,b.
Powdered sodium hydroxide (3.2 g, 80 mmol) was added to a
solution of phenol (3.74 g, 40 mmol) in DMSO (20 mL). The
suspension was stirred for 30 min, and the appropriate
1-(benzotriazol-1-yl)-1-chloroalkane 9a or 9b (40 mmol) was
added. The mixture was heated at 50-60 °C for 1 h and was
poured onto ca. 200 g of ice-water with stirring. The solution
was extracted with diethyl ether (3 × 100 mL) and washed
with NaOH solution (2 N, 100 mL) and water (3 × 150 mL).
Evaporation of the solvent gave the crude product, which was
chromatographed on silica gel (hexane/EtOAc 20:1).
1-(Ben zotr ia zol-1-yl)-1-p h en oxyh exa n e (10a ) was ob-
tained as a colorless oil: yield 75%; 1H NMR δ 0.86 (t, 3 H, J
) 6.8 Hz), 1.20-1.40 (m, 4 H), 1.45-1.60 (m, 2 H), 2.25-2.38
(m, 1 H), 2.43-2.58 (m, 1 H), 6.80-7.00 (m, 4 H), 7.17 (t, 2 H,
J ) 8.1 Hz), 7.32 (t, 1 H, J ) 8.4 Hz), 7.44 (t, 1 H, J ) 7.2 Hz),
7.82 (d, 1 H, J ) 8.1 Hz), 8.03 (d, 1 H, J ) 8.4 Hz); 13C NMR
δ 13.7, 22.3, 24.3, 30.9, 34.7, 88.2, 111.0, 111.1, 116.1, 120.0,
122.8, 124.2, 127.6, 129.6, 146.6, 156.1. Anal. Calcd for
C18H21N3O: C, 73.18; H, 7.17; N, 14.23. Found: C, 73.23; H,
7.38; N, 14.61.
1-(Ben zotr ia zol-1-yl)-1-p h en oxyd od eca n e (10b) was ob-
tained as a colorless oil: yield 82%; 1H NMR δ 0.88 (t, 3 H, J
) 6.6 Hz), 1.10-1.61 (m, 18 H), 2.22-2.40 (m, 1 H), 2.42-
2.59 (m, 1 H), 6.80-7.08 (m, 4 H), 7.13-7.26 (m, 2 H), 7.34 (t,
1 H, J ) 7.7 Hz), 7.45 (t, 1 H, J ) 7.7 hz), 7.82 (d, 1 H, J ) 8.4
Hz), 8.04 (d, 1 H, J ) 8.4 Hz); 13C NMR δ 14.1, 22.6, 24.7,
28.8, 29.3, 29.4, 29.5, 31.8, 34.8, 88.3, 111.2, 116.2, 120.1, 122.8,
124.2, 127.6, 129.6, 131.1, 146.7, 156.2. Anal. Calcd for
C24H33N3O: C, 75.95; H, 8.76; N, 11.07. Found: C, 75.95; H,
8.98; N, 10.94.
Con clu sion s
Novel acyl anion equivalents, 1-(benzotriazol-1-yl)-1-
phenoxyalkanes, have been developed for the generation
of functionalized alkyl ketones and bulky trialkylsilyl (R3-
Si-)-substituted alkanoylsilanes. The simplicity and
generality of the procedures, coupled with the convenient
availability of the starting materials, give these methods
considerable potential importance in organic synthesis.
Gen er a l P r oced u r e for th e P r ep a r a tion of In ter m ed i-
a tes 12d , 14b, a n d 20, a n d Keton es 13d , 15b, a n d 21. To
a solution of 1-(benzotriazol-1-yl)-1-phenoxyalkane 10a ,b (5
mmol) in THF (70 mL) was added n-butyllithium (2.2 M in
cyclohexane, 2.3 mL, 5.0 mmol) at -78 °C. The solution was
stirred at this temperature for 5 min, and the appropriate
electrophile (Ph(CH2)3Br, 4-tolualdehyde, or 2-cyclohexenone,
5 mmol) was added. The solution was kept at this temperature
for 5 min (for 12d , the reaction mixture was warmed to 20 °C
and kept at this temperature for an additional 2 min). Then
the solution was quenched with water (10 mL), extracted with
diethyl ether (3 × 100 mL) and dried over anhydrous MgSO4.
Evaporation of the solvent gave residues, that were purified
by column chromatography on silica gel to give the corre-
sponding intermediates 12d , 14b, and 20, which were sepa-
rately dissolved in a mixture of ethanol (20 mL), water (20
mL), and H2SO4 (2 mL) and refluxed for 10-15 min. Water
(80 mL) was then added, the solution was extracted with
diethyl ether (3 × 100 mL), and the combined extracts were
washed with NaOH solution (2 N, 2 × 100 mL) and dried over
anhydrous MgSO4. Evaporation of the solvent gave residues
that were chromatographed on silica gel (hexane/EtOAc 30:1)
to give the ketones 13d , 15b, and 21. Elemental analyses and
high resolution mass spectra measurements for 13d , 15b, and
21 are shown in Table 1.
3-(Ben zotr ia zol-1-yl)-3-p h en oxy-1-p h en yln on a n e (12d )
was obtained as a colorless oil: yield 83%; 1H NMR δ 0.78 (t,
3 H, J ) 6.6 Hz), 1.00-1.55 (m, 6 H), 1.69-1.87 (m, 2 H), 2.42-
2.75 (m, 6 H), 6.37 (d, 2 H, J ) 8.1 Hz), 6.91 (t, 1 H, J ) 7.5
Hz), 7.01-7.06 (m, 4 H), 7.10-7.24 (m, 3 H), 7.26-7.37 (m, 2
H), 7.87 (d, 1 H, J ) 7.7 Hz), 8.10 (d, 1 H, J ) 7.4 Hz); 13C
NMR δ 13.8, 22.2, 22.4, 24.5, 31.4, 34.3, 35.0, 35.2, 98.0, 112.9,
119.6, 119.9, 123.3, 124.1, 125.9, 127.5, 128.2, 128.3, 129.3,
132.3, 141.2, 146.8, 153.7; HRMS calcd for C27H31N3O 414.2545
(M + 1), found 414.2546.
Exp er im en ta l Section
Gen er a l Com m en ts. Melting points were determined on
a hot stage apparatus without correction. 1H (300 MHz) and
13C NMR (75 MHz) spectra were recorded on a Gemini-300
spectrometer in CDCl3 with TMS or CDCl3, respectively, as
the internal reference. Elemental analyses were performed
using a Carlo Erba 1106 elemental analyzer. High-resolution
mass spectra were measured on an AEI-30 mass spectrometer.
Column chromatography was carried out on MCB silica gel
(230-400 mesh). Tetrahydrofuran (THF) was freshly distilled
from sodium-benzophenone. Lithiation reactions were carried
out under the protection of dry nitrogen.
Compounds 9a ,b were prepared according to the literature
procedure.10
1-(Ben zotr ia zol-1-yl)-1-ch lor oh exa n e (9a ) was obtained
1
as a light brown oil: yield 70%; H NMR δ 0.88 (t, 3 H, J )
7.1 Hz), 1.24-1.44 (m, 4 H), 1.48-1.63 (m, 2 H), 2.67-2.81
(m, 2 H), 6.77 (t, 1 H, J ) 7.4 Hz), 7.44 (t, 1 H, J ) 7.7 Hz),
7.57 (t, 1 H, J ) 7.6 Hz), 7.78 (d, 1 H, J ) 8.4 Hz), 8.12 (d, 1
H, J ) 8.4 Hz); 13C NMR δ 13.6, 22.0, 25.6, 30.5, 37.5, 70.9,
110.4, 120.2, 124.5, 128.0, 131.3, 146.5. Anal. Calcd for
C12H16N3Cl: C, 60.63; H, 6.78; N, 17.68. Found: C, 60.90; H,
7.01; N, 17.48.
1-(Ben zotr ia zol-1-yl)-1-ch lor od od eca n e (9b) was ob-
tained as a light brown oil: yield 82%; 1H NMR δ 0.88 (t, 3 H,
J ) 6.6 Hz), 1.20-1.64 (m, 18 H), 2.60-2.83 (m, 2 H), 6.72 (t,
1 H, J ) 7.5 Hz), 7.44 (t, 1 H, J ) 7.7 Hz), 7.57 (t, 1 H, J ) 7.7
Hz), 7.75 (d, 1 H, J ) 8.4 Hz), 8.12 (d, 1 H, J ) 8.4 Hz); 13C
NMR δ 14.0, 22.6, 26.0, 28.5, 29.1, 29.2, 29.3, 29.4, 31.8, 37.7,
(29) Wedler, C.; Kunath, A.; Schick, H. Angew. Chem., Int. Ed. Engl.
1995, 34, 2028.
(30) In Dictionary of Organic Compounds, 5th ed.; Buckingham, J .,
Donaghy, S. M., Eds.; Chapman and Hall: New York, 1982; Vol. 2, p
5163.
(31) Hegedus, L. S.; Kendall, P. M.; Lo, S. M.; Sheats, J . R. J . Am.
Chem. Soc. 1975, 97, 5448.
(32) Studt, P. Liebigs Ann. Chem. 1965, 693, 90.
(33) Waas, J . R.; Sidduri, A.; Knochel, P. Tetrahedron Lett. 1992,
33, 3717.
(34) Savoia, D.; Trombini, C.; Umani-Ronchi, A. J . Org. Chem. 1978,
43, 2907.
(35) Kulkarni, S. U.; Lee, H. D.; Brown, H. C. J . Org. Chem. 1980,
45, 4542.
2-(Ben zotr ia zol-1-yl)-2-p h en oxy-1-h yd r oxy-1-(4-m eth -
ylp h en yl)h ep ta n e (14b) was obtained as a colorless solid:
yield 80%; mp 146-149 °C (a mixture of two diasteromers,
1
ratio: ca. 4:1); H NMR δ 0.70-0.80 (m, 3 H), 1.05-1.25 (m,
4 H), 1.42-1.55 (m, 2 H), 2.21 (s) and 2.26(s) (total 3 H), 2.62-
2.72 (m, 2 H), 3.36 (d, J ) 4.5 Hz) and 3.54 (d, J ) 2.7 Hz)
(total 1 H), 5.44 (d, J ) 4.6) and 5.57 (d, J ) 2.9 Hz) (total 1
H), 6.50-7.32 (m, 11 H), 7.85-7.92 (m, 1 H), 8.00-8.05 (m, 1

7556 J . Org. Chem., Vol. 61, No. 21, 1996
Katritzky et al.
H); 13C NMR δ 13.7, 15.2, 21.0, 21.1, 21.9, 22.0, 22.2, 22.7,
31.7, 32.8, 77.3, 78.1, 99.0, 113.3, 114.5, 119.1, 119.2, 119.3,
119.4, 123.3, 123.4, 123.7, 123.9, 127.0, 127.1, 127.4, 128.4,
128.6, 129.3, 129.4, 134.1, 134.2, 138.0, 138.3, 146.0, 153.9.
Anal. Calcd for C26H29N3O2: C, 75.15; H, 7.03; N, 10.11.
Found: C, 75.07; H, 7.36; N, 9.99.
3-[1-P h e n oxy-1-(b e n zot r ia zol-1-yl)h e xyl]cycloh e x-
a n on e (20) was obtained as a colorless oil: yield 48% (a
mixture of two diasteromers, ratio ca. 3:1); 1H NMR δ 0.72 (t,
3 H, J ) 6.9 Hz), 0.81-1.70 (m, 9 H), 1.86-2.48 (m, 5 H), 2.52-
3.24 (m, 3 H), 6.56 (d, J ) 8.1 Hz) and 6.66 (d, J ) 8.3 Hz)
(total 2 H), 6.93 (t, 1 H, J ) 7.4 Hz), 7.07 (t, 2 H, J ) 7.8 Hz),
7.78(d, J ) 8.7 Hz) and 7.87 (d, J ) 8.7 Hz) (total 1 H), 8.08
(d, 1 H, J ) 6.9 Hz); 13C NMR δ 13.2, 21.3, 21.7, 23.9, 25.1,
30.9, 31.9, 40.2, 42.4, 47.2, 99.1, 113.6, 119.1, 119.3, 123.0,
123.5, 127.3, 128.8, 133.4, 145.4, 153.1, 208.6. Anal. Calcd
for C24H29N3O2: C, 73.61; H, 7.47; N, 10.74. Found: C, 73.80;
H, 7.66; N, 10.38.
1-Hyd r oxy-1,1-d ip h en ylh ep ta n -2-on e (17) was obtained
as a colorless oil: yield 76%; H NMR δ 0.79 (t, 3 H, J ) 7.1
1
Hz), 1.08-1.25 (m, 4 H), 1.40-1.50 (m, 2 H), 2.55 (t, 2 H, J )
7.7 Hz), 4.93 (s, 1 H), 7.25-7.33 (m, 10 H); 13C NMR δ 13.6,
22.1, 23.9, 31.0, 38.2, 85.4, 127.9, 128.2, 141.5, 211.1.
1-(P h en yla m in o)-1-p h en yltr id eca n -2-on e (19) was ob-
tained as a colorless solid: yield 74%; mp 50-51 °C; 1H NMR
δ 0.88 (t, 3 H, J ) 6.8 Hz), 1.10-1.55 (m, 18 H), 2.41 (t, 2 H,
J ) 7.4 Hz), 4.99 (d, 1 H, J ) 4.5 Hz), 5.48 (d, 1 H, J ) 4.5
Hz), 6.56 (d, 2 H, J ) 8.7 Hz), 6.64 (t, 1 H, J ) 7.4 Hz), 7.08(t,
2 H, J ) 7.4 Hz), 7.30-7.40 (m, 3 H); 7.44 (d, 2 H, J ) 8.1
Hz); 13C NMR δ 14.1, 22.7, 23.9, 28.9, 29.2, 29.3, 29.4, 29.5,
29.6, 31.9, 39.1, 67.7, 113.3, 117.6, 127.9, 128.3, 129.1, 138.2,
146.1, 206.4.
P r ep a r a tion of Keton es 24 a n d 25. To a solution of
1-(benzotriazol-1-yl)-1-phenoxyhexane (10a ) (5 mmol) in THF
(70 mL) was added n-butyllithium (2.2 M in cyclohexane, 2.3
mL, 5.0 mmol) at -78 °C. The solution was stirred at this
temperature for 5 min, and then trans-chalcone (1.05 g, 5
mmol) was added. The solution was kept at this temperature
for 5 min and then quenched with water (10 mL), extracted
with diethyl ether (3 × 100 mL), and dried over anhydrous
MgSO4. Evaporation of the solvent gave residues, which un-
derwent a short column on silica gel to give the corresponding
intermediates 22 and 23. The intermediates 22 and 23 were
separately dissolved in a mixture of ethanol (20 mL), water
(20 mL), and H2SO4 (2 mL) and refluxed for 10-15 min. Water
(80 mL) was then added, the solution was extracted with
diethyl ether (3 × 100 mL), and the combined extracts were
washed with NaOH solution (2 N, 2 × 100 mL) and dried over
anhydrous MgSO4. Evaporation of the solvent gave residues,
that were chromatographed on silica gel (hexane/AcOEt 50:1)
to give the ketones 24 and 25. Elemental analyses and high-
resolution mass measurements are given in Table 1.
1-P h en yln on a n -4-on e (13d ) was obtained as a colorless
oil: yield 96%; 1H NMR δ 0.88 (t, 3 H, J ) 6.9 Hz), 1.18-1.37
(m, 4 H), 1.50-1.60 (m, 2 H), 1.84-1.95 (m, 2 H), 2.30-2.40
(m, 4 H), 2.60 (t, 2 H, J ) 7.5 Hz), 7.14-7.19 (m, 3 H), 7.23-
7.29 (m, 2 H); 13C NMR δ 13.8, 22.3, 23.4, 25.1, 31.3, 35.0,
41.7, 42.7, 125.8, 128.2, 128.3, 141.5, 210.8.
1-Hyd r oxy-1-(4-m eth ylp h en yl)h ep ta n -2-on e (15b) was
1
obtained as a colorless oil: yield 95%; H NMR δ 0.82 (t, 3 H,
J ) 7.2 Hz), 1.10-1.28 (m, 4 H), 1.45-1.55 (m, 2 H), 2.30-
2.38 (m, 5 H), 4.30 (br s, 1 H), 5.05 (s, 1 H), 7.19 (s, 5 H); 13C
NMR δ 13.7, 21.1, 22.2, 23.3, 31.0, 37.7, 79.4, 127.2, 129.5,
135.2, 138.3, 209.8.
3-Hexa n oylcycloh exa n on e (21) was obtained as a color-
less oil: yield 90%; 1H NMR δ 0.89 (t, 3 H, J ) 6.6 Hz), 1.20-
1.38 (m, 4 H), 1.52-1.88 (m, 5 H), 2.01-2.18 (m, 2 H), 2.28-
2.59 (m, 6 H), 2.86-2.97 (m, 1 H); 13C NMR δ 13.6, 22.2, 23.0,
24.7, 27.1, 31.1, 40.7, 40.8, 42.3, 49.9, 209.8, 210.5.
1,3-Dip h en yln on a n e-1,4-d ion e (24) was obtained as a
1
Gen er a l P r oced u r e for th e P r ep a r a tion of Keton es
13a -c, 15a , 17, a n d 19. To a solution of 1-(benzotriazol-1-
yl)-1-phenoxyalkane 10a or 10b (5 mmol) in THF (70 mL) was
added n-butyllithium (2.2 M in cyclohexane, 2.3 mL, 5.0 mmol)
at -78 °C, and the solution was stirred at this temperature
for 2 min. The appropriate electrophile (EtBr, BuBr, PhCHO,
PhCOPh, or PhCHdNPh, 5 mmol) was added, and the solution
was kept at this temperature for 5 min (for 13a -c, the reaction
mixture was warmed to 20 °C and kept at this temperature
for additional 2 min). The reaction was then quenched with
water (10 mL) and evaporated in vacuo to give a residue, which
was dissolved in a mixture of ethanol (20 mL), water (20 mL),
and H2SO4 (2 mL) and refluxed for 10-15 min. Water (80 mL)
was added, the solution was extracted with diethyl ether (3 ×
100 mL), and the combined extracts were washed with NaOH
solution (2 N, 2 × 100 mL) and dried over anhydrous MgSO4.
Evaporation of the solvents and purification by column chro-
matography (hexane/AcOEt 30:1) gave the ketones 13a -c,
15a , 17, and 19. Elemental analyses and high resolution mass
measurements for 13a -c, 15a , 17, and 19 are given in Table 1.
3-Tetr a d eca n on e (13a ) was obtained as a colorless oil:
yield 88%; 1H NMR δ 0.89 (t, 3 H, J ) 6.6 Hz), 1.05 (t, 3 H, J
) 7.4 Hz), 1.20-1.26 (m, 16 H), 1.51-1.60 (m, 2 H), 2.35-
2.45 (m, 4 H); 13C NMR δ 7.8, 14.0, 22.6, 23.9, 29.3, 29.4, 29.5,
29.6, 31.9, 35.8, 42.4, 211.7.
colorless oil: yield 33%; H NMR δ 0.81 (t, 3 H, J ) 7.1 Hz),
1.10-1.30 (m, 4 H), 1.45-1.65 (m, 2 H), 2.40-2.70 (m, 2 H),
3.12 (dd, 1 H, J ) 18.1, 3.6 Hz), 4.04 (dd, 1 H, J ) 18.0, 10.2
Hz), 4.43 (dd, 1 H, J ) 10.2, 3.6 Hz), 7.26-7.57 (m, 8 H), 7.94-
7.98 (m, 2 H); 13C NMR δ 13.8, 22.3, 23.3, 31.1, 41.7, 42.3,
53.3, 127.4, 128.0, 128.3, 128.5, 129.0, 133.1, 136.5, 138.2,
198.1, 209.3.
1,3-Dip h en yl-3-h yd r oxy-1-n on en -4-on e (25) was ob-
1
tained as a colorless oil: yield 23%; H NMR δ 0.82 (t, 3 H, J
) 6.9 Hz), 1.10-1.30 (m, 4 H), 1.45-1.65 (m, 2 H), 2.40-2.60
(m, 2 H), 4.89 (s, 1 H), 6.87 (d, 1 H, J ) 15.8 Hz), 7.04 (d, 1 H,
J ) 15.8 Hz), 7.20-7.50 (m, 10 H); 13C NMR δ 13.7, 22.2, 23.8,
31.0, 37.0, 83.1, 126.7, 126.8, 127.0, 128.0, 128.2, 128.6, 128.7,
132.5, 136.3, 141.2, 209.2.
Gen er a l P r oced u r e for th e Lith ia tion of Com p ou n d
26. P r ep a r a tion of th e In ter m ed ia tes 29a ,b a n d 33a ,
Keton es 30a ,b, a n d Alk yn oylsila n e 34a . To a solution of
1-(phenoxymethyl)benzotriazole (26) (1.13 g, 5 mmol) in THF
(70 mL) at -78 °C was added n-butyllithium (2.2 M in
cyclohexane, 2.3 mL, 5 mmol) and the solution stirred for 2
min at this temperature. The appropriate electrophile (PhCH2-
Br or MeI, 5 mmol) was added, and the mixture was stirred
at this temperature for 5 min and then at room temperature
for an additional 5 min. The solution was cooled to -78 °C
again, and a second equivalent of BuLi (2.2 M in cyclohexane,
2.3 mL, 5 mmol) was added. After addition of a second
electrophile (p-tolualdehyde, cyclohexanal, or Me3SiCl, 5 mmol),
the solution was kept at -78 °C for 5 min and then quenched
with water (20 mL) (for 33a the reaction was quenched at room
temperature), extracted with diethyl ether (3 × 100 mL) and
dried over anhydrous MgSO4. Evaporation of the solvent gave
residues, that were purified by column chromatography on
silica gel (hexane/AcOEt 100:1) to give 29a ,b and 33a . Then
29a (or 29b, 33a ) was dissolved in a mixture of ethanol (20
mL), water (20 mL), and H2SO4 (2 mL) and refluxed for 10-
15 min. Water (80 mL) was added, the solution was extracted
with diethyl ether (3 × 100 mL), and the combined extracts
were washed with NaOH solution (2 N, 100 mL × 2) and dried
over anhydrous MgSO4. Evaporation of the solvent gave a
residue that was chromatographed on silica gel (hexane/AcOEt
200:1) to give 30a ,b or 34a . Elemental analyses and high-
5-Hexa d eca n on e (13b) was obtained as a colorless oil:
1
yield 90%; H NMR δ 0.86-0.94 (m, 6 H), 1.20-1.38 (m, 18
H), 1.51-1.61 (m, 4 H), 2.37-2.42 (m, 4 H); 13C NMR δ 13.8,
14.0, 22.3, 22.6, 23.8, 25.9, 29.2, 29.3, 29.4, 29.5, 29.6, 31.8,
42.4, 42.8, 211.6.
6-Tetr a d eca n on e (13c) was obtained as a colorless oil:
1
yield 81%; H NMR δ 0.86-0.91 (m, 6 H), 1.20-1.48 (m, 14
H), 1.50-1.62 (m, 2 H), 1.80-1.90 (m, 2 H), 2.38 (t, 2 H, J )
7.5 Hz), 3.39 (t, 2 H, J ) 6.8 Hz); 13C NMR δ 13.7, 13.9, 22.4,
22.5, 23.4, 23.8, 29.1, 29.2, 29.3, 31.4, 31.5, 31.7, 42.6, 210.9.
1-Hyd r oxy-1-p h en ylh ep ta n -2-on e (15a ) was obtained as
a colorless oil: yield 63%; 1H NMR δ 0.82 (t, 3 H, J ) 7.1 Hz),
1.10-1.25 (m, 4 H), 1.40-1.60 (m, 2 H), 2.25-2.40 (m, 2 H),
4.42 (br s, 1 H), 5.08 (s, 1 H), 7.30-7.40 (m, 5 H); 13C NMR δ
13.7, 22.1, 23.3, 31.0, 37.7, 79.6, 127.3, 128.5, 128.8, 138.1,
209.6.

Syntheses of Dialkyl Ketones and Alkanoylsilanes
J . Org. Chem., Vol. 61, No. 21, 1996 7557
resolution mass spectra measurements for 30a ,b and 34 are
shown in Table 1.
1.17-1.47 (m, 20 H), 1.50-1.71 (m, 4 H), 2.41 (t, 4 H, J ) 7.4
Hz); 13C NMR δ 14.0, 22.6, 23.9, 29.1, 29.2, 29.3, 31.8, 42.8,
211.4.
9-Non a d eca n on e (28b) was obtained as a colorless solid:
yield 80%; mp 45-47 °C; 1H NMR δ 0.87 (t, 6 H, J ) 6.8 Hz),
1.15-1.40 (m, 24 H), 1.50-1.67 (m, 4 H), 2.37 (t, 4 H, J ) 7.5
Hz); 13C NMR δ 14.0, 22.6, 23.8, 29.1, 29.2, 29.3, 29.4, 29.5,
29.6, 31.7, 31.8, 42.7, 211.4.
2-(Ben zotr ia zol-1-yl)-1-h yd r oxy-1-(4-m eth ylp h en yl)-3-
p h en yl-2-p h en oxyp r op a n e (29a ) was obtained as a colorless
solid: yield 64%; mp 165-167 °C; 1H NMR δ 2.28 (s, 3 H),
3.86 (d, 1 H, J ) 15.1 Hz), 4.17 (d, 1 H, J ) 15.1 Hz), 4.83 (d,
1 H, J ) 3.0 Hz), 6.01 (s, 1 H), 6.48 (dd, 2 H, J ) 7.7, 1.1 Hz),
6.84-7.15 (m, 15 H), 7.93 (dd, 1 H, J ) 8.4, 0.9 Hz); 13C NMR
δ 21.0, 39.5, 76.4, 98.7, 114.0, 117.8, 119.0, 122.6, 123.8, 126.9,
127.2, 127.9, 128.0, 128.4, 129.5, 131.1, 133.9, 134.2, 134.3,
138.1, 145.2, 154.2. Anal. Calcd for C28H25N3O2: C, 77.22;
H, 5.79; N, 9.65. Found: C, 77.11; H, 5.70; N, 9.61.
1-(1-Hyd r oxycycloh exyl)h exa n -1-on e (32) was obtained
1
as a colorless oil: yield 41%; H NMR δ 0.89 (t, 3 H, J ) 6.9
Hz), 1.20-1.38 (m, 5 H), 1.40-1.50 (m, 2 H), 1.53-1.78 (m, 9
H), 2.57 (t, 2 H, J ) 7.4 Hz), 3.63 (br s, 1 H); 13C NMR δ 13.7,
21.0, 22.3, 23.3, 25.2, 31.3, 33.7, 35.5, 77.8, 214.8.
2-(Ben zotr ia zol-1-yl)-2-p h en oxy-1-h yd r oxy-1-cycloh ex-
ylp r op a n e (29b) was obtained as a colorless solid: yield 45%;
mp 150-151 °C; 1H NMR δ 1.12-1.54 (m, 5 H), 1.62-2.00 (m,
6 H), 2.16 (s, 3 H), 2.90 (d, 1 H, J ) 5.7 Hz), 4.15-4.20 (m, 1
H), 6.45 (d, 2 H, J ) 7.5 Hz), 6.98 (t, 1 H, J ) 8.1 Hz), 7.10 (t,
2 H, J ) 8.0 Hz), 7.30 (t, 1 H, J ) 7.7 Hz), 7.39 (t, 1 H, J ) 8.3
Hz), 7.95 (t, 2 H, J ) 8.4 Hz); 13C NMR δ 18.6, 26.0, 26.2, 26.5,
28.1, 32.0, 39.5, 79.5, 98.4, 113.2, 119.6, 120.4, 123.9, 124.1,
127.4, 129.4, 132.4, 146.4, 153.3. Anal. Calcd for
C21H25N3O2: C, 71.77; H, 7.17; N, 11.96. Found: C, 72.08; H,
7.35; N, 12.08.
Gen er a l P r oced u r e for th e Lith ia tion of Com p ou n d
26. P r ep a r a tion of 34b-g a n d 37. To a solution of
1-(phenoxymethyl)benzotriazole (26) (1.13 g, 5 mmol) in THF
(70 mL) at -78 °C was added n-butyllithium (2.2 M in
cyclohexane, 2.3 mL, 5 mmol) and the solution stirred for 2
min at this temperature. The appropriate trialkylsilyl chloride
[Me3SiCl, PhMe2SiCl, Ph3SiCl, (n-C8H17)Me2SiCl, (t-Bu)Me2-
SiCl, (i-Pr)3SiCl] was added, and the mixture was stirred at
this temperature for 5 min, adding a second equiv of BuLi (2.2
M in cyclohexane, 2.3 mL, 5 mmol). The solution was kept at
-78 °C for an additional 2 min before a second electrophile
(n-C8H17Br, PhCH2Br, n-C7H15Br, EtBr, or cyclohexenone).
Then the solution was stirred at -78 °C for 5 min and then at
room temperature for an additional 5 min. Water (20 mL) and
HCl (5 N, 15 mL) were added, and the mixture was refluxed
for 7 h. After cooling, the solution was extracted with diethyl
ether (3 × 100 mL), and the combined extracts were washed
with NaOH solution (2 N, 2 × 100 mL) and dried over
anhydrous MgSO4. Evaporation of the solvent gave residues,
that were purified by column chromatography on silica gel
(hexane/EtOAc 50:1). Elemental analysis data are shown in
Table 1.
[1-(Be n zot r ia zol-1-yl)-1-p h e n oxy-2-p h e n yle t h yl]t r i-
m eth ylsila n e (33a ) was obtained as a colorless solid: yield
90%; mp 115-117 °C; 1H NMR δ 0.20 (s, 9 H), 3.52 (d, 1 H, J
) 14.1 Hz), 3.72 (d, 1 H, J ) 14.1), 6.45 (d, 2 H, J ) 7.5 Hz),
6.88-7.40 (m, 11 H), 7.98 (d, 1 H, J ) 8.4 Hz); 13C NMR δ 0.2,
45.7, 95.8, 113.6, 119.1, 123.3, 123.8, 126.8, 127.0, 129.0, 129.1,
131.2, 133.8, 135.0, 145.6, 156.3. Anal. Calcd for C23H25N3-
OSi: C, 71.28; H, 6.50; N, 10.84. Found: C, 71.04; H, 6.58;
N, 10.86.
1-H y d r o x y -1-(4-m e t h y lp h e n y l)-3-p h e n y lp r o p a n -2-
on e (30a ) was obtained as a colorless solid: yield 82%; mp
92-93 °C; 1H NMR δ 2.39 (s, 3 H), 3.65 (s, 2 H), 4.23 (d, 1 H,
J ) 4.5 Hz), 5.17 (d, 1 H, J ) 4.8 Hz), 7.02-7.07 (m, 2 H),
7.21 (s, 3 H), 7.24-7.32 (m, 4 H); 13C NMR δ 21.2, 44.5, 78.9,
127.2, 127.6, 128.6, 129.4, 129.7, 133.0, 134.6, 138.7, 207.1.
Non a n oyltr im eth ylsila n e (34b) was obtained as a yellow
1
oil: yield 82%; H NMR δ 0.21 (s, 9 H), 0.89 (t, 3 H, J ) 6.9
Hz), 1.20-1.35 (m, 10 H), 1.48-1.54 (m, 2 H), 2.60 (t, 2 H, J
) 7.4 Hz); 13C NMR δ -3.2, 14.0, 22.1, 22.6, 29.1, 29.3, 29.4,
31.8, 48.4, 248.3.
1-Cycloh exyl-1-h yd r oxy-2-p r op a n on e (30b ) was ob-
tained as a colorless oil: yield 95%; 1H NMR δ 1.15-1.90 (m,
11 H), 2.22 (s, 3 H), 3.51 (br s, 1 H), 4.07 (d, 1 H, J ) 2.4 Hz);
13C NMR δ 25.0, 25.5, 25.8, 25.9, 26.4, 29.9, 41.0, 81.1, 209.9.
Dim eth ylp h en ylocta n oylsila n e (34c) was obtained as a
1
yellow oil: yield 96%; H NMR δ 0.48 (s, 6 H), 0.84 (t, 3 H, J
) 6.9 Hz), 1.10-1.30 (m, 8 H), 1.41-1.46 (m, 2 H), 2.55 (t, 2
H, J ) 7.2 Hz), 7.35-7.39 (m, 3 H), 7.53-7.56 (m, 2 H); 13C
NMR δ -4.7, 14.0, 22.2, 22.5, 29.0, 29.2, 31.6, 48.8, 128.1,
129.8, 133.9, 134.6, 246.3.
(P h en yla cetyl)tr im eth ylsila n e (34a ) was obtained as a
1
yellow oil: yield 91%; H NMR δ 0.12 (s, 9 H), 3.85 (s, 2 H),
7.13 (d, 2 H, J ) 8.4 Hz), 7.23-7.31 (m, 3 H); 13C NMR δ -2.9,
Tr ip h en ylp r op ion ylsila n e (34d ) was obtained as a yellow
55.4, 126.8, 128.5, 129.9, 133.1, 243.8.
1
oil: yield 85%; H NMR δ 0.96 (t, 3 H, J ) 7.1 Hz), 2.75 (q, 2
H, J ) 7.1 Hz), 7.36-7.48 (m, 9 H), 7.58-7.61 (m, 6 H); 13C
NMR δ 6.2, 44.0, 128.2, 130.2, 131.4, 136.1, 243.1.
Gen er a l P r oced u r e for th e Lith ia tion of Com p ou n d
26. P r ep a r a tion of 28a ,b a n d 32. To a solution of 1-(phe-
noxymethyl)benzotriazole (26) (1.13 g, 5 mmol) in THF (70 mL)
at -78 °C was added n-butyllithium (2.2 M in cyclohexane,
2.3 mL, 5 mmol) and the solution stirred for 2 min at this
temperature. The appropriate electrophile (n-C8H17Br, PhCH2-
Br, or n-C5H11I) was added, and the mixture was stirred at
this temperature for 5 min and then at room temperature for
an additional 5 min. The solution was cooled to -78 °C again,
and a second equivalent of BuLi (2.2 M in cyclohexane, 2.3
mL, 5 mmol) was added. After addition of a second electro-
phile (n-C8H17Br, n-C10H21Br, or cyclohexanone), the solution
was kept at -78 °C for 5 min and then at room temperature
for an additional 5 min. Then the solution was quenched with
water (20 mL) (in the case 32; it was quenched at -78 °C)
and evaporated under reduced pressure to give a residue,
which was directly hydrolyzed by refluxing in a mixture of
ethanol (20 mL), water (20 mL), and H2SO4 (2 mL) for 10-15
min. Water (80 mL) was then added, the solution was
extracted with diethyl ether (3 × 100 mL), and the combined
extracts were washed with NaOH solution (2 N, 2 × 100 mL)
and dried over anhydrous MgSO4. Evaporation of the solvent
gave residues that were purified by column chromatography
on silica gel (hexane/EtOAc 50:1). Elemental analyses and
high-resolution mass spectra measurements are shown in
Table 1.
Dim eth yloctylp r op ion ylsila n e (34e) was obtained as a
1
yellow oil: yield 71%; H NMR δ 0.19 (s, 6 H), 0.68-0.73 (m,
2 H), 0.86-0.91 (m, 3 H), 0.98 (t, 3 H, J ) 7.2 Hz), 1.20-1.37
(m, 12 H), 2.62 (q, 2 H, J ) 7.2 Hz); 13C NMR δ-4.9, 6.0, 13.5,
14.0, 22.6, 23.5, 29.1, 31.8, 33.3, 41.9, 248.2.
ter t-Bu tyld im eth yln on a n oylsila n e (34f) was obtained as
a yellow oil: yield 56%; 1H NMR δ 0.17 (s, 6 H), 0.87 (t, 3 H, J
) 6.6 Hz), 0.92 (s, 9 H), 1.17-1.33 (m, 10 H), 1.42-1.53 (m,
2H), 2.58 (t, 2 H, J ) 7.2 Hz); 13C NMR δ -7.0, 14.0, 16.5,
21.9, 22.6, 26.4, 29.1, 29.3, 29.5, 31.8, 50.3, 247.9.
P r op ion yltr iisop r op ylsila n e (34g) was obtained as a
yellow oil: yield 46%; 1H NMR δ 0.99 (t, 3 H, J ) 7.1 Hz); 1.12-
(d, 18 H, J ) 6.9 Hz); 1.29 (hept, 3 H, J ) 6.9 Hz), 2.61 (q, 2
H, J ) 7.1 Hz); 13C NMR δ 5.7, 10.7, 18.5, 44.3, 247.4.
3-[(Tr im eth ylsilyl)ca r bon yl]cycloh exa n on e (37) was
1
obtained as a yellow oil: yield 66%; H NMR δ 0.25 (s, 9 H),
1.50-2.50 (m, 8 H), 3.28-3.38 (m, 1 H); 13C NMR δ -3.0, 24.8,
25.5, 40.9, 53.9, 210.4, 245.8.
Su p p or tin g In for m a tion Ava ila ble: The NMR spectra
of compounds 9b, 12d , 17, 19, 24, and 25 (12 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
9-Hep ta d eca n on e (28a ) was obtained as a colorless solid:
yield 97%; mp 48-50 °C; 1H NMR δ 0.91 (t, 6 H, J ) 6.8 Hz),
J O960830O