Novel and efficient insertions of carbons carrying O-, S-, and N-Linked substituents: Synthesis of α-alkoxyalkyl, α-(Alkylthio)alkyl, and α-(Carbazol-9-yl)alkyl ketones

Article abstract of DOI:10.1021/jo960840p

A wide variety of benzotriazolyl-stabilized anions 2, obtained by the lithiation of 1-(α-alkoxyalkyl)-, 1-[α-(alkylthio)alkyl]-, and 1-[α-(carbazol-9-yl)alkyl]benzotriazoles 1, on reaction with aliphatic and aromatic aldehydes and ketones, followed by rearrangement induced by heating in the presence of zinc bromide, furnish one-carbon-homologated α-alkoxyalkyl, α-(alkylthio)alkyl, and α-(carbazol-9-yl)alkyl ketones 4 in simple one-pot operations in good yields with excellent regioselectivity. In several alkoxymethylene insertions, intermediate 2-alkoxyoxiranes were separated in good yields, demonstrating the epoxide mechanism for the rearrangements and providing a facile approach to poly substituted 2-alkoxyoxiranes, another class of important compounds.

Full text of DOI:10.1021/jo960840p

7564
J . Org. Chem. 1996, 61, 7564-7570
Novel a n d Efficien t In ser tion s of Ca r bon s Ca r r yin g O-, S-, a n d
N-Lin k ed Su bstitu en ts: Syn th esis of r-Alk oxya lk yl,
r-(Alk ylth io)a lk yl, a n d r-(Ca r ba zol-9-yl)a lk yl Keton es
Alan R. Katritzky,* Linghong Xie, and Larisa Serdyuk
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received May 7, 1996X
A wide variety of benzotriazolyl-stabilized anions 2, obtained by the lithiation of 1-(R-alkoxyalkyl)-,
1-[R-(alkylthio)alkyl]-, and 1-[R-(carbazol-9-yl)alkyl]benzotriazoles 1, on reaction with aliphatic and
aromatic aldehydes and ketones, followed by rearrangement induced by heating in the presence of
zinc bromide, furnish one-carbon-homologated R-alkoxyalkyl, R-(alkylthio)alkyl, and R-(carbazol-
9-yl)alkyl ketones 4 in simple one-pot operations in good yields with excellent regioselectivity. In
several alkoxymethylene insertions, intermediate 2-alkoxyoxiranes were separated in good yields,
demonstrating the epoxide mechanism for the rearrangements and providing a facile approach to
polysubstituted 2-alkoxyoxiranes, another class of important compounds.
In tr od u ction
methoxymethyl phenyl sulfone anions to cyclic ketones,
followed by a one-carbon ring expansion initiated by
aluminum-based Lewis acids. The initial examples were
limited to cyclobutanones and cyclopentanones in poly-
cyclic systems,2 but by using zirconium tetrachloride as
the Lewis acid, the method was recently extended to
monocyclic and acyclic ketones;3 however, such insertions
into aldehydes remain unreported. Recently, we de-
scribed a facile conversion of aldehydes to R-acetoxy-
methyl ketones via reactions of aldehydes with (benzo-
triazolyl)phenoxy methyl anion, followed by the treat-
ment of the resulting adducts with p-toluenesulfonic acid
in acetic acid.5 However, acetoxymethylene insertions of
this type are restricted to aldehydes.
The lithium derivatives of bis(phenylthio)methane4 and
of (phenylthio)methyl phenyl sulfone2 add to carbonyl
compounds, and subsequent rearrangement of the ad-
ducts formed enables successful (phenylthio)methylene
homologation of aldehydes and ketones. However, excess
diethylaluminum chloride was needed to promote the
addition reaction of (phenylthio)methyl phenyl sulfone
anion to ketones. The yields were moderate, and all of
these methods apparently require the isolation of the
addition adducts. The successful bis(methylthio)meth-
ylene insertion developed by Knapp et al. to transform
cyclic ketones to 1,2-keto thioketals via the reaction of
(MeS)3CLi with ketones, followed by the ring expansion
assisted by CuBF3‚4MeCN15 as reported is limited to
cyclic ketones. At the higher oxidation level, Yamakawa
et al. have described an easy transformation of alde-
hydes7d and ketones7c to one-carbon-homologated R-sulfi-
nylalkyl ketones via carbenoid intermediates using chlo-
romethyl phenyl sulfoxide as the reagent.
Methods for the homologation of aldehydes and ketones
by carbon-insertions R to the carbonyl group are of
significant importance in organic synthesis as evidenced
by the widespread and continuing interest in the devel-
opment of new approaches.1-12 As R-alkoxyalkyl and
R-(alkylthio)alkyl ketones are important and versatile
intermediates in organic synthesis,13,14 approaches ca-
pable of inserting a heteroatom-substituted carbon such
as -CR(OR′)- or -CR(SR′)- are especially desired.
Most classical carbon insertion methods involve the use
of diazo compounds RCHN2,1,8 which are unsuitable for
large-scale work and often suffer from low regioselectiv-
ity, multiple homologation, and handling difficulties.
Moreover, while diazo sulfones, diazophosphine oxides,
and diazo phosphonates were described to add to alde-
hydes to yield â-keto sulfones, â-keto phosphine oxides,
and â-keto phosphonates,10 no successful alkoxymethyl-
ene and (alkylthio)methylene carbon insertions have been
reported using diazo compounds.
Trost et al. introduced the first alkoxymethylene ho-
mologation methodology, which involves the addition of
X Abstract published in Advance ACS Abstracts, October 1, 1996.
(1) Krow, G. R. Tetrahedron 1987, 43, 3.
(2) Trost, B. M.; Mikhail, G. K. J . Am. Chem. Soc. 1987, 109, 4124.
(3) Montana, J . G.; Phillipson, N.; Taylor, R. J . K. J . Chem. Soc.,
Chem. Commun. 1994, 2289.
(4) (a) Abraham, W. D.; Bhupathy, M.; Cohen, T. Tetrahedron Lett.
1987, 28, 2203. (b) Cohen, T.; Kuhn, D.; Falck, J . R. J . Am. Chem.
Soc. 1975, 97, 4749.
(5) Katritzky, A. R.; Yang, Z.; Moutou, J .-L. Tetrahedron Lett. 1995,
36, 841.
(6) Loeschorn, C. A.; Nakajima, M.; McCloskey, P. J .; Anselme, J .-
P. J . Org. Chem. 1983, 48, 4407.
(7) (a) Satoh, T.; Mizu, Y.; Kawashima, T.; Yamakawa, K. Tetrahe-
dron 1995, 51, 703. (b) Satoh, T.; Itoh, N.; Gengyo, K.; Yamakawa, K.
Tetrahedron Lett. 1992, 33, 7543. (c) Satoh, T.; Hayashi, Y.; Mizu, Y.;
Yamakawa, K. Tetrahedron Lett. 1992, 33, 7181. (d) Satoh, T.; Fujii,
T.; Yamakawa, K. Bull. Chem. Soc. J pn. 1990, 63, 1266.
(8) (a) Maruoka, K.; Concepcion, A. B.; Yamamoto, H. J . Org. Chem.
1994, 59, 4725. (b) Maruoka, K.; Concepcion, A. B.; Yamamoto, H.
Synthesis 1994, 1283.
In the course of our investigation on the use of
benzotriazole derivatives in organic synthesis,16 we found
that the benzotriazolyl moiety is both a good anion-
stabilizing group and a good leaving group. These
properties, coupled with the ready availability of its
derivatives, suggested its potential to provide general and
(9) Kim, S.; Lee, S. Tetrahedron Lett. 1991, 32, 6575.
(10) Holmquist, C. R.; Roskamp, E. J . Tetrahedron Lett. 1992, 33,
1131.
(11) (a) Labar, D.; Laboureur, J . L.; Krief, A. Tetrahedron Lett. 1982,
23, 983. (b) Laboureur, J . L.; Krief, A. Tetrahedron Lett. 1984, 25, 2713.
(12) Uemura, S.; Ohe, K.; Sugita, N. J . Chem. Soc., Chem. Commun.
1988, 111.
(13) Liu, P.; Vandewalle, M. Tetrahedron 1994, 50, 7061.
(14) Trost, B. M. Chem. Rev. 1978, 78, 363.
(15) Knapp, S.; Trope, A. F.; Theodore, M. S.; Hirata, N.; Barchi, J .
J . J . Org. Chem. 1984, 49, 608.
(16) (a) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron
1991, 47, 2683. (b) Katritzky, A. R.; Yang, Z.; Cundy, D. J . Aldrichim.
Acta 1994, 27, 31. (c) Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis
1994, 445. (d) Katritzky, A. R.; Lan, X. Chem. Soc. Rev. 1994, 363.
S0022-3263(96)00840-7 CCC: $12.00 © 1996 American Chemical Society

Synthesis of R-Substituted Alkyl Ketones
J . Org. Chem., Vol. 61, No. 21, 1996 7565
Ta ble 1. Alk oxym eth ylen e In ser tion in to Ald eh yd es a n d Keton es
efficient carbon-insertion methodology. Since disclosure
of our preliminary paper,17 we have further developed
and generalized the regioselective insertion approach to
one-carbon-homologated R-alkoxyalkyl, R-(alkylthio)alkyl,
and R-(carbazol-9-yl)alkyl ketones with many more ex-
amples and now provide full details of this work in this
and the following paper.
benzotriazole (1d ) and 1-[methoxy(4-chlorophenyl)meth-
yl]benzotriazole (1f) were made by a procedure similar
to that used for 1c. 1-(1-Phenoxyhexyl)benzotriazole (1e)
(Table 1) was made by the lithiation of 1-(phenoxymeth-
yl)benzotriazole (1b), followed by the addition of pentyl
iodide.21 Compounds 1d and 1f were previously un-
known and were characterized by their NMR spectra and
CHN analyses.
Resu lts a n d Discu ssion
Treatment of 1a -f with n-butyllithium at -78 °C,
under argon in THF, furnished deep green solutions of
the corresponding anions 2, which reacted smoothly with
aliphatic and aromatic aldehydes and ketones (Scheme
1). Our previous work has shown that these reactions
provided intermediates of type 3, which upon hydrolysis
or methanolysis furnished various R-hydroxy ketones20,21
or methyl acetals22 in sequences in which benzotriazole
Alk oxym eth ylen e In ser tion in to Ald eh yd es a n d
Keton es. 1-(Alkoxymethyl)benzotriazoles 1a ,18 1b,19 and
1c20 (Table 1) were prepared according to our previously
reported procedures. 1-[Ethoxy(4-chlorophenyl)methyl]-
(17) Katritzky, A. R.; Xie, L.; Toader, D.; Serdyuk, L. J . Am. Chem.
Soc. 1995, 117, 12015.
(18) Katritzky, A. R.; Rachwal, S.; Rachwal, B. J . Chem. Soc., Perkin
Trans. 1 1987, 791.
(19) Katritzky, A. R.; Rachwal, S.; Caster, K. C.; Mahni, F.; Law,
K. W.; Rubio, O. J . Chem. Soc., Perkin Trans. 1 1987, 781.
(20) Katritzky, A. R.; Lang, H.; Wang, Z.; Zhang, Z.; Song, H. J .
Org. Chem. 1995, 60, 7619.
(21) Katritzky, A. R.; Lang, H.; Wang, Z.; Lie, Z. J . Org. Chem. 1996,
submitted.
(22) Katritzky, A. R.; Yang, Z.; Cundy, D. J . Synth. Commun. 1993,
23, 3061.

7566 J . Org. Chem., Vol. 61, No. 21, 1996
Katritzky et al.
Sch em e 1a
and various alkoxy groups, while R can be hydrogen,
alkyl, or aryl. As already mentioned, insertions of
carbons carrying both an alkoxy group and an aryl or
alkyl group into carbonyl compounds were previously
unknown. As shown in Table 1, the present methodology
is applicable to diverse aldehydes and ketones: while
alkoxymethylene insertions into aliphatic and aromatic
aldehydes and acyclic ketones gave chain-extended
R-alkoxyalkyl ketones, similar insertions into aromatic
cyclic ketones provided ring-expanded products. How-
ever, as discussed below, analogous insertions into
aliphatic cyclic ketones failed to give ring-expanded
products.
R-Alkoxyalkyl ketones have been previously prepared
by many methods including the R-alkoxylation of ketones
with hypervalent iodine reagents,25 palladium-catalyzed
coupling reaction of acyl chlorides with organotins of the
type MeOCH2SnR3,26 reactions of acyl chlorides or esters
with diazomethane, followed by alcoholysis27 and from
acyl anion equivalents.28 The present approach leading
to one-carbon-homologated R-alkoxyalkyl ketones comple-
ments these methods and should be of substantial
interest in organic synthesis.
Interestingly, when the anion of 1-(methoxymethyl)-
benzotriazole (1a ) reacted with 1-indanone and cinna-
maldehyde after heating in the presence of zinc bromide,
no expected methoxymethylene insertion products of type
4 were obtained. Instead, the corresponding one-carbon
homologated esters, 1-(methoxycarbonyl)indan (8a ) and
methyl 4-phenyl-3-butenoate (8b) were separated in 36%
and 40% yields, respectively. Structures of 8a and 8b
were assigned on the basis of NMR spectra and elemental
analyses. In their 13C NMR spectra, signals typical for
the ester groups appeared at 174.3 and 172.0 ppm. The
formation of these esters 8a and 8b could be accounted
for if epoxides 6 are the intermediates and if 6, instead
of giving oxygen-stabilized cations 5, opened up from the
other side to form cations 9. Subsequent hydride migra-
tion furnished esters 8 (Scheme 1). Although the reasons
for the migration in the alternative direction in these two
cases are not yet clear, the stability of the cationic species
9 could play a major role.
The epoxide mechanism was further supported by the
successful isolation of alkoxyoxiranes 6a -c (Table 1,
entries 13-15). When R * H (see Scheme 1), the
departure of the benzotriazol-1-yl group could be ac-
complished in refluxing THF. Under these conditions,
the fully substituted epoxides of type 6 from 1 (R * H)
and ketones are stable enough to be separated. Accord-
ingly, reactions of the anions of compounds 1e and 1f
with ketones, followed by refluxing in THF in the
presence of zinc bromide, with careful monitoring of the
reaction by thin layer chromatography, provided epoxides
6a -c in good yields. Compounds 6a -c showed the
expected NMR spectra and elemental analyses. The 13C
signals at ca. 91 and 70 ppm are characteristic for the
two carbons on the oxirane ring. While these fully
substituted alkoxyoxiranes 6a -c partially decomposed
on silica gel during column chromatography, they are
stable to storage at 20 °C. 2-Alkoxyoxiranes have previ-
a
Bt ) benzotriazol-1-yl; X ) R′O, R′S, or carbazol-9-yl; R ) H,
alkyl, or aryl (see Tables 1 and 2 for the designation of X, R1, R2,
and R).
derivatives 1 functioned as useful heterocycle-stabilized
acyl anion equivalents.
In the present work, the intermediates 3 thus produced
were each shown to be capable of in situ rearrangement
to afford one-carbon-homologated R-alkoxyalkyl ketones
4a -j in good to excellent yields. The structures of
products 4a -j were proved by their NMR spectroscopy
and elemental analysis data. Rearrangement was found
to be promoted by a ca. 3-fold molar excess of zinc
bromide and to occur upon heating. In accordance with
previous observations,16 zinc bromide played a vital role
in assisting the departure of the benzotriazolyl group.
As indicated in Table 1, the reaction temperatures
necessary for rearrangement vary with the nature of the
R group (Scheme 1). In the cases of 4a -g (R ) H), the
required temperature for rearrangement was much higher
than the boiling point of THF. Thus, after the reactions
of anions 2 with aldehydes and ketones, the THF was
distilled off, 1,1,2,2-tetrachloroethane was added, and the
mixture was refluxed for the time required to complete
rearrangement. In the cases of 4h -j (R ) aryl or alkyl
groups), rearrangement can be completed in refluxing
THF due to its facilitation by the aryl or alkyl groups
which stabilize the transient cations 5 (Scheme 1).
The regioselectivity of these insertions is remarkable.
In all cases (Table 1, entries 1-10), single regioisomers
4a -j were provided by migration of the group, which can
best stabilize an electron deficiency in the transition
state,23 i.e., H > Ar > alkyl; tert-alkyl > sec-alkyl >
n-alkyl. No detectable amounts of the other possible
regioisomers 7 (Scheme 1) were produced on the basis of
GCMS examination of the crude product mixtures. Sub-
stituent effects on the relative migration rates are
discussed in detail in the following paper.24
The generality of these insertions is also of special
significance in regard to the structures of both benzo-
triazole adducts and of the carbonyl compounds that can
be utilized. For benzotriazole reagents, X can be phenoxy
(25) Prakash, O.; Saini, N.; Tanwar, M. P.; Moriarty, R. M. Contemp.
Org. Synth. 1995, 121.
(26) Labadie, J . W.; Tueting, D.; Stille, J . K. J . Org. Chem. 1983,
48, 4634.
(27) J ung, M. E.; Abrecht, S. J . Org. Chem. 1988, 53, 423.
(28) Katritzky, A. R.; Yang, Z.; Lam, J . N. J . Org. Chem. 1991, 56,
6917.
(23) Hanson, J . R. (Section 3.1); Rickborn, B. (Section 3.2 and 3.3);
Coveney, D. J . (Section 3.4) In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 3, p
705.
(24) Katritzky, A. R.; Toader, D.; Xie, L. J . Org. Chem. 1996, 61,
7571.

Synthesis of R-Substituted Alkyl Ketones
J . Org. Chem., Vol. 61, No. 21, 1996 7567
ously been shown to be versatile building blocks for
organic synthesis.29 The following well-established meth-
ods for their preparation, (i) oxidation of vinyl ethers with
peroxides30,31 and (ii) reactions of R-halo ketones with dry
alcohols under basic conditions,29 are limited for the most
part to rather structurally simple 2-alkoxyoxiranes due
to the availability of the corresponding vinyl ethers and
R-halo ketones. One successful approach for the prepa-
ration of 2-alkoxyoxiranes from ketones was previously
available,32 but it involves rather complex transforma-
tions: electrolytic oxidation of ketone N-acylhydrazones
in methanolic sodium acetate, followed by thermal evolu-
tion of N2 of the intermediates 2-methoxy-∆3-1,3,4-
oxadiazolines. Our present method potentially enables
the facile construction of a wide range of fully substituted
R-alkoxyoxiranes in one-pot processes starting from
ketones.
It was expected that epoxides 6a -c would undergo
further thermal rearrangement to furnish the corre-
sponding ring-expanded or chain-extended R-alkoxyalkyl
ketones of type 4. Unfortunately, the attempted ring
expansion of cyclohexanone in the cases of entries 13 and
14 (Table 1) failed. Thus, treatment of epoxides 6a and
6b with zinc bromide upon heating in 1,1,2,2-tetrachlo-
roethane at 90 °C resulted in the recovery of the epoxides,
while heating at 120 °C gave mixtures of starting
epoxides together with small amounts of expected
R-alkoxyalkyl ketones of type 4 and heating at 140 °C
provided a complicated mixture based on GCMS analy-
ses. Similar results were obtained when 1a and 1b
reacted with cyclohexanone and cyclopentanone. We
believe the ring-expansion did occur at high temperature
(g120 °C). However, the resultant R-alkoxyalkyl ketones
with â-hydrogen were not stable under these vigorous
conditions possibly because of elimination of ethanol or
phenol to form the corresponding R,â-unsaturated ke-
tones, which again under the reaction conditions led to
other side products. When epoxide 6c was treated with
ZnBr2 in 1,1,2,2-tetrachloroethane at 110 °C, rearrange-
ment occurred immediately. However, instead of the
chain-extended ketone of type 4, the corresponding R,â-
unsaturated ketone 1,2-diphenylhept-2-en-1-one [PhCOC-
(Ph))CH(CH2)3Me] was obtained in good yield, evidently
from the initially formed 2-phenoxyketone by elimination.
Transformations of this type from carbonyl compounds
into chain-extended R,â-unsaturated ketones are being
actively explored and will be reported subsequently.
(Alk ylth io)m eth ylen e In ser tion s in to Ald eh yd es
a n d Keton es. [1-(Phenylthio)alkyl]benzotriazoles 1g,19
1j,19 and 1i33 were prepared as previously described
(Table 2). 1-[(Methylthio)methyl]benzotriazole (1h ) was
made from benzotriazole and dimethyl sulfoxide in acetic
anhydride in 60% yield and was characterized by NMR
spectra and CHN analysis. We have previously demon-
strated that 1-[(phenylthio)methyl]benzotriazole (1g)
underwent deprotonation with butyllithium and the
resulting carbanion reacted readily with aldehydes and
ketones.19 In the present work, 1-[(phenylthio)alkyl]- and
1-[(methylthio)alkyl]benzotriazoles 1g-j all underwent
deprotonation easily with n-butyllithium in THF at -78
°C. Similar to the alkoxymethylene insertions, the lithio
derivatives of 1g-j reacted with aliphatic and aromatic
aldehydes and ketones and subsequent treatment of the
intermediates with a 3-fold molar excess of zinc bromide
provided upon heating the corresponding one-carbon-
homologated R-(phenylthio)alkyl ketones 4k -s in good
yields. The migration aptitude followed the same general
trend that hydrogen migrates faster than aryl and aryl
faster than alkyl. However, as an exception, a benzyl
group migrates preferentially compared to a phenyl
group, as demonstrated by the reaction of 1-[(methylthio)-
methyl]benzotriazole (1h ) and desoxybenzoin (entry 7,
Table 2), indicating the stronger cation-stabilizing ability
of benzyl over phenyl. Each case, except for entry 7,
afforded a single regioisomer of type 4. For desoxyben-
zoin (entry 7, Table 2), both regioisomers 4q and 7q were
produced in 55% and 30% GC yields, respectively. While
4q was separated in 50% yield, 7q remained together
with a small amount of desoxybenzoin as an inseparable
mixture. Noteworthy is the fact that disubstituted
methylene groups carrying both a phenylthio group and
an aryl or alkyl group were again successfully inserted
into a carbonyl compound. Compounds 4k -s were all
characterized by 1H and 13C NMR, and novel compounds
were further confirmed by CHN analyses.
The main methods reported previously for the prepa-
ration of R-(phenylthio)alkyl ketones are based on the
reaction of regiospecifically generated enolate anions or
silyl enol ethers with various species containing an
electrophilic sulfur atom.14,34,35 They often suffer from
side reactions such as bissulfenylation. Our procedure
to one-carbon-homologated R-(phenylthio)alkyl ketones
from readily available starting materials should find use
in synthesis.
Ca r ba zolylm eth ylen e In ser tion s in to Ald eh yd es
a n d Keton es. A potential advantage of the present
methodology is its extension to introduction of other
heteroatoms concomitant with carbon insertions. Nitro-
gen is the most important of these, and we have done
some preliminary work in this area. As examples,
1-(carbazol-9-ylalkyl)benzotriazole 1k and 1l were used
successfully in the insertions. 1-(Carbazol-9-ylmethyl)-
benzotriazole (1k )36 and 1-(1-carbazol-9-ylethyl)benzo-
triazole (1l)37 were made by previous procedures. By
employing one-pot insertion procedures analogous to
those described above, one-carbon homologated R-(car-
bazol-9-yl)alkyl ketones 4t-w were obtained in 36-73%
yields and were all characterized by 1H and 13C NMR and
elemental analyses.
Con clu sion
We have shown that 1-(R-alkoxyalkyl)-, 1-[R-(alkylth-
io)alkyl]-, and 1-[R-(carbazol-9-yl)alkyl]benzotriazoles are
readily available, versatile, and high-yielding reagents
for the transformations of aldehydes and ketones into
one-carbon-homologated R-alkoxyalkyl, R-(alkylthio)alkyl,
and R-(carbazol-9-yl)alkyl ketones. Significant advan-
tages of the present one-pot methodology include its
excellent regioselectivity, the readily available starting
(29) De Kimpe, N.; De Buyck, L.; Verhe, R.; Schamp, N. Chem. Ber.
1983, 116, 3631.
(30) Hoppe, D.; Lussmann, J .; J ones, P. G.; Schmidt, D.; Sheldrick,
G. M. Tetrahedron Lett. 1986, 27, 3591.
(31) Adam, W.; Hadjiarapoglou, L.; J ager, V.; Seidel, B. Tetrahedron
Lett. 1989, 30, 4223.
(32) Chiba, T.; Okimoto, M. J . Org. Chem. 1992, 57, 1375.
(33) Katritzky, A. R.; Xie, L.; Afridi, A. S.; Fan, W.-Q.; Kuzmierk-
iewicz, W. Synthesis 1993, 47.
(34) Caputo, R.; Ferreri, C.; Palumbo, G. Synthesis 1989, 464.
(35) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J . Am. Chem. Soc. 1976,
98, 4887.
(36) Katritzky, A. R.; Yang, Z.; Lam, J . N. J . Org. Chem. 1991, 56,
2143.
(37) Katritzky, A. R.; Jurczyk, S.; Rachwal, B.; Rachwal, S.; Shcherba-
kova, I.; Yannakopoulou, K. Synthesis 1992, 1295.

7568 J . Org. Chem., Vol. 61, No. 21, 1996
Katritzky et al.
Ta ble 2. (Alk ylth io)m eth ylen e a n d Ca r ba zolylm eth ylen e In ser tion s in to Ald eh yd es a n d Keton es
111.4, 120.0, 124.3, 127.4, 127.6, 128.8, 130.9, 134.9 (2 C),
147.0. Anal. Calcd for C15H14N3OCl: C, 62.61; H, 4.90; N,
14.60. Found: C, 62.42; H, 4.69; N, 14.69.
materials, and simple procedures. However, aliphatic
cyclic ketones failed to undergo clean ring expansions,
thus demonstrating a limitation to this approach.
1-[Meth oxy(4-ch lor op h en yl)m eth yl]ben zotr ia zole (1f).
This compound was prepared by the same procedure as for
1c20 as a colorless oil (50%): 1H NMR δ 3.44 (s, 3H), 7.07 (s,
1H), 7.22-7.25 (m, 1H), 7.30-7.38 (m, 6H), 8.06-8.10 (m, 1H);
13C NMR δ 56.7, 90.3, 111.2, 120.0, 124.3, 127.3, 127.6, 128.7,
130.7, 134.5, 134.9, 146.9. Anal. Calcd for C14H12N3OCl: C,
61.43; H, 4.42; N, 15.35. Found: C, 61.47; H, 4.46; N, 15.60.
Exp er im en ta l Section
Gen er a l P r oced u r es. Melting points were determined
with a hot-stage apparatus and are uncorrected. NMR spectra
were taken in CDCl3 with tetramethylsilane as the internal
1
standard for H (300 MHz) or solvent as the internal standard
for 13C (75 MHz). Tetrahydrofuran was distilled under nitro-
gen immediately prior to use from sodium/benzophenone. All
reactions with air-sensitive compounds were carried out under
an argon atmosphere. Column chromatography was conducted
with silica gel 230-400 mesh. 1-(Methoxymethyl)benzotria-
zole (1a ),18 1-(phenoxymethyl)benzotriazole (1b),19 1-[ethoxy-
(2-chlorophenyl)methyl]benzotriazole (1c),20 1-(1-phenoxyhexyl)-
benzotriazole (1e),21 1-[(phenylthio)methyl]benzotriazole (1g),19
1-[(phenylthio)phenylmethyl]benzotriazole (1i),33 1-[1-(phen-
ylthio)ethyl]benzotriazole (1j),19 1-[(carbazol-9-yl)methyl]ben-
zotriazole (1k ),36 and 1-[1-(carbazol-9-yl)ethyl]benzotriazole
(1l)37 were prepared according to reported procedures.
1-[Eth oxy(4-ch lor op h en yl)m eth yl]ben zotr ia zole (1d ).
This compound was prepared by the same procedure as for
1c20 as a colorless oil (60%): 1H NMR δ 1.26 (t, J ) 7.1 Hz, 3
H), 3.43-3.52 (m, 1 H), 3.73-3.82 (m, 1 H), 7.18 (s, 1 H), 7.27-
7.40 (m, 7 H), 8.06-8.10 (m, 1 H); 13C NMR δ 14.6, 65.0, 88.8,
1-[(Meth ylth io)m eth yl]ben zotr ia zole (1h ). A mixture
of benzotriazole (2.4 g, 20 mmol), dimethyl sulfoxide (20 mL),
and acetic anhydride (13 mL) was stirred at 100 °C for 3 days.
The reaction mixture was poured into saturated sodium
bicarbonate aqueous solution (100 mL). To this solution were
then added sodium hydroxide (6 g) and diethyl ether (100 mL),
and the mixture was stirred overnight. The organic layer was
separated and the aqueous layer extracted with diethyl ether
(100 mL). The combined organic extracts were dried (Na2SO4),
and solvent was evaporated to give a colorless oil, which was
separated by column chromatography (hexane: Et2O ) 2:1)
to give the pure product 1h as colorless plates (60%): 1H NMR
δ 2.15 (s, 3H), 5.72 (s, 2H), 7.43 (t, J ) 8.2 Hz, 1H), 7.55 (t, J
) 8.2 Hz, 1H), 7.71 (d, J ) 8.2 Hz, 1H), 8.1 (d, J ) 8.2 Hz,
1H); 13C NMR δ 14.7, 50.7, 110.1, 120.0, 124.1, 127.4, 131.8,
146.4. Anal. Calcd for C8H9N3S: C, 53.62; H, 5.02; N, 23.50.
Found: C, 53.36; H, 5.14; H, 23.26.

Synthesis of R-Substituted Alkyl Ketones
J . Org. Chem., Vol. 61, No. 21, 1996 7569
Gen er a l P r oced u r e for th e In ser tion s in to Ald eh yd es
a n d Keton es; P r ep a r a tion of r-Alk oxya lk yl Keton es 4a -
j, r-(Alk ylth io)a lk yl Keton es 4k -s a n d 7q, r-(Ca r ba zol-
9-yl)a lk yl Keton es (4t-w ), 2-Alk oxyoxir a n es 6a -c, a n d
Ester s 8a ,b. To a solution of an appropriate benzotriazole
derivative (5 mmol) in THF (50 mL) at -78 °C under argon
was added n-BuLi (2M, 2.8 mL, 5.5 mmol). After 1 h (5 min
in the cases of 1c-f as the starting materials), a solution of
an appropriate aldehyde or ketone (5.5 mmol) in THF (10 mL)
was added. The mixture was stirred at -78 °C for an
additional 4 h and allowed to warm to room temperature
overnight. A solution of zinc bromide (15 mmol) in THF (15
mL) was then added. As indicated in Tables 1and 2, (i) the
mixture was refluxed in THF (for 4h -j, 6a -c, 4m , and 4r ) or
(ii) the THF was removed, 1,1,2-trichloroethane (for 4p , 4q,
7q, 4v, and 4w ) or 1,1,2,2-tetrachloroethane (for 4a -g, 7a ,
7b, 4k , 4l, 4n , 4o, and 4s-u ) (15 mL) added, and the mixture
refluxed. Ethyl acetate (150 mL) and diethyl ether (100 mL)
were added to the residue, and the mixture was stirred for 1
h at room temperature. The solid was filtered off, and the
solution was washed with water (2 × 100 mL) and dried
(MgSO4). After the solvent was removed, the residue was
subjected to column chromatography to give the pure product.
1-P h en yl-2-m eth oxyeth a n on e (4a ). Hexanes:ethyl ace-
tate (4:1) was used as the eluent to give a colorless oil: 1H
NMR δ 3.52 (s, 3H), 4.72 (s, 2H), 7.47 (t, J ) 7.1 Hz, 2H), 7.59
(t, J ) 7.1 Hz, 1H), 7.93 (dd, J ) 7.1 and 1.8 Hz, 2H); 13C
NMR δ 59.3, 75.1, 127.7, 128.6, 133.4, 134.7, 196.0. Anal.
Calcd for C9H10O2: C, 71.98; H, 6.71. Found: C, 71.94; H, 6.50.
1-Meth oxy-1-p h en yl-2-p r op a n on e (4b). Hexanes:ethyl
acetate (5:1) was used as the eluent to give a colorless oil: 1H
NMR δ 2.11 (s, 3H), 3.38 (s, 3H), 4.66 (s, 1H), 7.33-7.39 (m,
5H); 13C NMR δ 25.1, 57.1, 89.4, 126.9, 128.6, 128.8, 135.8,
206.6. Anal. Calcd for C10H12O2: C, 73.15; H, 7.37. Found:
C, 72.86; H, 7.30.
128.9, 129.3, 129.7, 129.9, 130.0, 133.6, 133.8, 134.2, 139.7,
194.7. Anal. Calcd for C16H14O2Cl: C, 62.15; H, 4.56.
Found: C, 62.13; H, 4.59.
10-E t h oxy-10-(4-ch lor op h e n yl)-9(10H )-p h e n a n t h r e -
n on e (4i). Hexanes:ethyl acetate (8:1) was used as the eluent
to give a white solid: mp 126-127 °C; 1H NMR δ 1.33 (t, J )
7.0 Hz, 3H), 3.25-3.34 (m, 1H), 3.53-3.63 (m, 1H), 7.10-7.15
(m, 2H), 7.21-7.26 (m, 2H), 7.33-7.58 (m, 4H), 7.64-7.69 (m,
1H), 7.93 (dd, J ) 7.8 and 1.4 Hz, 1H), 8.01-8.07 (m, 2H); 13
C
NMR δ 15.6, 61.7, 85.5, 123.1, 123.7, 128.2 (2 C), 128.4 (2 C),
128.6, 128.9, 129.4, 129.7, 131.9, 134.1, 135.0, 136.8, 138.7,
139.4, 197.3. Anal. Calcd for C22H17O2Cl: C, 75.75; H, 4.91.
Found: C, 76.10; H, 4.91.
1-(4-Meth ylp h en yl)-2-p h en oxy-1-h ep ta n on e (4j). Hex-
anes:ethyl acetate (9:1) was used as the elute to give a colorless
oil: 1H NMR δ 0.87 (t, J ) 6.8 Hz, 3H), 1.29-1.35 (m, 4H),
1.49-1.69 (m, 2H), 1.96-2.08 (m, 2H), 2.39 (s, 3H), 5.26 (dd,
J ) 8.2 and 4.7 Hz, 1H), 6.83-6.92 (m, 3H), 7.17 (d, J ) 7.4
Hz, 2H), 7.25 (d, J ) 8.3 Hz, 2H), 8.00 (d, J ) 8.3 Hz, 2H); 13
C
NMR δ 13.9, 21.6, 22.4, 25.4, 31.4, 33.4, 81.3, 115.1, 121.2,
128.9, 129.4, 129.5, 131.9, 144.5, 157.9, 198.6. Anal. Calcd
for C20H24O2: C, 81.04; H, 8.16. Found: C, 81.36; H, 8.44.
1-(4-Ch lor op h en yl)-2-(p h en ylth io)eth a n on e (4k ). Hex-
anes:ethyl acetate (4:1) was used as the eluent to give a
1
yellowish solid: mp 56-57 °C; H NMR δ 4.22 (s, 2H), 7.24-
7.32 (m, 2H), 7.37-7.40 (m, 3H), 7.42-7.45 (m, 2H), 7.86-
7.89 (m, 2H); 13C NMR δ 41.1, 127.3, 129.0, 129.1, 130.1, 130.7,
133.6, 134.3, 139.9, 192.9. Anal. Calcd for C14H11OSCl: C,
64.00; H, 4.22. Found: C, 63.99; H, 4.15.
1-P h en yl-2-(p h en ylth io)eth a n on e (4l). Hexanes:ethyl
acetate (7:1) was used as the eluent to give a yellowish solid:
mp 48-49 °C (lit.38 mp 49-50 °C); 1H NMR δ 4.27 (s, 2H),
7.21-7.46 (m, 7H), 7.55 (t, J ) 6.4 Hz, 1H), 7.93 (d, J ) 6.4
Hz, 2H); 13C NMR δ 41.1, 127.0, 128.6, 129.0, 129.1, 129.2,
130.4, 132.8, 133.4, 194.0.
1,2-Dip h en yl-2-m eth oxyeth a n on e (4c). Hexanes:ethyl
acetate (7:1) was used as the eluent to give colorless powders:
mp 46-47 °C; 1H NMR δ 3.43 (s, 3H), 5.52 (s, 1H), 7.26-7.38
1-(P h en ylt h io)-4-p h en yl-2-b u t a n on e (4m ). Hexanes:
ethyl acetate (10:1) was used as the eluent to give a colorless
oil: 1H NMR δ 2.84-2.91 (m, 4H), 3.61 (s, 2H), 7.11-7.30 (m,
10H); 13C NMR δ 29.7, 41.9, 43.9, 126.1, 126.8, 128.2, 128.4,
129.0, 129.5, 134.6, 140.6, 204.1; HRMS calcd for C16H16OS
256.0922, found 256.0935.
(m, 5H), 7.44-7.49 (m, 3H), 7.97 (dd, J ) 7.4, 1.9 Hz, 2H); 13
C
NMR δ 57.3, 86.5, 127.5, 128.4, 128.5, 128.7, 128.9, 133.1,
134.9, 136.0, 197.0. The mp as well as 1H and 13C NMR
spectra of this material were identical with those of an
authenic sample (Aldrich).
1-(4-P yr idin yl)-2-m eth oxy-2-ph en yleth an on e (4d). Hex-
anes:ethyl acetate (1:1) was used as the eluent to give a yellow
oil: 1H NMR δ 3.46 (s, 3H), 5.43 (s, 1H), 7.32-7.46 (m, 5H),
7.73 (d, J ) 6.2 Hz, 2H), 8.72 (d, J ) 6.2 Hz, 2H); 13C NMR δ
57.5, 87.1, 121.8, 127.3, 128.8, 129.0, 134.9, 140.8, 150.6, 196.8.
Anal. Calcd for C14H13NO2: C, 73.98; H, 5.77; N, 6.17.
Found: C, 74.29; H, 5.84; N, 6.10.
1-Meth oxy-4-ph en yl-2-bu tan on e (4e). Hexanes:ethyl ace-
tate (4:1) was used as the eluent to give a colorless oil: 1H
NMR δ 2.78 (t, J ) 7.5 Hz, 2H), 2.93 (t, J ) 7.5 Hz, 2H), 3.39
(s, 3H), 3.97 (s, 2H), 7.18-7.31 (m, 5H); 13C NMR δ 29.3, 40.4,
59.3, 77.8, 126.2, 128.3, 128.5, 140.8, 207.9. Anal. Calcd for
C11H14O2: C, 74.13; H, 7.92. Found: C, 73.96; H, 7.79.
1,2-Dip h en yl-2-p h en oxyeth a n on e (4f). Hexanes:ethyl
acetate (6:1) was used as the eluent to give colorless needles:
mp 84-85 °C; 1H NMR δ 6.37 (s, 1H), 6.92-6.97 (m, 3H), 7.21-
7.26 (m, 2H), 7.31-7.42 (m, 5H), 7.48 (t, J ) 7.4 Hz, 1H), 7.59
(d, J ) 7.4 Hz, 2H), 8.04 (d, J ) 7.2 Hz, 2H); 13C NMR δ 82.8,
115.7, 121.7, 127.3, 128.5, 128.7, 128.9, 129.2, 129.6, 133.5,
134.6, 135.4, 157.6, 196.0. Anal. Calcd for C20H16O2: C, 83.31;
H, 5.59. Found: C, 83.01; H, 5.52.
3-P h en oxy-4,4-d im eth yl-2-p en ta n on e (4g). Hexanes:
ethyl acetate (10:1) was used as the eluent to give a colorless
oil: 1H NMR δ 1.02 (s, 9H), 2.02 (s, 3H), 4.00 (s, 1H), 6.76 (d,
J ) 8.8 Hz, 2H), 6.89 (t, J ) 7.4 Hz, 1H), 7.18-7.23 (m, 2H);
13C NMR δ 26.4, 27.5, 35.0, 90.2, 114.7, 121.4, 129.7, 158.3,
211.2. Anal. Calcd for C13H18O2: C, 75.69; H, 8.80. Found:
C, 75.50; H, 8.96.
1-P h en yl-1-(p h en ylth io)-2-p r op en on e (4n ). Hexanes:
ethyl acetate (7:1) was used as the eluent to give white
needles: mp 67-68 °C (lit.39 mp 70 °C); 1H NMR δ 2.20 (s,
3H), 5.00 (s, 1H), 7.24-7.40 (m, 10H); 13C NMR δ 27.2, 64.5,
127.8, 128.2, 128.5, 128.9, 129.0, 132.3, 133.7, 135.5, 202.9.
1,2-Dip h en yl-2-(p h en ylth io)eth a n on e (4o). Hexanes:
ethyl acetate (7:1) was used as the eluent to give yellowish
needles: mp 72-73 °C; 1H NMR δ 5.82 (s, 1H), 7.20-7.47 (m,
12H), 7.51 (t, J ) 6.8 Hz, 1H), 7.93 (d, J ) 7.6 Hz, 2H); 13C
NMR δ 60.3, 127.9, 128.0, 128.6, 128.7, 128.8, 128.9, 133.0,
133.3, 134.0, 135.5, 135.6, 136.5, 194.7. Anal. Calcd for
C20H16OS: C, 78.92; H, 5.30. Found: C, 79.35; H, 4.97.
1-P h en yl-2-(m eth ylth io)eth a n on e (4p ). Hexanes:ethyl
acetate (20:1) was used as the eluent to give an oil: bp 112-
114 °C/0.5 mm (lit.40 bp 94-96 °C/0.3 mm); 1H NMR δ 2.49 (s,
3H), 3.78 (s, 2H), 7.48 (t, J ) 7.2 Hz, 2H), 7.59 (t, J ) 7.2 Hz,
1H), 7.99 (d, J ) 7.2 Hz, 2H); 13C NMR δ 15.9, 39.0, 128.6,
128.7, 133.3, 135.2, 194.0.
1,3-Dip h en yl-2-(m eth ylth io)-1-p r op a n on e (4q). Hex-
anes:ethyl acetate (20:1) was used as the eluent to give
1
colorless plates: mp 57-58 °C; H NMR δ 2.02 (s, 3H), 3.08
(dd, J ) 14.0, 6.3 Hz, 1H), 3.46 (dd, J ) 14.0, 8.4 Hz, 1H),
4.41 (dd, J ) 6.3, 8.4 Hz, 1H), 7.18-7.29 (m, 5H), 7.43 (d, J )
7.2 Hz, 2H), 7.52 (t, J ) 7.2 Hz, 1H), 7.94 (d, J ) 7.2 Hz, 2H);
13C NMR δ 11.4, 35.3, 47.6, 126.5, 128.3, 128.4, 128.5, 129.1,
133.0, 135.9, 138.8, 193.8. Anal. Calcd for C16H16OS: C, 74.96;
H, 6.29. Found: C, 75.21; H, 6.46.
1,2-Dip h en yl-2-(p h en ylth io)eth a n on e (4r ). Hexanes:
ethyl acetate (5:1) was used as the eluent to give yellowish
2-E t h oxy-1-(4-ch lor op h en yl)-2-(2-ch lor op h en yl)et h a -
n on e (4h ). Hexanes:ethyl acetate (5:1) was used as the eluent
to give a colorless oil: 1H NMR δ 1.28 (t, J ) 7.0 Hz, 3H),
3.57-3.73 (m, 2H), 6.10 (s, 1H), 7.23-7.26 (m, 2H), 7.36-7.44
(m, 4H), 7.90-7.94 (m, 2H); 13C NMR δ 15.2, 65.8, 79.8, 127.5,
(38) Padmanabhan, S.; Ogawa, T.; Suzuki, H. Bull. Chem. Soc. J pn.
1989, 62, 1358.
(39) Morel, G.; Marchand, E.; Foucaud, A. Synthesis 1980, 918.
(40) Prelog, V.; Hahn, V.; Brauchli, H.; Beyerman, H. C. Helv. Chim.
Acta 1944, 27, 1209.

7570 J . Org. Chem., Vol. 61, No. 21, 1996
Katritzky et al.
(m, 4H), 7.81 (d, J ) 7.1 Hz, 2H), 8.06 (d, J ) 8.1 Hz, 2H); 13
NMR δ 14.1, 54.7, 109.1, 119.6, 120.5, 123.7, 126.1, 128.0,
128.5, 133.3, 135.3, 139.2, 198.0; HRMS calcd for C21H17NO
300.1388 (M + 1), found 300.1362.
needles: mp 72-73 °C; 1H NMR δ 5.86 (s, 1H), 7.20-7.46 (m,
12H), 7.52 (t, J ) 6.8 Hz, 1H), 7.94 (d, J ) 7.6 Hz, 2H); 13C
NMR δ 60.3, 127.9, 128.0, 128.5, 128.6, 128.7, 128.8, 128.9,
133.1, 133.3, 134.1, 135.7, 136.5, 194.7. Anal. Calcd for
C20H16OS: C, 78.92; H, 5.30. Found: C, 79.36; H, 4.97.
1-P h en yl-2-(p h en ylth io)-1-p r op a n on e (4s). Chloroform
was used as the eluent to give a colorless oil: 1H NMR δ 1.50
(d, J ) 6.8 Hz, 3H), 4.62 (q, J ) 6.8 Hz, 1H), 7.22-7.29 (m,
3H), 7.33-7.36 (m, 2H), 7.40-7.45 (m, 2H), 7.51-7.57 (m, 1H),
7.94 (d, J ) 7.1 Hz, 2H); 13C NMR δ 17.0, 46.2, 127.9, 128.5,
128.6, 128.8, 129.0, 133.0, 134.4, 135.7, 196.2. The 1H NMR
spectrum is in agreement with the reported data.41
1-(4-Ch lor op h en yl)-2-(ca r ba zol-9-yl)eth a n on e (4t). The
crude material was recrystallized from hexane and ethyl
acetate to give yellowish needles: mp 212-213 °C; 1H NMR δ
6.20 (s, 2H), 7.29 (t, J ) 8.4 Hz, 2H), 7.47 (t, J ) 8.4 Hz, 2H),
7.58 (d, J ) 8.4 Hz, 2H), 7.76 (d, J ) 8.4 Hz, 2H), 8.23-8.28
(m, 4H); 13C NMR δ 49.2, 109.3, 118.9, 120.0, 122.3, 125.5,
128.9, 130.1, 133.5, 138.9, 140.7, 193.2. Anal. Calcd for
C20H14NOCl: C, 75.22; H, 4.42; N, 4.39. Found: C, 75.56; H,
4.46; N, 4.32.
C
(1-P h en oxyh exylen e)cycloh exa n e Ep oxid e (6a ). Hex-
anes:ethyl acetate (5:1) was used as the eluent to give a
colorless oil: 1H NMR δ 0.82-0.90 (m, 3H), 1.22-1.31 (m, 4H),
1.44-1.79 (m, 13H), 2.07-2.17 (m, 1H), 6.95-7.04 (m, 3H),
7.23-7.30 (m, 2H); 13C NMR δ 13.8, 22.4, 24.2, 24.4, 25.6, 28.7,
29.6, 30.2, 31.5, 67.3, 91.2, 117.6, 121.7, 129.3, 155.1; HRMS
calcd for C18H26O2 275.2011 (M + 1), found 275.2018.
[Meth oxy(4-ch lor op h en yl)m eth ylen e]cycloh exa n e Ep -
oxid e (6b). Hexanes:ethyl acetate (4:1) was used as the eluent
to give a colorless oil: 1H NMR δ 1.11-1.36 (m, 3H), 1.41-
1.67 (m, 4H), 1.76-1.88 (m, 2H), 1.93-2.01 (m, 1H), 3.21 (s,
3H), 7.35-7.45 (m, 4H); 13C NMR δ 24.6, 25.1, 25.6, 29.9, 30.1,
52.5, 71.5, 91.4, 128.3, 129.4, 133.3, 134.3. Anal. Calcd for
C14H17O2Cl: C, 66.53; H, 6.78. Found: C, 66.43; H, 6.85.
1,1-Dip h en yl-2-p h en oxyh ep t-1-en e Ep oxid e (6c). Hex-
anes:ethyl acetate (9:1) was used as the eluent to give a
colorless oil: 1H NMR δ 0.74 (t, J ) 7.1 Hz, 3H), 1.02-1.12
(m, 4H), 1.43-1.53 (m, 3H), 2.03-2.10 (m, 1H), 6.97 (t, J )
7.3 Hz, 1H), 7.05 (d, J ) 7.7 Hz, 2H), 7.20-7.40 (m, 8H), 7.49-
7.53 (m, 4H); 13C NMR δ 13.7, 22.1, 23.7, 29.6, 31.3, 70.4, 91.6,
118.3, 122.3, 127.2, 127.4, 127.7, 127.8, 127.9, 128.3, 129.2,
137.6, 138.1, 154.8. Anal. Calcd for C25H26O2: C, 83.75; H,
7.53. Found: C, 83.81; H, 7.53.
1-(Meth oxyca r bon yl)in d a n (8a ). Hexanes:ethyl acetate
(5:1) was used as the eluent to give a colorless oil: 1H NMR δ
2.27-2.51 (m, 2H), 2.87-2.97 (m, 1H), 3.06-3.16 (m, 1H), 3.73
(s, 3H), 4.06 (dd, J ) 8.0, 7.7 Hz, 1H), 7.15-7.27 (m, 3H), 7.36-
7.39 (m, 1H); 13C NMR δ 28.7, 31.7, 50.1, 51.9, 124.6, 124.7,
126.4, 127.5, 140.6, 144.1, 174.3. Anal. Calcd for C11H12O2:
C, 74.96; H, 6.87. Found: C, 74.80; H, 6.49.
Meth yl 4-P h en yl-3-bu ten oa te (8b). Hexanes: methylene
chloride (2:1) was used as the eluent to give a colorless oil:
1H NMR δ 3.17 (dd, J ) 7.0, 1.3 Hz, 2H), 3.64 (s, 3H), 6.62
(dt, J ) 15.9, 7.0 Hz, 1H), 6.42 (d, J ) 15.9 Hz, 1H), 7.15-
7.31 (m, 5H); 13C NMR δ 38.2, 51.9, 121.6, 126.3, 127.5, 128.5,
133.5, 136.8, 172.0. Anal. Calcd for C11H12O2: C, 74.98; H,
6.86. Found: C, 74.60; H, 6.82.
1-P h en yl-2-(ca r ba zol-9-yl)eth a n on e (4u ). Chloroform
was used as the eluent to give yellowish needles: mp 210-
1
212 °C; H NMR δ 6.11 (s, 2H), 7.21 (t, J ) 8.1 Hz, 2H), 7.39
(t, J ) 8.1 Hz, 2H), 7.50 (d, J ) 8.1 Hz, 2H), 7.59-7.64 (m,
2H), 7.73 (t, J ) 7.6 Hz, 1H), 8.14-8.19 (m, 4H); 13C NMR δ
49.2, 109.2, 118.8, 120.0, 122.3, 125.5, 128.1, 128.7, 133.7,
134.8, 140.7, 194.0; HRMS calcd for C20H15NO 285.1154, found
285.1131.
1-(Ca r ba zol-9-yl)-1-p h en yl-2-p r op a n on e (4v). Hexanes:
ethyl acetate (8:1) was used as the eluent to give colorless
1
plates: mp 142-143 °C; H NMR δ 2.04 (s, 3H), 6.38 (s, 1H),
7.15-7.42 (m, 11H), 8.16 (d, J ) 7.5 Hz, 2H); 13C NMR δ 28.0,
66.7, 109.7, 120.1, 120.6, 123.7, 126.2, 127.8, 128.1, 128.4,
133.5, 140.2, 203.4; HRMS calcd for C21H17NO 300.1388 (M +
1), found 300.1392.
1-P h en yl-2-(ca r ba zol-9-yl)-1-p r op a n on e (4w ). Hexanes:
ethyl acetate (4:1) was used as the eluent to give a colorless
oil: 1H NMR δ 1.78 (d, J ) 6.8 Hz, 3H), 6.04 (q, J ) 6.8 Hz,
1H), 7.14-7.26 (m, 4H), 7.31 (t, J ) 7.1 Hz, 1H), 7.44-7.48
(41) Blatcher, P.; Warren, S. J . Chem. Soc., Perkin Trans. 1 1979,
1074.
J O960840P