Transformations of N-Substituted Benzotriazoles into the Corresponding Carbanions by C-Benzotriazole Bond Scission

Article abstract of DOI:10.1021/jo962246l

Various TV-substituted benzotriazoles are transformed, by scission of the C-benzotriazole bond, into the corresponding carbanions by treatment with lithium. Thus, N-(diphenylmethyl)benzotriazole (1), N-benzylbenzotriazole (6), and N-allylbenzotriazole (10) all gave carbanions that reacted with diverse electrophiles to afford the corresponding products in good yields. This new methodology was successfully utilized to convert N-benzylbenzotriazole (6) and N-allylbenzotriazole (10) into dianion synthons by a sequential lithiation and reductive coupling and bis(benzotriazolyl)toluene (18) by double reductive couplings, demonstrating the synthetic potential of the present methodology.

Full text of DOI:10.1021/jo962246l

4
116
J . Org. Chem. 1997, 62, 4116-4120
Tr a n sfor m a tion s of N-Su bstitu ted Ben zotr ia zoles in to th e
Cor r esp on d in g Ca r ba n ion s by C-Ben zotr ia zole Bon d Scission
‡
Alan R. Katritzky* and Ming Qi
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received December 3, 1996X
Various N-substituted benzotriazoles are transformed, by scission of the C-benzotriazole bond, into
the corresponding carbanions by treatment with lithium. Thus, N-(diphenylmethyl)benzotriazole
(1), N-benzylbenzotriazole (6), and N-allylbenzotriazole (10) all gave carbanions that reacted with
diverse electrophiles to afford the corresponding products in good yields. This new methodology
was successfully utilized to convert N-benzylbenzotriazole (6) and N-allylbenzotriazole (10) into
dianion synthons by a sequential lithiation and reductive coupling and bis(benzotriazolyl)toluene
(18) by double reductive couplings, demonstrating the synthetic potential of the present methodology.
In tr od u ction
Sch em e 1
Scissions of various C-X bonds (C-halogen, C-chal-
cogen, and C-P) with the loss of the heteroatom func-
tionality and formation of the corresponding carbanion
1
are well documented. However, the few examples of
transformations of C-N bonds into carbanions reported
by Yus et al.2 all involve reductive ring opening of
2
a,b
nitrogen-containing heterocycles, such as aziridines
or
azetidines,2 and take advantage of the high ring strain
of these heterocycle rings. The conversion of acyclic C-N
bonds into the corresponding carbanions by C-N scission
has not previously been achieved.
c
Sch em e 2a
In the past decade, our group has extensively investi-
gated the use of the benzotriazolyl group (Bt) as an
efficient leaving group.3 Previous synthetic applications
of benzotriazole chemistry have explored the now well-
recognized ability of the benzotriazole group to stabilize
both R-carbocations (Scheme 1, route a) and R-carbanions
(
route b) and, in addition, to act as a good leaving group
route c). In almost all cases where benzotriazole has
(
acted as a leaving group it has behaved as a nucleofuge
producing a carbocation as a reactive intermediate.3 The
only exception so far reported was that [R-(dialkylami-
no)alkyl]benzotriazoles could afford R-amino radicals.4
Our previous experience prompted us to utilize N-
substituted benzotriazoles as the substrate to transform
acyclic C-N bonds into the corresponding carbanions.
Herein, we disclose novel transformations of benzotria-
zole derivatives directly into the corresponding carban-
a
+
Method A: (i) Li, E , THF, -78 °C, 2 h, (ii) H2O. Method B:
+
(
i) Li, THF, -78 °C, 1 h, (ii) E , 30 min, (iii) H2O.
ions (Scheme 1, route d) when treated with lithium in
tetrahydrofuran and demonstrate the considerable syn-
thetic utility of trapping these intermediates.
‡
Part of this work has been presented at the 212th ACS National
Meeting by M. Qi, Orlando, FL, Aug 1996.
Resu lts a n d Discu ssion
X
Abstract published in Advance ACS Abstracts, May 1, 1997.
(
1) (a) McCombie, S. W. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pregamon Press: Oxford, 1991; Vol. 8, p 811.
b) Gray, M.; Tinkl, M.; Snieckus, V. In Comprehensive Organometallic
1
-(Diphenylmethyl)benzotriazole (1a ) was first em-
ployed as a substrate to transform the C-Bt bond into
the corresponding carbanion. When compound 1a was
reacted with lithium in the presence of propionaldehyde
in THF (Barbier-type reaction conditions) under argon
at 0 °C (Scheme 2), only three compounds were detected
from the reaction mixture by GC/MS (Table 1, entry 1).
They were separated and characterized as diphenyl-
methane (2), 1,1-diphenyl-2-butanol (3a ), and N-(diphen-
ylmethyl)aniline (4) by H and C NMR. Compound 3a
was the product expected from the reaction of an inter-
mediate carbanion and propionaldehyde. After a variety
of reaction conditions were attempted, we found that it
was possible to eliminate byproducts 4 from the reaction
(
Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;
Pergamon: Oxford, 1995; Vol. 11, pp 1. (c) Williams, J . O.; Kelly, M.
J . In Comprehensive Organic Functional Group Transformations;
Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.; Elsevier Science
Inc.: New York, 1995; Vol. 1, pp 843.
(2) (a) Almena, J .; Foubelo, F. and Yus, M. Tetrahedron Lett. 1993,
3
3
4, 1649. (b) Almena, J .; Foubelo, F.; Yus, M. J . Org. Chem. 1994, 59,
210. (c) Almena, J .; Foubelo, F.; Yus, M. Tetrahedron 1994, 50, 5775.
d) Almena, J .; Foubelo, F.; Yus, M. Tetrahedron 1996, 52, 8545.
(
(
3) (a) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron
1
13
1
3
991, 47, 2683. (b) Katritzky, A. R.; Lan, X. Chem. Soc. Rev. 1994,
63. (c) Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis 1994, 445. (d)
Katritzky, A. R.; Yang, Z.; Cundy, D. J . Aldrichim. Acta 1994, 27, 31.
4) (a) Aurrecoechea, J . M.; Fern a´ ndez-Acebes, A. Tetrahedron Lett.
992, 33, 4763. (b) Aurrecoechea, J . M.; Fern a´ ndez-Acebes, A.
Tetrahedron Lett. 1993, 34, 549.
(
1
S0022-3263(96)02246-3 CCC: $14.00 © 1997 American Chemical Society

Transformations of N-Substituted Benzotriazoles
J . Org. Chem., Vol. 62, No. 12, 1997 4117
Sch em e 3a
Ta ble 1. Rea ction s of 1a w ith Lith iu m a n d
P r op ion a ld eh yd e u n d er Va r iou s Con d ition s
GC/MS
b
yield (%)
3a
16 52 32
T
(°C)
entry
reagents
methoda
solvent
THF
THF
PhH-HMPA
THF
2
4
1
2
3
4
5
6
Li
Li
Li
Li
A
A
A
A
A
B
0
-20 31 52 <3
20 34
8
44
0
0
-78 19 72
-78 30 58
-78 28 50
Li/cat. DTBB
Li
THF
THF
0
a
Method A: compound 1a reacted with lithium in the presence
of propionaldehyde. Method B: compound 1a was treated with
lithium (1 h) before being quenched by the aldehyde. b GC/MS
yields were taken directly from the GC/MS report. In most cases,
the reaction mixtures contain a small amount of other compounds
like benzeneamine.
a
Key: (a) Li, (CH2)5CO, 88%; (b) BuLi; (c) BuBr; (d) Li, EtCOEt,
80%; (e) Li, PhCO2Me, 46%.
Sch em e 4a
Ta ble 2. Rea ction s of (Dip h en ylm eth yl)ben zotr ia zole (1)
w ith Electr op h iles
yielda
electrophile
CH CH CHO
method product
E
(%) charact
3
2
A
A
A
A
B
A
A
B
B
B
3a
3b
3c
3d
3d
3e
3f
CH
(CH
CH
3
CH
2
CH(OH)
) C(OH)
2 5
65
85
b
c
c
b
b
b
b
b
b
c
(CH
2
)
5
CO
CH
3
(CH
2
)
7
CHO
3
(CH
2
)
7
CH(OH) 65
PhCHO
PhCHO
PhCH(OH)
PhCH(OH)
40
45
85
67
60
95
Me
3
SiCl
SiMe
3
PhCO
PhCH
MeI
2
Me
Br
PhCO
PhCH
Me
2
3g
3h
2
d
e
PhCH:NH(Ph)
3i
PhCHNH(Ph)
48
a
Key: (a) Li, (CH2)5CO, 82%; (b) BuLi; (c) BuBr; (d) Li, EtCOEt,
a
Isolated yield. b Known compounds, for characterization see
73%; (e) MeI; (f) Li, (CH2)5CO, 60%.
c
Experimental Section. Novel compounds, which were character-
ized by H and C NMR spectroscopy and provided satisfactory
elemental analyses (for details see the Supporting Information).
A mixture of compounds 2, 3h , and 5 was obtained (see text).
An imine dimer was also isolated (see Experimental Section).
1
13
pared to aliphatic carbonyl compounds; a similar result
was obtained when the two-step procedure was at-
tempted (Table 2). The reaction of compound 1 with
methyl benzoate gave the corresponding ketone 3f in good
yield, together with a trace (2% GC) of 1,2,2-triphenyl-
ethanol, evidently formed by the reduction of ketone 3f
by excess lithium.
d
e
by lowering the reaction temperature (Table 1, entries 2
and 4). However, the second byproduct, diphenyl-
methane (2), was more difficult to avoid. Although
replacing THF as solvent by benzene-HMPA can decrease
The method B two-step process was applied when
benzyl or alkyl halides were used as electrophiles. The
reaction of compound 1 with benzyl bromide afforded
5
the rate of hydrogen abstraction by radicals, in the
present case, higher yields for 2 and 4 but a lower yield
for expected product 3a resulted in using benzene-
HMPA as solvent. One-step reaction conditions (method
A) work better than the two-step procedure (Table 1,
entries 4 vs 6). Also, lithium metal alone gave better
results than by using 4,4′-di-tert-butylbiphenyl (DTTB)
as a catalyst (Table 1, entries 4 vs 5). Benzotriazole rings
probably assist the electron transfer in these reactions.
No significant difference in the product slate was found
on using 2-(diphenylmethyl)benzotriazole (1b) as starting
material instead of the 1-isomer 1a . Therefore, the
mixture of the 1- and 2-(diphenylmethyl)benzotriazoles
1
,1,2-triphenylethane (3g) in good yield (Table 2). Excess
lithium present in the reaction media converted a part
of benzyl bromide to 1,2-diphenylethane (40% GC), as
established by GC/MS. The reaction of compound 1 with
methyl iodide gives a mixture of the methylated and
dimethylated products, i.e., 1,1-diphenylethane (3h ) (30%)
and 2,2-diphenylpropane (5) (44%), contaminated with
diphenylmethane (2) (21%) in 95% total isolated yield.
The dimethylated product could be formed from 3h via
further lithiation and methylation. The addition reaction
of the preformed carbanion with the imine N-benzyli-
deneaniline afforded amine 3i, accompanied by the imine
dimer, N,N',1,2-tetraphenylethylenediamine.
(
1), which could be easily and quantitatively prepared
from diphenylmethanol, was used in subsequent reac-
tions.
6
N-Benzyl- (6) and N-allylbenzotriazoles (10) also re-
acted with cyclohexanone to give high yields of 1-ben-
zylcyclohexanol (7) (Scheme 3) and 1-allylcyclohexanol
A variety of different classes of electrophiles worked
well either under the conditions of method A or by using
a two-step process (method B, Scheme 2). The results
are summarized in Table 2. Small amounts of the pinacol
coupling product were detected by GC/MS in the reaction
of cyclohexanone. A low yield of an alkene was found in
the GC/MS spectrum of the product of the nonanal
reaction. Benzaldehyde gave a lower yield (40%) com-
(11) (Scheme 4) using the reaction conditions of method
A. However, the simple alkyl-substituted N-pentylben-
zotriazole could not be converted into the corresponding
pentyllithium under the above conditions.
When samarium diiodide was used instead of lithium,
it converted only part of N-(diphenylmethyl)benzotriazole
(
5) Kunishima, M.; Hioki, K.; Ohara, T.; Tani, S. J . Chem. Soc.,
Chem. Commun. 1992, 219.
6) Katritzky, A. R.; Perumal, S.; Fan, W.-Q. J . Chem. Soc., Perkin
Trans. 2 1990, 2059.
(1) into diphenylmethane (2). The reaction of N-allyl-
benzotriazole (10) and cyclohexanone also gave a very
low yield of the product 11.
(

4
118 J . Org. Chem., Vol. 62, No. 12, 1997
Katritzky and Qi
Sch em e 5
Sch em e 6a
a
Key: (a) BtH, SOCl2, see ref 15; (b) Li/LiBr, Et2CO.
demonstrated that two electrophiles can be introduced
into these compounds by the technique of sequential
lithiation and reductive coupling.
N-Benzylbenzotriazole (6) (Scheme 3) was lithiated by
butyllithium; the resulting carbanion reacted almost
quantitatively with butyl bromide to form intermediate
8
. To introduce the second electrophile, intermediate 8
was treated in situ with lithium in the presence of
-pentanone or methyl benzoate. The expected products
3
alcohol 9a and ketone 9b were isolated in 80% and 46%
overall yields, respectively.
These reactions may involve single-electron transfer
(
SET) from lithium to compounds 1, 6, or 10 to form the
In a similar manner, N-allylbenzotriazole (10) (Scheme
4) was treated with butyllithium and trapped with butyl
bromide or iodomethane to afford intermediates 12a ,b,
which were then each further treated with lithium and
a ketone. Homoallylic alcohols 13a ,b were thus obtained
by one-pot reactions from the simple starting material
10 in 73% and 60% overall yields, respectively. Most
importantly, compound 12a ,b reacted with the ketones
exclusively at the R-position. No product of γ-attack
could be detected from the GC/MS spectra of the reaction
mixture.
corresponding radical anions (e.g., 14, Scheme 5). The
intermediate 14 could lose a proton radical affording a
carbanion 15 when the reaction temperature is higher
than -20 °C or lose a benzotriazolyl anion forming
diphenylmethyl radical 16. The carbanion 15 can convert
to byproduct 4 through the ring opening of benzotriazole
and further reduction. On the other hand, the diphen-
ylmethyl radical 16 could be further reduced to diphen-
ylmethyl anion 17 by a second SET process or abstract a
hydrogen from THF give another byproduct 2. Byprod-
7
8
9
uct 2 could also be formed from anion 17 by abstracting
The umpolung of benzaldehyde to a toluene dianion
synthon (previously effected using selenium methodol-
a proton from carbonyl compounds10 or THF.
11
Both
1
4
intermediates radical 16 and carbanion 17 could be
reacted with electrophiles to afford the expected products.
It is probably the carbanion, rather than the radical, that
reacts with the electrophile to form the products. If the
last step involved reaction of radicals, the aromatic
carbonyl compounds should have given better results
than their aliphatic analogues because it has previously
been shown that the former are more easily reduced to
ketyls and coupled with the radical.12 The absence of
diphenylmethyl or benzyl radical dimer in the GC/MS
reaction mixture spectra supports our proposed reaction
mechanism.
Syn th etic P oten tia l of Th is New Meth od ology.
N-Benzyl- and N-allylbenzotriazoles can be lithiated at
the R-carbon and the intermediates reacted with elec-
trophiles to afford various classes of substituted benzo-
triazoles.13 However, no convenient method was previ-
ously available for removing the Bt moiety. We have now
ogy ) was achieved in two steps (Scheme 6): benzalde-
hyde was first converted to bis(benzotriazolyl)toluene 18
as previously reported,15 and 18 was reacted with an
electrophile in the presence of excess lithium in THF. In
the second step, the two C-Bt bonds were sequentially
transformed into carbanions and reacted with 3-pen-
tanone as electrophile to give 1,3-diol 19 in 60% yield.
3-Benzyl-3-pentanol (20), the reductive product of the
first reductive coupling intermediate 21 (Scheme 6), was
detected by GC/MS and isolated as the only byproduct.
In conclusion, we found that easy scission of carbon-
nitrogen bonds R-Bt allows transformation of benzo-
triazole derivatives into carbanions. As is well docu-
mented,3 diverse benzotriazole derivatives are easily
prepared and are of considerable use as synthetic inter-
mediates. However, previous benzotriazole methodology
has required substituent activation for effective removal
of the benzotriazole moiety. The new transformations
presented here offer advantageous benzotriazole removal
for unactivated derivatives and further demonstrate the
value of benzotriazole as a synthetic auxiliary as well as
an alternative way to prepare a variety of lithium
reagents.
(
(
7) Katritzky, A. R.; Lan, X.; Lam, J . Chem. Ber. 1991, 124, 1431.
8) Eisch, J . J .; Kaska, D. D.; Peterson, C. J . J . Org. Chem. 1966,
3
1, 453.
(9) Matsukawa, M.; Inanaga, J .; Yamaguchi, M. Tetrahedron Lett.
1
987, 28, 5877.
(10) (a) Tsunoda, T.; Fujiwara, K.; Yamamoto, Y.; It oˆ , S. Tetrahedron
Lett. 1991, 32, 1975. (b) Guijarro, D.; Yus, M. Tetrahedron 1993, 49,
7
761.
(14) For a recent example of the geminal difunctionalization of the
carbonyl carbon of carbonyl compounds via selenides, see: Kreif, A.;
Nazih, A. Tetrahedron Lett. 1995, 36, 8115.
(11) Broka, C. A.; Shen, T. J . Am. Chem. Soc. 1989, 111, 2981.
12) Curran, D. P.; Totleben, M. J . J . Am. Chem. Soc. 1992, 114,
(
6
050.
(15) Katritzky, A. R.; Kuzmierkiewicz, W.; Rachwal, B.; Rachwal,
S.; Thomson, J . J . Chem. Soc., Perkin Trans. 1 1987, 811.
(16) Krollpfeiffer, F.; P o¨ tz, H.; Rosenberg, A. Ber. Dtsch. Chem. Ges.
A 1938, 71, 596.
(13) (a) Katritzky, A. R.; Li, J .; Malhotra, N. Liebigs Ann. Chem.
1
992, 843. (b) Katritzky, A. R.; Gordeev, M. F.; Greenhill, J . V.; Steel,
P. J . J . Chem. Soc., Perkin Trans. 1 1992, 1111.

Transformations of N-Substituted Benzotriazoles
J . Org. Chem., Vol. 62, No. 12, 1997 4119
Exp er im en ta l Section
H, t, J ) 7.4 Hz), 7.05-7.25 (11 H, m), 5.36 (1 H, dd, J ) 8.8,
1
3
3
.0 Hz), 4.23 (1 H, d, J ) 8.8 Hz), 2.16-2.18 (1 H, m);
C
Melting points were measured on a hot-stage microscope
NMR δ 142.2, 141.5, 140.9, 128.9, 128.7, 128.6, 128.2, 128.0,
1
13
and are uncorrected. H and C NMR data were collected on
a 300 NMR spectrometer (300 and 75 MHz, respectively) with
1
27.5, 126.8, 126.3, 76.7, 60.2.
2
0
Tr im eth yl(d ip h en ylm eth yl)sila n e (3e): white solid; mp
3
TMS as internal reference in CDCl . All mass spectra were
1
7
7
1
1
2-74 °C (lit.20 mp 73-75 °C); H NMR δ 7.21-7.28 (8 H, m),
determined on a HP5890 Series II capillary GC operating in
split mode with helium carrier gas and fitted with a mass
selective detector (MSD). The column used was an HP5
capillary column 30 m × 0.25 mm, with 0.25 µm film thickness
of 5% phenyl methyl silicone gum. The temperature program
used an initial temperature of 50 °C for 1 min and then ramped
1
3
.10-7.16 (2 H, m), 3.51 (1 H, s), 0.03 (9 H, s); C NMR δ
+
42.9, 128.7, 128.3, 125.0, 46.1, -1.7; MS m/z 240 (M , 20),
65 (23), 73 (100).
1
9
1
,2,2-Tr ip h en yleth a n on e (3f): white solid; mp 134-135
19 1
°
C (lit. mp 133-134 °C); H NMR δ 8.03 (2 H, d, J ) 7.5
Hz), 7.53 (2 H, t, J ) 6.9 Hz), 7.25-7.45 (11 H, m), 6.07 (1 H,
-
1
at 10 °C min to 250 °C. The GC yield was determined by
integration areas of all the ions from GC/MS. Column chro-
matography was carried out using 230-400 mesh silica.
Compounds 1a and 1b were prepared as a mixture from
benzotriazole, diphenylmethanol, and a catalytic amount of
PTS in refluxing benzene, using a Dean-Stark trap to remove
s); 13C NMR δ 198.2, 139.1, 133.0, 129.9, 129.2, 129.0, 128.7,
+
1
28.6, 128.4, 127.1, 59.4; MS m/z 272 (M , 0.5), 167 (34), 105
(
100).
1
,2,2-Tr ip h en yleth a n e (3g):19 white solid; mp 53-54 °C
1
(
lit.19 mp 54 °C); H NMR δ 7.07-7.25 (13 H, m), 6.98 (2 H, d,
the formed water, in quantitative yield. N-Benzyl-6 and
6
J ) 6.3 Hz), 4.22 (1 H, t, J ) 7.8 Hz), 3.35 (2 H, d, J ) 7.9
Hz); 13C NMR δ 144.4, 140.2, 129.0, 128.3, 128.2, 128.0, 126.2,
1
6
N-allylbenzotriazoles were prepared from benzotriazole with
benzyl bromide or allyl bromide, and potassium hydroxide in
refluxing benzene or ethanol, both in greater than 90% yields.
+
1
25.9, 53.1, 42.1. MS m/z 258 (M , 0.5), 167 (100).
1
7
17
Dip h en ylm eth a n e (2), 1,1-d ip h en yleth a n e (3h ), and
1
2
,2-d ip h en ylp r op a n e (5):21 light yellow syrup; H NMR δ
Compound 18 was prepared from benzotriazole, thionyl chlo-
ride, and benzaldehyde in 75% yield.15 All these benzotriazole
7.14-7.30 (10 H, m), 4.14 (1 H, q, J ) 7.4 Hz, 3h ), 3.97 (2 H,
s, 2), 1.67 (6 H, s, 5), 1.63 (3 H, d, J ) 7.3 Hz, 3h ); C NMR
δ 150.6 (5), 146.3 (3h ), 140.8 (2), 128.9, 128.4, 128.3, 128.0,
1
(
1
13
derivatives were used directly (without further purification)
from the above reactions in the experiments now described.
All other starting materials were supplied by Aldrich Chemical
Co. or Fisher and used without further purification.
Gen er a l P r oced u r e for th e Rea ction s of Com p ou n d s
, 6, or 10 w ith Lith iu m a n d Electr op h iles. Meth od A.
Lithium (0.57 g, 25 mmol, 30% dispersion in mineral oil, low
content of sodium <0.05%) was washed twice with THF under
argon. THF (5 mL) was added, and the suspension was cooled
to -78 °C. A solution of the appropriate benzotriazole deriva-
tives (5 mmol) and electrophiles (7.5 mmol) in THF (25 mL)
was added dropwise to the lithium suspension over 1 h and
kept another hour before being quenched with water (15 mL)
at the same temperature. The reaction mixture was sepa-
rated, and the aqueous phase was extracted with diethyl ether
27.6, 126.8, 126.0, 125.6, 44.8 (3h ), 42.9 (5), 41.9 (2), 30.7
5), 21.8 (3h ); MS m/z for 2, 168 (M , 94), 167 (100); for 3h ,
82 (M , 33), 167 (100); for 5, 196 (M , 22), 181 (100), 166
+
+
+
(19).
1
N,1,2,2-Tetr a p h en yleth yla m in e (3i): white solid; mp
1
1
77-179 °C; H NMR δ 7.21-7.30 (5 H, m), 6.99-7.16 (12 H,
m), 6.61 (1 H, t, J ) 7.2 Hz), 6.42 (2 H, d, J ) 7.6 Hz), 4.98 (1
H, d, J ) 8.7 Hz), 4.23 (1 H, d, J ) 8.8 Hz), 4.15 (1 H, br s);
1
3
C NMR δ 147.1, 142.3, 141.9, 140.5, 129.0, 128.7, 128.2,
1
28.0, 127.4, 127.0, 126.9, 126.4, 117.5, 113.6, 61.4, 59.6. Anal.
Calcd for C26
H, 6.85; N, 3.96.
N,N′,1,2-Tetr a p h en yleth ylen ed ia m in e: yellow solid; mp
H23N: C, 89.36; H, 6.63; N, 4.01. Found: C, 89.57;
8
8
1
(
2 × 20 mL). The combined organic extracts were washed with
137-142 °C (lit. mp 134-140 °C); H NMR (CDCl
3
-D O) δ
2
saturated NaCl solution, dried, and evaporated to give the
crude product, which was purified by flash column chroma-
tography (eluent: hexanes-ethyl acetate) to afford the pure
product.
(two isomers in a ratio of 1.5:1, peaks in minor isomer in
square brackets) 6.92-7.23 (14 H, m), 6.62-6.68 (2 H, m),
6.48-6.52 (4 H, m), 4.53 (4 H, s) [4.95 (s)]; 13C NMR: δ 147.0
[146.5], 139.9 [138.2], 129.1 [129.2], 128.4 [128.2], 127.5
[127.3], 118.1 [117.8], 114.1 [113.7], 64.0 [62.0]. Anal. Calcd
Meth od B. The same procedure was applied except that
lithium was first treated with compound 1 (1 h) before being
trapped by the electrophile (30 min).
for C26
24 2
H N : C, 85.68; H, 6.64; N, 7.69. Found: C, 85.91; H,
6.77; N, 7.57.
1
7
1-Ben zylcycloh exa n ol (7):22 colorless oil; H NMR δ 7.20-
1
1
,1-Dip h en yl-2-bu ta n ol (3a ): colorless oil; 1H NMR δ
7
.15-7.38 (10 H, m), 4.24 (1 H, dt, J ) 8.3, 3.5 Hz), 3.87 (1 H,
7.31 (5 H, m), 2.75 (2 H, s), 2.17 (1 H, s), 1.26-1.60 (10 H, m);
1
3
d, J ) 8.2 Hz), 1.64 (1 H, s), 1.35-1.60 (2 H, m), 0.96 (3 H, t,
C NMR: δ 137.2, 130.6, 128.1, 126.4, 71.1, 48.7, 37.3, 25.8,
1
3
+
J ) 7.4 Hz); C NMR δ 142.5, 141.5, 128.8, 128.7, 128.3, 128.2,
22.1; MS m/ z 190 (M , 0.2), 172 (5), 99 (100), 81 (75).
1-Allylcycloh exa n ol (11):23 colorless oil; H NMR δ 5.81-
5.95 (1 H, m), 5.06-5.16 (2 H, m), 2.20 (2 H, d, J ) 7.5 Hz),
1
1
26.7, 126.4, 75.0, 58.3, 27.8, 10.0.
N-(Dip h en ylm eth yl)a n ilin e (4):18 1H NMR δ 7.20-7.36
1.38-1.65 (10 H, m), 1.24-1.34 (1 H, m); 13C NMR δ 133.7,
(
10 H, m), 7.09 (2 H, t, J ) 8.0 Hz), 6.67 (1 H, t, J ) 7.3 Hz),
3
+
6
1
1
.52 (2 H, d, J ) 7.6 Hz), 4.19 (1H, s); 1 C NMR: δ 147.3, 142.8,
118.6, 70.9, 46.7, 37.4, 25.8, 22.2; MS m/ z 122 (M - H
2
O),
+
29.1, 128.7, 127.4, 127.3, 117.6, 113.4; MS m/z 259 (M , 18),
99 (100), 81(90).
82 (7), 167 (100).
-(Dip h en ylm eth yl)cycloh exa n ol (3b): colorless oil; H
Syn th esis of 9a ,b a n d 13a ,b via Lith ia tion a n d Red u c-
tive Cou p lin g: Gen er a l P r oced u r e. N-Benzylbenzotriazole
(6) or N-allylbenzotriazole (10) (5 mmol) was dissolved in THF
(25 mL) and cooled to -78 °C under argon. BuLi (5.5 mmol,
1.6 M in hexanes) was introduced via a syringe. The resulting
deep blue solution was treated with butyl bromide (5 mmol,
for 9a ,b and 13a ) or iodomethane (5 mmol, for 13b), and the
reaction temperature was allowed to warm to rt over 3 h
(solution A, light yellow). In another reaction flask (B), 25
mmol of lithium (0.57 g, 30% dispersion in mineral oil) was
washed twice with THF (2 × 20 mL) under argon. Fifteen
mL of THF was added, and the suspension was cooled to -78
°C. The solution A was transferred to a dropping funnel
1
1
NMR δ 7.54 (4 H, d, J ) 7.1 Hz), 7.25-7.31 (4 H, m), 7.16-
7
.22 (2 H, m), 3.86 (1 H, s), 1.39-1.60 (9 H, m), 1.26-1.32 (2
1
3
H, m); C NMR δ 141.5, 129.8, 128.2, 126.3, 73.5, 61.7, 37.2,
+
2
5.6, 22.1; MS m/z 266 (M , 0.2), 248 (4), 168 (100). Anal.
Calcd for C19 22O: C, 85.67; H, 8.32. Found: C, 85.30; H, 8.70.
,1-Dip h en yl-2-d eca n ol (3c): colorless oil; H NMR δ
H
1
1
7
4
1
1
3
.37-7.39 (2 H, m), 7.23-7.33 (6 H, m), 7.16-7.21 (2 H, m),
.30-4.36 (1 H, m), 3.88 (1 H, d, J ) 8.3 Hz), 1.64 (1 H, s),
.24-1.52 (14 H, m), 0.88 (3 H, t, J ) 6.6 Hz); 13C NMR δ
42.6, 141.5, 128.8, 128.7, 128.5, 128.2, 126.7, 126.4, 73.7, 58.7,
5.0, 31.8, 29.5, 29.2, 25.8, 22.6, 14.1. Anal. Calcd for
20
C H30O: C, 85.11; H, 9.74. Found: C, 84.80; H, 10.25.
1
9
1
,2,2-Tr ip h en yleth a n ol (3d ): white solid; mp 87-89 °C
9 1
(
20) Brook, A. G.; Warner, C. M.; McGriskin, M. E. J . Am. Chem.
Soc. 1959, 81, 981.
21) Gelin, R.; Chantegrel, B. Bull. Soc. Chim. Fr. 1971, 13, 2527.
(22) Huang, Y.-Z.; Liao, Y.; Chen, C. J . Chem. Soc., Chem. Commun.
1990, 85.
(23) Katzenellenbogen, J . A.; Lenox, R. S. J . Org. Chem. 1973, 38,
326.
1
(
lit. 86-88 °C); H NMR δ 7.39 (2 H, d, J ) 7.1 Hz), 7.32 (2
(
(
17) Azzena, U.; Melloni, G.; Fenude, E.; Fin a` , C.; Marchetti, M.;
Sechi, B. Synth. Commun. 1994, 24, 591.
(
(
18) Wittig, G.; Hesse, A. Liebigs Ann. Chem. 1971, 746, 174.
19) Kropf, H.; Angi, F. J . Chem. Res., Synop. 1982, 136.

4
120 J . Org. Chem., Vol. 62, No. 12, 1997
Katritzky and Qi
connected to flask B and mixed with 3-pentanone (6 mmol,
for 9a and 13a ), methyl benzoate (6 mmol, for 9b), or
cyclohexanone (6 mmol, for 13b). The mixed solution was
dropped into the lithium suspension over 1 h and kept another
hour before being quenched by water (15 mL), at the same
temperature. The reaction mixture was separated, and the
aqueous phase was extracted with ether (2 × 20 mL). The
combined organic solution was washed with saturated NaCl
solution, dried, and evaporated to give the crude product,
which was purified by flash column chromatography (eluent:
Syn th esis of 3,5-Dieth yl-4-p h en yl-3,5-h ep ta n ed iol via
Dou ble Red u ctive Cou p lin gs. Lithium (0.57 g, 25 mmol,
30% dispersion in mineral oil) was washed twice with THF (2
× 20 mL) under argon. THF (10 mL) was added, and the
suspension was treated with 1,2-dibromoethane (2.5 mmol)
and then cooled to -78 °C. The solution of R,R-bis(benzotria-
zolyl)toluene (2.5 mmol) and 3-pentanone (6 mmol) in THF
(30 mL) was dropped into the lithium suspension over 1 h and
kept another hour before being quenched by water (15 mL),
at the same temperature. The reaction mixture was sepa-
rated, and the aqueous phase was extracted with ether (2 ×
20 mL). The combined organic solution was washed with
saturated NaCl solution, dried, and evaporated to give the
crude product, which was purified by flash column chroma-
tography (eluent: hexanes-ethyl acetate) to afford the pure
product 19 (60%) and byproduct 3-benzyl-3-pentanol (20, 20%).
hexanes-ethyl acetate) to afford the pure product.
1
3
-Eth yl-4-p h en yl-3-octa n ol (9a ): colorless oil; H NMR
δ 7.20-7.35 (5H, m), 2.67 (1H, dd, J ) 10.6, 4.8 Hz), 1.70-
1
1
1
7
2
.86 (2H, m), 1.60 (2H, q, J ) 7.0 Hz), 1.20-1.42 (4H, m), 0.98-
.16 (3H, m), 0.80-0.96 (9H, m); 13C NMR: δ 141.6, 129.8,
28.0, 126.2, 76.2, 52.1, 30.4, 29.2, 28.4, 28.0, 22.8, 14.0, 8.0,
.6; HRMS (CI) calcd for C16
35.2059.
H
26O + H 235.2062, found
3
,5-Dieth yl-4-p h en yl-3,5-h ep ta n ed iol (19): white solid;
1
mp 110-112 °C; H NMR δ 7.74 (1H, d, J ) 7.0 Hz), 6.95-
P h en yl 1-p h en ylp en tyl k eton e (9b):24 colorless oil; H
1
7
1
.36 (4H, m), 3.34 (2H, s), 2.96 (1H, s), 1.74-1.90 (4H, m),
.40-1.52 (2H, m), 1.08-1.20 (2H, m), 0.92 (6H, t, J ) 7.2
NMR δ 7.97 (2H, d, J ) 7.2 Hz), 7.20-7.49 (8H, m), 4.54 (1H,
t, J ) 7.3 Hz), 2.14-2.26 (1H, m), 1.78-1.90 (1H, m), 1.16 -
13
Hz), 0.70 (6H, t, J ) 7.2 Hz); C NMR δ 140.6, 132.0, 130.1,
1
3
1
1
2
.40 (4H, m), 0.87 (3H, t, J ) 6.9 Hz); C NMR δ 200.1, 132.7,
1
27.4, 126.1, 79.6, 55.1, 31.2, 31.0, 8.4, 7.6. Anal. Calcd for
29.6, 128.8, 128.6, 128.5, 128.2, 126.9, 126.4, 53.7, 33.8, 29.9,
2.7, 13.9; MS m/ z 252 (M , 1), 196 (8), 105 (100).
-Eth yl-4-eth en yl-3-octa n ol (13a ): colorless oil; H NMR
C
17
H
28
O
2
: C, 77.22; H, 10.67. Found: C, 77.49; H, 11.06.
+
-Ben zyl-3-p en ta n ol (20):25 colorless oil; H NMR δ 7.12-
1
3
1
3
7
.36 (5H, m), 2.75 (2H, s), 1.44 (4H, q, J ) 7.0 Hz), 1.30 (1H,
δ 5.65 (1H, dt, J ) 17.1, 9.9 Hz), 5.15 (1H, dd, J ) 10.2, 2.5
Hz), 5.06 (1H, dd, J ) 17.1, 2.4 Hz), 2.09 (1H, dt, J ) 10.2, 2.5
Hz), 1.44-1.60 (5H, m), 1.10-1.38 (6H, m), 1.84-1.92 (9H,
13
br s), 0.96 (6H, t, J ) 7.0 Hz); C NMR: δ 137.5, 130.5, 128.1,
1
26.3, 74.5, 44.7, 30.4, 8.0.
1
3
m); C NMR δ 139.2, 117.6, 75.2, 51.5, 30.3, 28.6, 28.4, 27.8,
2.7, 14.0, 7.5, 7.4; HRMS (CI) calcd for C12 24O + H 185.1905,
found 185.1907.
-(1-Meth yla llyl)-1-cycloh exa n ol (13b):23 colorless oil; H
Su p p or tin g In for m a tion Ava ila ble: H and 13C NMR and
1
2
H
HRMS spectra for products 3c, 9a , and 13a (11 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.
1
1
NMR δ 5.77-5.89 (1H, m), 5.03-5.09 (2H, m), 2.15-2.20 (1H,
m), 1.39-1.66 (10H, m), 1.29 (1H, s), 1.20 (3H, d, J ) 7.0 Hz);
1
3
C NMR δ 140.4, 115.8, 72.4, 48.3, 35.0, 34.4, 25.9, 21.8, 14.1;
+
2
MS m/ z 136 (M - H O, 1.5), 99 (100).
J O962246L
(
24) Mukaiyama, T.; Kamio, K.; Takei, H. Bull. Chem. Soc. J pn.
1
972, 45, 3723.
(25) Kropf, H.; Bernert, C.-R. Liebigs Ann. Chem. 1971, 751, 109.