Novel and Facile Syntheses of Alkenyl, Alkynyl, and Aryl 1,2-Diketones

Article abstract of DOI:10.1021/jo970092j

Novel and facile routes to alkenyl, alkynyl, and aryl 1,2-diketones utilize treatment of benzotriazole derivatives 1, 7a,b, and 15a-d with butyllithium and subsequent reaction with esters or acid chlorides to yield the substituted intermediates 2a-d, 8a,b, and 16a-g, Reactions of the deprotonated 1 and 7 with α,β-unsaturated aldehydes followed by oxidation also produces similar intermediates 5 and 11a,b. Subsequent hydrolyses of the intermediates of type 2, 5, 8,11, and 16 afford diverse 1,2-diketones in good yields.

Full text of DOI:10.1021/jo970092j

J . Org. Chem. 1997, 62, 4125-4130
4125
Novel a n d F a cile Syn th eses of Alk en yl, Alk yn yl, a n d Ar yl
1,2-Dik eton es
Alan R. Katritzky,* Zuoquan Wang, Hengyuan Lang, and Daming Feng
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received J anuary 17, 1997X
Novel and facile routes to alkenyl, alkynyl, and aryl 1,2-diketones utilize treatment of benzotriazole
derivatives 1, 7a ,b, and 15a -d with butyllithium and subsequent reaction with esters or acid
chlorides to yield the substituted intermediates 2a -d , 8a ,b, and 16a -g. Reactions of the
deprotonated 1 and 7 with R,â-unsaturated aldehydes followed by oxidation also produces similar
intermediates 5 and 11a ,b. Subsequent hydrolyses of the intermediates of type 2, 5, 8, 11, and 16
afford diverse 1,2-diketones in good yields.
In tr od u ction
prepared by reaction of the metal (Cd, Zn) acetylide with
acyl chloride.6 Leyendecker et al.7 synthesized alkynyl
1,2-diketones in unspecified overall yields by a four-step
conversion of R-amino acids via intermediate 2-(trifluo-
romethyl)-3-oxazolin-5-ones.
1,2-Diketones have found widespread applications in
the synthesis of various heterocyclic compounds.1 The
synthesis of simple alkyl- and aryl-substituted 1,2-
diketones has been extensively investigated, and many
good methods are available through (i) oxidations,2 (ii)
use of masked acyl anion synthons,3a-f and (iii) other
approaches.4
By contrast, relatively few examples are documented
of the preparation of alkenyl- and alkynyl-substituted 1,2-
diketones. Ahmad and Iqbal5 reported the preparation
of methyl alkenyl 1,2-diketones by cobalt(II) chloride
catalyzed coupling of acetic anhydride with the corre-
sponding R,â-unsaturated aldehydes. 1-Phenyl-1-pen-
tyne-3,4-dione (an acetylenic 1,2-diketone) was previously
We have recently reported convenient benzotriazole
acyl anion methodologies for the synthesis of a wide
variety of simple and functionalized alkenyl,8 alkynyl,9
aryl/heteroaryl,10 and alkyl11 ketones and of alkenoyl-,
alkynoyl-, aroyl-, and heteroaroylsilanes.12 The benzo-
triazole-stabilized carbanions utilized share the following
features: (i) ready availability of starting materials; (ii)
adequate reactivity toward a diverse range of electro-
philes including alkyl halides, aldehydes, ketones, and
imines; and (iii) easy hydrolysis of the alkylated inter-
mediates. Reactions with electrophiles are also regiospe-
cific. We have reported the preparation of an acetylenic
R-diketone (PhCtCCOCOMe) by reaction of lithiated
1-(benzotriazol-1-yl)-3-phenylpropargyl ethyl ether with
ethyl acetate followed by mild hydrolysis.9 Faust and
Weber13 have recently utilized our methodology to syn-
thesize 1-phenyl-1,5-hexadiyne-3,4-diones (PhCtCCOCOC
tCR) which could not be prepared by conventional
methods. We now report the successful extension of our
benzotriazole acyl synthon methodology to reactions with
acid chlorides, esters, or aldehydes followed by oxidation
and demonstrate that these strategies provide facile and
general routes to diverse alkenyl, alkynyl, and aryl 1,2-
diketones.
X Abstract published in Advance ACS Abstracts, May 15, 1997.
(1) For some recent examples, see the following. (a) 1,2,4-triazines:
Taylor, E. C.; Macor, J . E.; French, L. G. J . Org. Chem. 1991, 56, 1807.
(b) Bridged quinoxalines: Christl, M.; Kraft, A. Angew. Chem., Int.
Ed. Engl. 1988, 27, 1369. (c) Chiral piperazines: Nantz, M. H.; Lee,
D. A.; Bender, D. M.; Roohi, A. H. J . Org. Chem. 1992, 57, 6653. (d)
Imidazoles: Khalaj, A.; Ghafari, M. Tetrahedron Lett. 1986, 27, 5019.
(e) Quinolizinium cation: Ezquerra, J .; Alvarez-Builla, J . J . Heterocycl.
Chem. 1986, 23, 1151. (f) Isoquinolones: Kiselyov, A. S. Tetrahedron
Lett. 1995, 36, 493. (g) Enediol iminocarbonates: Guirado, A.; Zapata,
A.; Galvez, J . Tetrahedron Lett. 1994, 35, 2365.
(2) See the following for recent examples of oxidations. (a) Acyl-
oins: Fukumoto, T.; Matsuki, T.; Hu, N. X.; Aso, Y.; Otsubo, T.; Ogura,
F. Chem. Lett. 1990, 2269. (b) Benzoins: Levi, E. M.; Hauser, C. R. J .
Org. Chem. 1969, 34, 2482. (c) Benzyl ketones: Bonadies, F.; Bonini,
C. Synth. Commun. 1988, 18, 1573. (d) Monoketones: Rao, D. V.;
Stuber, F. A.; Ulrich, H. J . Org. Chem. 1979, 44, 456. (e) Alkynes:
Ballistreri, F. P.; Failla, S.; Tomaselli, G. A.; Curci, R. Tetrahedron
Lett. 1986, 27, 5139. Zibuck, R.; Seebach, D. Helv. Chim. Acta 1988,
71, 237. (f) Acyl phosphorus ylides: Bestmann H. J .; Kumar, K.;
Kisielowski, L. Chem. Ber. 1983, 116, 2378. (g) R-Alkylthio ketones:
Carre, M. C.; Caubere, P. Tetrahedron Lett. 1985, 26, 3103. (h) Vicinal
diols: Regen, S. L.; Whitesides, G. M. J . Org. Chem. 1972, 37, 1832.
(3) (a) Page, P. C. B.; Graham, A. E.; Park, B. K. Tetrahedron 1992,
48, 7265 and references therein. (b) Martre, A.-M.; Mousset, G.; Rhlid,
R. B.; Veschambre, H. Tetrahedron Lett. 1990, 31, 2599. (c) Seebach,
D.; Corey, E. J . J . Org. Chem. 1975, 40, 231. (d) Marshall, J . A.; Seitz,
D. E. J . Org. Chem. 1974, 39, 1814. (e) Fuji, K.; Ueda, M.; Fujita, E.
J . Chem Soc., Chem. Commun. 1983, 49. (f) Olah, G. A.; Wu, A.-h. J .
Org. Chem. 1991, 56, 902. (g) J ousseaume, B.; Vilcot, N.; Ricci, A.;
Tiekink, E. R. T. J . Chem Soc., Perkin Trans. 1 1994, 2283.
Resu lts a n d Discu ssion
Benzotriazole R,â-unsaturated acyl anion synthon 1
was prepared by reaction of the corresponding acetal with
(6) Yashina, O. G.; Vereshchagin, L. I. Zh. Org. Khim. 1968, 4, 2104;
Chem. Abstr. 1969, 70, 67812e.
(7) Leyendecker, J .; Niewˆıhner, U.; Steglich, W. Tetrahedron Lett.
1983, 24, 2375.
(8) (a) Katritzky, A. R.; J iang, J . J . Org. Chem. 1995, 60, 6. (b)
Katritzky, A. R.; Zhang, G.; J iang, J . J . Org. Chem. 1995, 60, 7589. (c)
Katritzky, A. R.; J iang, J . J . Org. Chem. 1995, 60, 7597. (d) Katritzky,
A. R.; Zhang, G.; J iang, J . J . Org. Chem. 1995, 60, 7605. (e) Katritzky,
A. R.; Feng, D.; Lang, H. J . Org. Chem. 1997, 62, 706.
(9) Katritzky, A. R.; Lang, H. J . Org. Chem. 1995, 60, 7612.
(10) Katritzky, A. R.; Lang, H.; Wang, Z.; Zhang, Z.; Song, H. J .
Org. Chem. 1995, 60, 7619.
(11) Katritzky, A. R.; Lang, H.; Wang, Z.; Zhu, L. J . Org. Chem.
1996, 61, 7551.
(12) Katritzky, A. R.; Wang, Z.; Lang, H. Organometallics 1996, 15,
486.
(13) Faust, R.; Weber, C. Liebigs Ann. 1996, 1235.
(14) Poos, G. I.; Arth, G. E.; Beyler, R. E. and Sarett, L. H. J . Am.
Chem. Soc. 1953, 75, 422.
(4) (a) Mohr, B.; Enkelmann, V.; Wegner, G. J . Org. Chem. 1994,
59, 635. (b) Souppe, J .; Namy, J .-L.; Kagan, H. B. Tetrahedron Lett.
1984, 25, 2869. (c) Murakami, M.; Masuda, H.; Kawano, T.; Nakamura,
H.; Ito, Y. J . Org. Chem. 1991, 26, 1. (d) Sibi, M. P.; Sharma, R.;
Paulson, K. L. Tetrahedron Lett. 1992, 33, 1941. (e) Verlhac, J .-B.;
Chanson, E.; J ousseaume, B.; Quintard, J .-P. Tetrahedron Lett. 1985,
26, 6075. (f) Devasagayaraj, A.; Periasamy, M. Tetrahedron Lett. 1992,
33, 1227. (g) Seyferth, D.; Weinstein, R. M.; Hui, R. C.; Wang, W.-L.;
Arther, C. M. J . Org. Chem. 1991, 56, 5768. (h) Sosnovskii, G. M.;
Astapovich, I. V. J . Org. Chem. USSR (Engl. Trans.) 1993, 29, 71. (i)
Nudelman, N. S.; Outumura, P. J . Org. Chem. 1982, 47, 4347.
(5) Ahmad, S.; Iqbal, J . J . Chem Soc., Chem. Commun. 1987, 692.
S0022-3263(97)00092-3 CCC: $14.00 © 1997 American Chemical Society

4126 J . Org. Chem., Vol. 62, No. 12, 1997
Katritzky et al.
Sch em e 1
Sch em e 2
Sch em e 3
benzotriazole, as previously reported.8e Treatment of 1
with BuLi and reaction with an ester followed by hy-
drolysis gave R-alkenyl-substituted 1,2-diketones 4a -d
in moderate overall yields (Scheme 1). Thus, treatment
of 1 with BuLi at -78 °C in an oxygen free atmosphere
for 5 min gave a deep blue-green solution, which was then
reacted at -78 °C with methyl benzoate for 5 min.
Subsequent quenching with water-HCl was followed by
allowing the reaction mixture to warm to room temper-
ature with stirring over 4 h. Final workup afforded 4a
in 41% yield. Compounds 4b-d were similarly prepared
in 54-61% yields. The use of an ester and not an acid
chloride as the electrophile is critical to avoid a lower
yield. The present results indicate that the reaction
tolerates both alkyl- and aryl-substituted esters and
allows the preparation of both alkyl alkenyl 1,2-diketones
(4b-d ) and aryl alkenyl 1,2-diketone (4a ).
Our previous work has shown that use of R,â-unsatur-
ated esters as electrophiles in the reactions with acyl
anion synthon 1 leads regiospecifically to 1,4-addition
products which eventually produce 1,4-dicarbonyl com-
pounds after hydrolysis.8e We have now found an alter-
native procedure which readily provides the desired 1,2-
diketone 6 in a reasonable yield. Thus, treatment of 1
with BuLi followed by reaction with cinnamaldehyde
gave the crude intermediate 3, which underwent oxida-
tion to produce the benzotriazole derivative 5 in 47%
overall yield based on 1. Subsequent hydrolysis afforded
the alkenyl-substituted 1,2-diketone 6 in 82% yield.
The method we previously used9 to prepare the acety-
lenic R-diketone, 1-phenyl-1-pentyne-3,4-dione, by reac-
tion of ethynyl-substituted acyl anion equivalent 7 with
ethyl acetate has now been extended satisfactorily to
other alkyl- and aryl-substituted esters. Treatment of
7a with BuLi followed by reaction with methyl benzoate
gave the intermediate 8a in 63% yield (Scheme 2).
Subsequent hydrolysis afforded the expected acetylenic
1,2-diketone 9a in 84% yield. Compound 9b was simi-
larly prepared in 69% yield without isolation and char-
acterization of the intermediate 8b.
Attempted preparation of acetylenic 1,2-diketones of
type 12 by using R,â-unsaturated esters and R,â-unsatur-
ated acid chlorides as electrophiles in the reactions with
synthon 7 failed: such reactions produced complicated
mixtures as indicated by TLC and NMR spectra. How-
ever, a procedure similar to that applied above to the
preparation of alkenyl-substituted 1,2-diketone 6 was
successful in producing 1,2-diketones of type 12. Thus,
treatment of 7a with 1 equiv of BuLi followed by
quenching with R-methyl-trans-cinnamaldehyde gave
intermdiate 10a in 51% yield (Scheme 3). Subsequent
application of Sarett’s modification of J ones oxidation14
yielded the benzotriazole derivative 11a in 93% yield.
Finally, hydrolysis with H2SO4-H2O-acetone at 0-25
°C produced the expected 1,2-diketone 12a in 83% yield.
Compound 12b was prepared by a similar sequence. The
hydrolysis conditions have to be controlled carefully,
otherwise side reaction can occur. We have found that
hydrolysis of the intermediate 11a with HCl-H2O-
acetone at 0-22 °C resulted in the formation of 37%
diketone 13 along with the expected 12a . It is believed
that HCl partially added to the triple bond of the formed
1,2-diketone 12a . Compounds of type 12 were previously
unknown.
The versatility of this benzotriazole-assisted diketone
synthesis has been further demonstrated by the conve-
nient syntheses of aryl 1,2-diketones 17a -g. 1-(Phe-
noxymethyl)benzotriazole (14) and its alkylated deriva-
tive (15a ) were prepared according to our previously
described procedure.11 Treatment of compound 15d with
butyllithium at -78 °C for 5 min followed by addition of
benzoyl chloride gave intermediate 16f in 84% isolated
yield. Further heating of 16f in a mixture of AcOH-H2-
SO4-H2O under reflux for 13.5 h afforded the desired
1,2-diketone 17f in 92% yield. The structures of 16f and
17f were fully characterized by NMR spectroscopy and
elemental analysis. Intermediate 16b and diketone 17b

Synthesis of Alkenyl, Alkynyl, and Aryl 1,2-Diketones
J . Org. Chem., Vol. 62, No. 12, 1997 4127
reported in the literature. The 13C NMR spectra showed
the two characteristic carbonyl carbon signals in the
range of 176-208 ppm.
Sch em e 4
In conclusion, novel and convenient routes to alkyl-,
alkenyl-, alkynyl-, and aryl-substituted 1,2-diketones in
good yields were developed from readily available start-
ing materials, by utilizing simple methodology.
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 in CDCl3 with TMS
or CDCl3, respectively, as the internal reference. 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.
were similarly prepared in 86% and 83% yields, respec-
tively. Compounds 17a ,c,e,g were obtained in 52-72%
overall yields directly from 15 without purification of the
intermediates 16a ,c,e,g.
Gen er a l P r oced u r e for th e P r ep a r a tion of 4a -d . To
a solution of 1-(benzotriazol-1-yl)-1-ethoxy-2-hexene (1, 1.23
g, 5 mmol) in THF (50 mL) at -78 °C was added n-
butyllithium (1.6 M in cyclohexane, 3.2 mL, 5.1 mmol). The
solution was stirred at this temperature for 5 min and the
appropriate electrophile (methyl benzoate, butyl acetate, ethyl
octanoate, or methyl decanoate; 5 mmol) added. After the
solution was stirred at -78 °C for an additional 5 to 10 min,
it was quenched at this temperature with water (50 mL). A
solution of hydrochloric acid (1 mL, 37%) in water (5 mL) was
added at this temperature, and the mixture was stirred at
room temperature for 4 h. The resulting solution was ex-
tracted with diethyl ether (2 × 50 mL) and washed with
aqueous sodium hydroxide solution (0.5 N, 2 × 50 mL). The
organic phase was separated and dried over anhydrous MgSO4.
Evaporation of the solvent gave a residue which was purified
by column chromatography (hexane/ethyl acetate, 30:1).
tr a n s-1-P h en yl-4-h ep ten e-1,2-d ion e (4a ): obtained as a
yellow oil, yield 41%; 1H NMR δ 0.95 (t, 3 H, J ) 7.4 Hz), 1.53
(sextet, 2 H, J ) 7.3 Hz), 2.30 (q, 2 H, J ) 7.2 Hz), 6.47 (dt, 1
H, J ) 16.2, 1.5 Hz), 7.01 (dt, 1 H, J ) 16.2, 6.9 Hz), 7.50 (t,
2 H, J ) 7.0 Hz), 7.64 (t, 1 H, J ) 7.4 Hz), 7.96 (d, 2 H, J )
8.6 Hz); 13C NMR δ 13.6, 20.9, 35.1, 127.1, 128.8, 129.9, 132.8,
134.5, 155.4, 193.5, 193.6; HRMS (CI) calcd for C13H15O2 (M+
+ 1) 203.1072, found 203.1106.
These sequences of type 15 f 17 were thus very
effective, provided aroyl chlorides or aliphatic acid chlo-
rides without an active R-proton were used as the
electrophile indicated in Scheme 4. However, the at-
tempted use of esters or of aliphatic acid chlorides
containing R-hydrogen as electrophiles led to low yields
or complicated mixtures. For the esters this may be due
to the relatively low stability of the anion formed from
15 in the reaction with less reactive esters (compared
with acid chlorides); by contrast, in the case of the
synthesis of 4 and 9, the benzotriazole-stabilized anions
which are formed from the deprotonation of 1 and 7 are
further stabilized by alkenyl and alkynyl groups. For
normal aliphatic acid chlorides, failure to obtain the
expected intermediates could be attributed to the kineti-
cally controlled equilibrium leading to the deprotonation
of the electrophiles at the R-position.
Hydrolysis of the intermediates 16 derived from other
electrophiles (RX, RCHO, RCOR, etc.) was previously
carried out in refluxing ethanol containing a small
amount of H2SO4 for only 10-20 min.11 The present
relatively difficult hydrolysis of 16 derived from acid
chlorides can be mainly attributed to the electron-
withdrawing effect of the carbonyl group. However,
compared with the commonly used acyl anion equivalent,
1,3-dithiane, which requires either the use of mercury
salts (and still gave low yields)15 or of the electrochemical
anodic oxidation3b to deprotect the dithio groups in the
preparation of 1,2-diketones (other available methods for
deprotection of 1,3-dithiane3c,16 did not mention the syn-
thesis of 1,2-diketones), the present method, with readily
available starting materials and a simple procedure,
represents an optimal synthesis of 1,2-diketones of type
17. Although a variety of approaches to the synthesis of
1,2-diketones have been developed,17 most involve oxalic
acid derivatives, and this often causes problems in
obtaining unsymmetrical 1,2-diketones.18 The present
method can be used to obtain both symmetrically and
unsymmetrically functionalized 1,2-diketones.
tr a n s-4-Octen e-2,3-d ion e (4b): obtained as a yellow oil,
yield 54%; 1H NMR δ 0.96 (t, 3 H, J ) 7.3 Hz), 1.54 (sextet, 2
H, J ) 7.3 Hz), 2.29 (q, 2 H, J ) 7.2 Hz), 2.39 (s, 2 H), 6.74
(dt, 1 H, J ) 15.9, 1.4 Hz), 7.11-7.22 (m, 1 H); 13C NMR δ
13.6, 21.1, 24.4, 35.2, 122.6, 154.0, 187.1, 199.2. Anal. Calcd
for C8H12O2: C, 68.55; H, 8.63. Found: C, 68.71; H 8.70.
tr a n s-4-Tetr a d ecen e-6,7-d ion e (4c): obtained as a yellow
1
oil, yield 61%; H NMR δ 0.80 -1.00 (m, 6 H), 1.20-1.40 (m,
8 H), 1.44-1.65 (m, 4 H), 2.28 (q, 2 H, J ) 7.2 Hz), 2.78 (t, 2
H, J ) 7.4 Hz), 6.69 (d, 1 H, J ) 15.9 Hz), 7.14 (dt, 1 H, J )
15.9, 6.8 Hz); 13C NMR δ 13.6, 13.9, 21.1, 22.5, 23.0, 28.9, 29.0,
31.6, 35.1, 36.8, 123.2, 153.7, 188.0, 201.7; HRMS (CI) calcd
for C14H25O2 (M+ + 1) 225.1855, found 225.1854.
tr a n s-4-Hexa d ecen e-6,7-d ion e (4d ): obtained as a yellow
1
oil, yield 60%; H NMR δ 0.90 (t, 3 H, J ) 6.6 Hz), 0.97 (t, 3
H, J ) 7.4 Hz), 1.22-1.40 (m, 12 H), 1.50-1.68 (m, 4 H), 2.25-
2.32 (m, 2 H), 2.80 (t, 2 H, J ) 7.4 Hz), 6.71 (dt, 1 H, J ) 15.9,
1.7 Hz), 7.15 (dt, 1 H, J ) 15.9, 6.9 Hz); 13C NMR δ 13.6, 14.0,
21.1, 22.6, 23.0, 29.1, 29.2, 29.3, 29.4, 31.8, 35.1, 36.9, 123.2,
153.7, 188.1, 201.7; HRMS (CI) calcd for C16H29O2 (M+ + 1)
253.2168, found 253.2165.
The structures for all new compounds are supported
by 1H and 13C NMR spectroscopy and microanalyses. The
data for known compounds are consistent with data
1-P h en yl-4-(ben zotr ia zol-1-yl)-4-eth oxy-(E,E)-1,5-n on a -
d ien -3-on e (5). To a solution of trans-1-(benzotriazol-1-yl)-
1-ethoxy-2-hexene (1, 2.73 g, 11.1 mmol) in THF (40 mL) at
-78 °C was added n-butyllithium (1.6 M in cyclohexane, 7.0
mL, 11.2 mmol) dropwise. The solution was stirred at this
temperature for 2 min and trans-cinnamaldehyde (1.52 g, 11.2
mmol) added. After the solution was stirred at -78 °C for 5
min, it was quenched at this temperature with water (30 mL)
and the mixture was extracted with ether (2 × 40 mL) and
dried over anhydrous MgSO4. Evaporation of the solvent and
purification of the residue by column chromatography (hexane/
(15) Corey, E. J .; Erickson, B. W. J . Org. Chem. 1971, 36, 3553.
(16) (a) Seebach, D.; Steinmu¨ller, D. Angew. Chem., Int. Ed. Engl.
1968, 7, 619. (b) Seebach, D.; Steinmu¨ller, D.; Demuth, F. Angew.
Chem., Int. Ed. Engl. 1968, 7, 620. (c) Gro¨bel, B.-T.; Seebach, D.
Synthesis 1977, 357. (d) Seebach, D.; Wilka, E.-M. Synthesis 1976, 476.
(17) Sibi, M. P.; Marvin, M.; Sharma, R. J . Org. Chem. 1995, 60,
5016.
(18) Faust, R. J . Prakt. Chem. 1997, 339, 98.

4128 J . Org. Chem., Vol. 62, No. 12, 1997
Katritzky et al.
ethyl acetate, 30:1) gave a mixture of two diastereoisomeric
alcohols with unreacted aldehyde (2.82 g), which was used for
the following reaction without further purification. To pyri-
dine (54 mL) at 15-20 °C was added CrO3 (5.4 g) in portions
with stirring. The temperature should be kept below 30 °C
during the addition. At the end of the addition a slurry of a
complex in pyridine remained. A solution of the above impure
alcohols in pyridine (54 mL) was combined with the slurry
prepared above, and the contents were mixed thoroughly for
8 h at room temperature. The reaction mixture was poured
into water and extracted with three portions of benzene-ether
(1:1) using filtration through Celite 545 to break the emulsions.
The combined organic solution was washed with water (30
mL), dried over anhydrous MgSO4, and finally concentrated
under high vacuum. The crude product was purified by
column chromatography (hexane/ethyl acetate, 30:1) to give
colorless prisms (1.96 g, 5.2 mmol), yield 47% and mp 108-
110 °C: 1H NMR δ 0.96 (t, 3 H, J ) 7.4 Hz), 1.13 (t, 3 H, J )
7.1 Hz), 1.50-1.62 (m, 2 H), 2.24-2.38 (m, 2 H), 2.89-2.96
(m, 1 H), 3.60-3.70 (m, 1 H), 6.25-6.40 (m, 1 H), 6.67 (d, 1 H,
J ) 15.9 Hz), 7.12 (d, 1 H, J ) 15.9 Hz), 7.35-7.50 (m, 5 H),
7.50-7.65 (m, 3 H), 7.84 (d, 1 H, J ) 15.6 Hz), 8.12 (d, 1 H, J
) 7.8 Hz); 13C NMR δ 13.6, 15.0, 21.9, 34.5, 59.8, 95.6, 111.9,
119.5, 120.1, 122.9, 124.3, 127.8, 128.7, 128.9, 131.0, 132.3,
solvent, the crude product was obtained as a yellow oil, which
was purified by column chromatography (hexane/ethyl acetate,
100:1) to give a yellow oil (0.37 g, 1.53 mmol), yield 84%: 1H
NMR δ 0.92 (t, 3 H, J ) 6.7 Hz), 1.25-1.55 (m, 6 H), 1.60-
1.75 (m, 2 H), 2.50 (t, 2 H, J ) 7.1 Hz), 7.54 (t, 2 H, J ) 7.7
Hz), 7.69 (t, 1 H, J ) 7.4 Hz), 8.05 (d, 2 H, J ) 8.0 Hz); 13C
NMR δ 13.8, 19.4, 22.3, 27.3, 28.4, 31.0, 79.6, 103.8, 128.7,
130.2, 131.5, 134.6, 178.8, 188.6. Anal. Calcd for C16H18O2:
C, 79.31; H, 7.49. Found: C, 79.26; H, 7.79.
1-P h en yl-1-d od ecyn e-3,4-d ion e (9b). To a solution of
1-(benzotriazol-1-yl)-3-phenylpropargyl ethyl ether (7b, 1.0 g,
3.60 mmol) in THF (30 mL) at -78 °C was added n-butyl-
lithium (1.6 M in cyclohexane, 2.25 mL, 3.6 mmol). The
solution was stirred at -78 °C for 2 min, during which time
the solution became dark blue. Ethyl nonanoate (0.68 g, 3.6
mmol) was added, and the solution was kept at -78 °C for an
additional 2-5 min. The reaction was quenched at -78 °C
with water (30 mL), extracted with diethyl ether (3 × 40 mL),
and dried over MgSO4. Evaporation of the solvent and
purification by column chromatogaphy (hexane/ethyl acetate,
30:1) gave a slightly green oil, which was dissolved in acetone
(15 mL) and cooled to 5 °C, and a cold hydrochloric acid
solution (concd HCl (3 mL) in acetone (15 mL)) was added.
The mixture was stirred at 5-20 °C for 15 min, and the
solution was extracted with ether (3 × 40 mL), washed with a
2 N Na2CO3 aqueous solution (3 × 50 mL), and dried over
MgSO4. Evaporation of the solvent gave a yellow oil (0.67 g,
2.48 mmol), yield 69%: 1H NMR δ 0.89 (t, 3 H, J ) 7.2 Hz),
1.20-1.40 (m, 10 H), 1.60-1.72 (m, 2 H), 2.84 (t, 2 H, J ) 7.2
Hz), 7.30-7.58 (m, 3 H), 7.68 (d, 2 H, 8.3 Hz); 13C NMR δ 14.0,
22.6, 23.0, 29.0, 29.2, 31.7, 36.2, 86.0, 99.1, 119.4, 128.7, 131.5,
134.3, 138.6, 146.0, 146.5, 189.8. Anal. Calcd for C23H25
-
N3O2: C, 73.58; H, 6.71; N, 11.19. Found: C, 73.41; H, 7.01;
N, 11.05.
1-P h en yl-(E,E)-1,5-n on a d ien e-3,4-d ion e (6). To a solu-
tion of 1-phenyl-4-(benzotriazol-1-yl)-4-ethoxy-(E,E)-1,5-nona-
dien-3-one (5, 0.46 g, 1.23 mmol) in acetone at 5 °C was added
a precooled H2SO4 aqueous solution (0.6 mL, 11%) in acetone
(10 mL), and the solution was stirred at 12-14 °C for 1.5 h.
Water (40 mL) was added to the solution, which was extracted
with diethyl ether (3 × 50 mL), and the combined organic
layers were washed with a 2 N Na2CO3 aqueous solution (3 ×
60 mL) and dried over anhydrous MgSO4. After filtration and
removal of the solvent the crude product was obtained as a
yellow oil, which was purified by column chromatography
(hexane/ethyl acetate, 250:1) to give a yellow oily product (0.23
g, 1 mmol), yield 82%: 1H NMR δ 0.97 (t, 3 H, J ) 7.4 Hz),
1.49-1.65 (m, 2 H), 2.25-2.60 (m, 2 H), 6.76 (d, 1H, J ) 15.9
Hz), 7.19 (dt, 1 H, J ) 15.9, 6.9 Hz), 7.35 (d, 1 H, J ) 16.4
Hz), 7.41-7.55 (m, 3 H), 7.60-7.70 (m, 2 H), 7.79 (d, 1 H, J )
16.4 Hz); 13C NMR δ 13.6, 21.0, 35.1, 120.0, 124.3, 128.8, 128.9,
131.2, 134.3, 147.5, 154.0, 189.5, 189.6. Anal. Calcd for
C15H16O2: C, 78.92; H, 7.06. Found: C, 78.81; H, 7.35.
1-P h e n yl-2-(b e n zot r ia zol-1-yl)-2-e t h oxy-3-d e cyn -1-
on e (8a ). To a solution of 1-(benzotriazol-1-yl)-3-hexylprop-
argyl ethyl ether (7a , 1 g, 3.5 mmol) in THF (40 mL) at -78
°C was added n-butyllithium (1.6 M in cyclohexane, 2.2 mL,
3.5 mmol) dropwise. The solution was stirred at -78 °C for 3
min, during which time the solution became dark blue. Methyl
benzoate was added, and the solution was kept at -78 °C for
an additional 35 min. After the reaction was quenched at -78
°C with water (40 mL), the mixture was extracted with ether
(2 × 40 mL) and dried over MgSO4. Evaporation of the solvent
and purification by column chromatography (hexane/ethyl
acetate, 30:1) gave colorless prisms (0.86 g, 2.2 mmol), yield
63% and mp 76-78 °C: 1H NMR δ 0.87 (t, 3 H, J ) 6.6 Hz),
1.15-1.45 (m, 9 H), 1.53-1.65 (m, 2 H), 2.44 (t, 2 H, J ) 7.0
Hz), 3.25-3.38 (m, 1 H), 4.15-4.28 (m, 1 H), 7.34-7.50 (m, 4
H), 7.52-7.68 (m, 2 H), 8.10 (d, 1 H, J ) 8.0 Hz), 8.22 (d, 2 H,
J ) 7.4 Hz); 13C NMR δ 13.8, 14.7, 19.0, 22.3, 27.6, 28.3, 31.1,
61.5, 72.3, 90.2, 97.6, 111.9, 120.0, 124.1, 127.7, 128.0, 130.7,
133.7, 176.2, 196.7; HRMS (FAB) calcd for C18
271.1698, found 271.1702.
H23O2 (M+ + 1)
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
10a ,b. To a solution of 1-(benzotriazol-1-yl)-3-propargyl ethyl
ether (7, 5.26 mmol) in THF (40 mL) at -78 °C was added
n-butyllithium (1.6 M in cyclohexane, 3.3 mL, 5.28 mmol)
dropwise. The solution was stirred at this temperature for 2
min, and the appropriate aldehyde (R-methyl-trans-cinnamal-
dehyde or trans-cinnamaldehyde, 5.26 mmol) was added and
the solution stirred at -78 °C for an additional 2-5 min. The
mixture was quenched at this temperature with water (20 mL),
extracted with diethyl ether (2 × 30 mL), and dried over
anhydrous MgSO4. Evaporation of the solvent and purification
of the residue by column chromatography (hexane/ethyl ac-
etate, 200:1) gave the corresponding product.
tr a n s-1-P h en yl-2-m eth yl-3-h yd r oxy-4-(ben zotr ia zol-1-
yl)-4-eth oxy-1-d od ecen -5-yn e (10a ). This compound was
obtained as two diastereoisomers of ca. equal amount and
overall yield is 51%. Isom er 1, less polar fraction: colorless
prisms, mp 123-125 °C;
1H NMR δ 0.87 (t, 3 H, J ) 6.5 Hz),
1.20-1.58 (m, 9 H), 1.59-1.71 (m, 2 H), 1.75 (s, 3 H), 2.45 (t,
2 H, J ) 7.1 Hz), 3.28 (br s, 1 H), 3.29-3.45 (m, 1 H), 4.00-
4.15 (m, 1 H), 4.80 (d, 1 H, J ) 3.3 Hz), 5.85 (s, 1 H), 6.85 (d,
2 H, J ) 7.2 Hz), 7.07-7.25 (m, 3 H), 7.34 (t, 1 H, J ) 7.5 Hz),
7.45 (t, 1 H, J ) 7.4 Hz), 7.96 (d, 1 H, J ) 8.1 Hz), 8.04 (d, 1
H, J ) 8.4 Hz);
13C NMR δ 13.8, 13.9, 14.6, 18.8, 22.3, 27.9,
28.5, 31.1, 61.4, 72.5, 82.2, 92.7, 93.9, 112.2, 119.9, 123.8, 126.3,
127.3, 127.6, 128.6, 129.9, 132.5, 133.4, 136.7, 146.3. Anal.
Calcd for C27
H33N3O2: C, 75.14; H, 7.71; N, 9.74. Found: C,
75.30; H, 7.88; N, 9.75. Isom er 2, more polar fraction: yellow
oil: 1H NMR δ 0.86 (t, 3 H, J ) 6.6 Hz), 1.15-1.50 (m, 9 H),
1.52-1.70 (m, 2 H), 1.85 (s, 3 H), 2.44 (t, 2 H, J ) 6.9 Hz),
3.21 (br s, 1 H), 3.22-3.41 (m, 1 H), 3.99-4.10 (m, 1 H), 4.86
(d, 1 H, J ) 4.8 Hz), 6.42 (s, 1 H), 7.09 (d, 2 H, J ) 7.2 Hz),
7.16-7.40 (m, 4 H), 7.43 (t, 1 H, J ) 7.4 Hz), 7.96 (d, 1 H, J )
132.2, 132.3, 133.5, 146.5, 186.9. Anal. Calcd for C24H27
-
N3O2: C, 74.01; H, 6.99; N, 10.79. Found: C, 74.02; H, 7.03;
N, 10.84.
8.4 Hz), 8.01 (d, 1 H, J ) 8.1 Hz);
13C NMR δ 13.8, 14.5, 15.6,
18.7, 22.2, 27.9, 28.4, 31.1, 61.5, 73.2, 81.5, 93.1, 93.2, 112.6,
119.5, 123.6, 126.2, 127.1, 127.7, 128.8, 129.4, 132.6, 134.4,
137.1, 146.1. Anal. Calcd for C27H33N3O2: C, 75.14; H, 7.71;
N, 9.74. Found: C, 75.31; H,7.99; N, 9.75.
tr a n s-1,6-Dip h en yl-3-h yd r oxy-4-(ben zotr ia zol-1-yl)-4-
eth oxy-1-h exen -5-yn e (10b). This compound was obtained
as a mixture of two diastereoisomers (ratio ) 1:1.5), the overall
yield is 52%; yellow plates, mp 62-65 °C: 1H NMR δ 1.10-
1.45 (m, 3 H), 3.30-3.55 (m, 1 H), 4.02-4.22 (m, 1 H), 5.12 (d,
1-P h en yl-3-Decyn e-1,2-dion e (9a). To a solution of 1-phen-
yl-2-(benzotriazol-1-yl)-2-ethoxy-3-decyn-1-one (8a , 0.71 g,
1.82 mmol) in acetone (37 mL) at 5 °C was added a precooled
H2SO4 aqueous solution (3 mL, 11%) in acetone (10 mL), and
the solution was stirred at room temperature for 19.5 h. Water
(40 mL) was added to the solution, which was extracted with
diethyl ether (3 × 40 mL), and the combined organic layers
were washed with a 2 N Na2CO3 aqueous solution (3 × 50 mL)
and dried over MgSO4. After filtration and removal of the

Synthesis of Alkenyl, Alkynyl, and Aryl 1,2-Diketones
J . Org. Chem., Vol. 62, No. 12, 1997 4129
0.4 H, J ) 6.3 Hz), 5.22 (d, 0.6 H, J ) 5.4 Hz), 6.15-6.25 (m,
0.4 H), 6.45-6.62 (m, 1 H), 6.86 (d, 0.6 H, J ) 15.9 Hz), 7.10-
7.75 (m, 13 H), 7.92-8.20 (m, 2 H); 13C NMR δ 14.7, 15.1, 61.9,
62.2, 77.3, 77.9, 81.1, 81.6, 91.3, 92.9, 93.2, 112.4, 112.5, 119.8,
119.9, 120.9, 124.0, 124.1, 124.3, 125.8, 126.5, 126.6, 127.5,
127.7, 127.8, 128.1, 128.2, 128.3, 128.4, 128.6, 129.5, 132.1,
132.6, 132.7, 133.4, 134.3, 136.2, 136.6, 146.2, 146.3. Anal.
Calcd for C26H23N3O2: C, 76.26; H, 5.66; N, 10.26. Found: C,
75.97; H, 5.78; N, 10.18.
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
11a ,b. To pyridine (30 mL) at 15-20 °C was added CrO3 (3
g) in portions with stirring. The temperature should be kept
below 30 °C during the addition. At the end of the addition a
slurry of a complex in pyridine remained. A solution of the
alcohol 10 (2.67 mmol) in pyridine (30 mL) was combined with
the slurry prepared above, and the contents were mixed
thoroughly for 50 h with the reaction of 10a , and 8 h with
10b, at room temperature. The reaction mixture was poured
into water and extracted with three portions of benzene/ether
(1:1) using filtration through Celite 545 to break the emulsions.
The combined organic solution was washed with water, dried
over anhydrous MgSO4, and finally concentrated under high
vacuum. Purification of the residue by column chromatogra-
phy (hexane/ethyl acetate, 30:1) gave the corresponding prod-
uct.
tr a n s-1-P h en yl-2-m eth yl-4-(ben zotr iazol-1-yl)-4-eth oxy-
1-d od ecen -5-yn -3-on e (11a ): yield 93%; yellow prisms, mp
68-70 °C; 1H NMR δ 0.83 (t, 3 H, J ) 6.3 Hz), 1.14-1.52 (m,
9 H), 1.53-1.72 (m, 2 H), 2.14 (s, 3 H), 2.47 (t, 3 H, J ) 6.9
Hz), 3.24-3.42 (m, 1 H), 4.11-4.30 (m, 1 H), 7.30-7.59 (m, 7
H), 7.64 (d, 1 H, J ) 8.4 Hz), 8.08 (d, 1 H, J ) 8.4 Hz), 8.14 (s,
1 H); 13C NMR δ 13.7, 14.2, 14.6, 18.9, 22.2, 27.6, 28.3, 30.9,
61.3, 72.5, 90.2, 96.6, 111.8, 119.8, 123.9, 127.5, 128.2, 128.7,
129.7, 131.6, 132.1, 135.3, 143.1, 146.4, 188.9. Anal. Calcd
for C27H31N3O2: C, 75.49; H, 7.27; N, 9.78. Found: C, 75.62;
H, 7.60; N, 9.72.
ature over 30 min. Water (40 mL) was added to the solution,
which was extracted with diethyl ether (3 × 40 mL), and the
combined organic layers were washed with a 2 N Na2CO3
aqueous solution (3 × 50 mL) and dried over MgSO4. After
filtration and removal of the solvent, the oily residue was
purified by column chromatography (hexane/ethyl acetate,
1000:1) to give the less polar fraction 12a (0.2 g, 0.71 mmol),
yield 37%, and more polar fraction 13 (0.23 g, 0.72 mmol) as
a yellow oil, yield 37%: 1H NMR δ 0.90 (t, 3 H, J ) 6.4 Hz),
1.20-1.48 (m, 6 H), 1.60-1.75 (m, 2 H), 2.19 (d, 3 H, J ) 1.0
Hz), 2.55 (t, 2 H, J ) 7.4 Hz), 6.55 (s, 1 H), 7.37-7.60 (m, 6
H); 13C NMR δ 12.6, 14.0, 22.4, 27.2, 28.3, 31.4, 41.6, 122.4,
128.6, 129.5, 130.2, 133.2, 135.1, 146.2, 154.1, 192.5, 196.0.
Anal. Calcd for C19H23O2Cl: C,71.67; H, 7.29. Found: C,
72.01; H, 7.61.
Gen er a l P r oced u r e for th e P r ep a r a tion of 15b -d . To
a solution of 1-(phenoxymethyl)benzotriazole (14, 17.8 mmol)
in THF (40 mL) at -78 °C was added n-butyllithium (1.6 M
in cyclohexane, 11.3 mL, 18.1 mmol). The solution was stirred
at this temperature for 5 min, and the appropriate electrophile
(1-iodohexane, 1-iododecane, or 1-bromo-3-phenylpropane, 11.8
mmol) was added. After the solution was stirred at -78 °C
for an additional 5 min, it was allowed to warm to room
temperature and quenched with water (20 mL). The mixture
was extracted with diethyl ether (2 × 50 mL), and the
combined organic layer was dried over anhydrous MgSO4.
Evaporation of the solvent gave a residue which was separated
by column chromatography (hexane/ethyl acetate, 30:1).
1-(Ben zotr ia zol-1-yl)-1-p h en oxyh ep ta n e (15b): obtained
as an oil; yield 86%; 1H NMR δ 0.87 (t, 3 H, J ) 6.8 Hz), 1.20-
1.90 (m, 8 H), 2.25-2.40 (m, 1 H), 2.42-2.60 (m, 1 H), 6.85(t,
1 H, J ) 6.8 Hz), 6.92-7.10 (m, 3 H), 7.19 (td, 2 H, J ) 7.0,
1.9 Hz), 7.36 (td, 1 H, J ) 8.2, 1.0 Hz), 7.47(td, 1 H, J ) 8.2,
1.0 Hz), 7.83 (d, 1 H, J ) 8.4 Hz), 8.05 (d, 1 H, J ) 8.4 Hz);
13C NMR δ 13.8, 22.3, 24.5, 28.4, 31.3, 34.6, 88.2, 111.0, 116.1,
119.9, 122.7, 124.1, 127.5, 129.5, 131.0, 146.6. 156.1. Anal.
Calcd for C19H23N3O: C, 73.76; H, 7.49; N, 13.58. Found: C,
73.87; H, 7.87; N, 13.91.
tr a n s-1,6-Dip h en yl-4-(b en zot r ia zol-1-yl)-4-et h oxy-1-
h exen -5-yn -3-on e (11b): yield 92%; yellow prisms, mp 122-
1
124 °C; H NMR δ 1.29 (t, 3 H, J ) 7.1 Hz), 3.35-3.50 (m, 1
1-(Ben zot r ia zol-1-yl)-1-p h en oxyu n d eca n e (15c): ob-
1
H), 4.14-4.28 (m, 1 H), 7.30-7.70 (m, 13 H), 7.73 (d, 1 H, J )
8.4 Hz), 7.91 (d, 1 H, J ) 15.9 Hz), 8.11 (d, 1 H, J ) 8.4 Hz);
13C NMR δ 14.6, 62.0, 79.8, 90.3, 93.0, 111.7, 118.7, 119.9,
120.4, 124.2, 127.8, 128.3, 128.6, 128.8, 129.7, 131.1, 131.9,
tained as an oil; yield 87%; H NMR δ 0.89 (t, 3 H, J ) 6.8
Hz), 1.15-1.65 (m, 16 H), 2.25-2.40 (m, 1 H), 2.42-2.60 (m,
1 H), 6.85 (t, 1 H, J ) 6.8 Hz), 6.91-7.00 (m, 3 H), 7.19 (t, 2
H, J ) 8.0 Hz), 7.34 (t, 1 H, J ) 7.2 Hz), 7.46 (t, 1 H, J ) 7.2
Hz), 7.83 (d, 1 H, J ) 8.1 Hz), 8.05 (d, 1 H, J ) 8.4 Hz); 13C
NMR δ 14.0, 22.6, 24.6, 28.8, 29.1, 29.2, 29.3, 29.4, 31.8, 34.7,
88.3, 111.1, 111.2, 116.1, 120.0, 122.8, 124.2, 127.6, 129.6,
131.1, 146.7, 156.1. Anal. Calcd for C23H31N3O: C, 75.58; H,
8.55; N, 11.50. Found: C, 75.76; H, 8.83; N, 11.54.
132.1, 133.9, 146.5, 147.0, 185.7. Anal. Calcd for C26H21
-
N3O2: C, 76.64; H, 5.19; N, 10.31. Found: C, 76.38; H, 5.44;
N 10.17.
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d s
12a ,b. To a solution of 11 (1.93 mmol) in acetone (40 mL) at
5 °C was added a precooled H2SO4 aqueous solution (3 mL,
11%) in acetone (10 mL), and the solution was stirred at room
temperature for 20 h with the reaction of 11a and 8 h with
11b. Water (40 mL) was added to the solution, which was
extracted with diethyl ether (3 × 40 mL), and the combined
organic layers were washed with a 2 N Na2CO3 aqueous
solution (3 × 50 mL) and dried over MgSO4. After filtration
and removal of the solvent, the crude product was purified by
column chromatography (hexane/ethyl acetate, 100:1).
tr a n s-1-P h en yl-2-m et h yl-1-d od ecen -5-yn e-3,4-d ion e
(12a ). This compound was obtained as a yellow oil, yield
83%: 1H NMR δ 0.89 (t, 3 H, J ) 6.8 Hz), 1.20-1.52 (m, 6 H),
1.56-1.75(m, 2 H), 2.17 (d, 3 H, J ) 0.95 Hz), 2.47 (t, 2 H, J
) 7.1 Hz), 7.40-7.53 (m, 6 H); 13C NMR δ 12.5, 13.9, 19.5,
22.4, 27.4, 28.5, 31.1, 79.8, 103.5, 128.6, 129.7, 130.2, 132.3,
134.9, 147.2, 180.8, 192.8. Anal. Calcd for C19H22O2: C, 80.82;
H, 7.85. Found: C,80.84; H, 8.23.
tr a n s-1,6-Dip h en yl-1-h exen -5-yn e-3,4-d ion e (12b): ob-
tained as yellow needles, yield 85%, mp 103-105 °C; 1H NMR
δ 7.41-7.60 (m, 7 H), 7.62-7.82 (m, 4 H), 7.94 (d, 1 H, J )
16.2 Hz); 13C NMR δ 86.6, 99.0, 118.0, 119.4, 128.7, 129.0,
131.5, 131.6, 133.7, 134.2, 148.5, 177.1, 184.5. Anal. Calcd
for C18H12O2: C, 83.06; H, 4.65. Found: C, 83.20; H, 4.64.
P r ep a r a tion of 1-P h en yl-2-m eth yl-6-ch lor o-(E,E)-1,5-
d od eca d ien e-3,4-d ion e (13) a n d 12a . To a solution of 11a
(0.83 g, 1.93 mmol) in acetone (40 mL) at 5 °C was added a
precooled HCl aqueous solution (1 mL, 37%) in acetone (10
mL), and the solution was allowed to warm to room temper-
1-(Ben zotr iazol-1-yl)-1-ph en oxy-3-ph en ylpr opan e (15d):
1
obtained as an oil; yield 71%; H NMR δ 1.50-1.68 (m, 1 H),
1.77-1.98 (m, 1 H), 2.24-2.40 (m, 1 H), 2.43-2.60 (m, 1 H),
2.60-2.78 (m 2 H), 6.82 (t, 1 H, J ) 6.9 Hz), 6.88-7.00 (m, 3
H), 7.09-7.38 (m, 8 H), 7.41 (t, 1 H, J ) 7.7 Hz), 7.75 (d, 1 H,
J ) 8.4 Hz), 8.01 (d, 1 H, J ) 7.5 Hz); 13C NMR δ 26.2, 34.1,
34.9, 88.1, 111.0, 116.2, 120.0, 122.9, 124.2, 126.0, 127.6, 128.2,
128.3, 129.6, 131.1, 141.0, 146.6, 156.0. Anal. Calcd for
C22H21N3O: C, 76.94; H, 6.16; N, 12.24. Found: C, 77.19; H,
6.40; N, 12.19.
Gen er a l P r oced u r e for th e P r ep a r a tion of 16. To a
solution of 15 (3.23 mmol) in THF (40 mL) at -78 °C was
added n-butyllithium (1.6 M in cyclohexane, 3.39 mmol), with
stirring, which was continued for 5 min before the appropriate
acid chloride (benzoyl, trimethylacetyl, 2-naphthoyl, 4-chlo-
robenzoyl, 2-toluoyl, benzoyl, or 4-chlorobenzoyl chloride, 3.39
mmol) was added. After the solution was stirred at -78 °C
for an additional 15 min, it was quenched at -78 °C with water
(40 mL). The mixture was extracted with diethyl ether (3 ×
40 mL), and the combined organic layer was dried over
anhydrous MgSO4. Evaporation of the solvent gave a residue
which was separated by column chromatography (hexane/ethyl
acetate, 30:1).
1-t er t -B u t y l-2-(b e n zo t r ia zo l-1-y l)-2-p h e n o x y -1-o c -
1
ta n on e (16b): obtained as an oil; yield 86%; H NMR δ 0.85
(t, 3 H, J ) 6.3 Hz), 1.05-1.46 (m 7 H), 1.52 (s, 9 H), 1.62-
1.80 (m, 1 H), 2.42-2.58 (m, 1 H), 6.51 (d, 2 H, J ) 7.8 Hz),
6.99 (t, 1 H, J ) 7.2 Hz), 7.11 (t, 1 H, J ) 7.7 Hz), 7.33 (t, 1 H,

4130 J . Org. Chem., Vol. 62, No. 12, 1997
Katritzky et al.
J ) 7.5 Hz), 7.41 (t, 1 H, J ) 7.7 Hz), 7.56 (d, 1 H, J ) 8.4
Hz), 8.08 (d, 1 H, J ) 8.1 Hz); 13C NMR δ 13.8, 22.3, 24.5,
27.8, 29.1, 31.1, 34.1, 45.1, 99.8, 111.8, 119.9, 120.3, 124.0,
124.3, 127.6, 129.4, 132.5, 146.3, 152.3, 205.8. Anal. Calcd
for C24H31N3O2: C, 73.25; H, 7.94; N, 10.68. Found: C, 72.87;
H, 7.75; N, 10.98.
H), 1.28-1.50 (m, 6 H), 1.52-1.65 (m, 2 H), 2.68 (t, 2 H, J )
7.2 Hz); 13C NMR δ 13.9, 22.4, 22.7, 26.0, 28.7, 31.5, 38.7, 42.0,
203.3, 207.9. Anal. Calcd for C12H22O2: C,72.68; H, 11.18.
Found: C, 72.68; H, 10.80.
1-(2-Na p h th yl)-1,2-octa n ed ion e (17c): obtained as a yel-
1
low oil; yield 52% based on 15b; H NMR δ 0.89 (t, 3 H, J )
1-(4-Ch lor op h en yl)-2-(ben zotr ia zol-1-yl)-2-p h en oxy-1-
d od eca n on e (16d ): obtained as an oil; yield 85%; 1H NMR δ
0.86 (t, 3 H, J ) 6.9 Hz), 1.10-1.50 (m, 16 H), 2.80-2.92 (m,
1 H), 3.08-3.20 (m, 1 H), 6.55 (d, 2 H, J ) 7.5 Hz), 7.03 (t, 1
H, J ) 7.4 Hz), 7.14 (t, 2 H, J ) 7.5 Hz), 7.34-7.48 (m, 4 H),
7.59 (d, 1 H, J ) 7.5 Hz), 8.00 (d, 2 H, J ) 8.7 Hz), 8.10 (d, 1
H, J ) 7.2 Hz); 13C NMR δ 14.1, 22.6, 23.2, 29.0, 29.2, 29.3,
29.4, 31.8, 34.3, 97.9, 112.0, 120.2, 120.5, 124.6, 124.7, 128.2,
129.0, 129.7, 131.3, 132.7, 140.3, 146.5, 152.3, 191.1. Anal.
Calcd for C30H34N3O2Cl: C, 71.48; H, 6.80; N, 8.34. Found:
C, 71.70; H, 6.92; N, 8.83.
1,5-Dip h en yl-2-(b en zot r ia zol-1-yl)-2-p h en oxy-5-p en -
ta n on e (16f): obtained as an oil; yield 84%; 1H NMR δ 1.72-
1.95 (m, 2 H), 2.45-2.70 (m, 2 H), 2.90-3.05 (m, 1 H), 3.18-
3.32 (m, 1 H), 6.52 (d, 2 H, J ) 7.5 Hz), 7.00 (m, 3 H), 7.05-
7.25 (m, 5 H), 7.28-7.48 (m, 4 H), 7.52 (t, 1 H, J ) 7.4 Hz),
7.61 (d, 1 H, J ) 8.1 Hz), 8.01 (d, 2 H, J ) 7.8 Hz), 8.09 (d, 1
H, J ) 7.5 Hz); 13C NMR δ 24.6, 33.7, 35.1, 97.7, 112.0, 120.0,
120.5, 124.4, 124.5, 125.8, 128.1, 128.2, 128.5, 129.5, 129.7,
132.6, 133.5, 134.2, 140.6, 146.4, 152.2, 191.9. Anal. Calcd
for C29H25N3O2: C, 77.83; H, 5.63; N, 9.39. Found: C, 77.54;
H, 5.79; N, 9.26.
Gen er a l P r oced u r e for th e P r ep a r a tion of 17. To a
solution of 16 (2.88 mmol) in acetic acid (22 mL) was added a
solution of sulfuric acid (2.2 mL, 95-98%) in water (11 mL),
and the solution was refluxed for 13.5 h under N2. Water (30
mL) was added to the solution, which was extracted with
diethyl ether (3 × 50 mL), and the combined organic layers
were washed with a 2 N Na2CO3 aqueous solution (3 × 40 mL)
and dried over MgSO4. After filtration and removal of the
solvent, the crude product was obtained as a yellow oil, which
was purified by column chromatography (hexane/ethyl acetate,
30:1) to give the corresponding 1,2-diketone.
6.8 Hz), 1.15-1.55 (m, 6 H), 1.68-1.82 (m, 2 H), 2.94 (t, 2 H,
J ) 7.4 Hz), 7.52-7.70 (m, 2 H), 7.85-8.10 (m, 4 H), 8.52 (s,
1 H); 13C NMR δ 14.0, 22.5, 22.9, 28.9, 31.5, 38.9, 124.2, 127.0,
127.9, 128.9, 129.3, 129.4, 130.0, 132.3, 133.5, 136.2, 192.5,
203.7. Anal. Calcd for C18H20O2: C, 80.56; H, 7.51. Found:
C, 80.29; H, 7.55.
1-(4-Ch lor op h en yl)-1,2-d od eca n ed ion e (17d ): obtained
as yellow prisms, yield 91%, mp 45-47 °C; 1H NMR δ 0.87 (t,
3 H, J ) 6.6 Hz), 1.20-1.42 (m, 14 H), 1.60-1.75 (m, 2 H),
2.86 (t, 2 H, J ) 7.2 Hz), 7.45 (d, 2 H, J ) 8.4 Hz), 7.94 (d, 2
H, J ) 8.4 Hz); 13C NMR δ 14.1, 22.6, 22.9, 29.1, 29.3, 29.4,
29.5, 31.8, 38.6, 129.2, 130.5, 131.5, 141.2, 190.6. 202.7. Anal.
Calcd for C18H25O2Cl: C, 70.00; H, 8.16. Found: C, 69.98; H,
8.13.
1-(2-Meth ylp h en yl)-1,2-d od eca n ed ion e (17e): obtained
1
as a yellow oil; yield 72% based on 15c; H NMR δ 0.89 (t, 3
H, J ) 6.6 Hz), 1.20-1.43 (m, 14 H), 1.65-1.78 (m, 2 H), 2.56
(s, 2 H, J ) 7.4 Hz), 7.26-7.32 (m, 2 H), 7.44 (d, 1 H, J ) 6.3
Hz), 7.58 (d, 1 H, J ) 8.1 Hz); 13C NMR δ 14.1, 21.4, 22.6,
22.9, 29.1, 29.2, 29.3, 29.4, 29.5, 31.9, 38.5, 125.7, 131.3, 132.0,
132.2, 133.1, 140.8. 195.6, 203.8; HRMS (EI) calcd for C19H28O2
(M+) 288.2089, found 288.2019.
1,5-Dip h en yl-1,2-p en ta n ed ion e (17f): obtained as a yel-
1
low oil; yield 92%; H NMR δ 2.04 (quintet, 2 H, J ) 7.5 Hz),
2.70 (t, 2 H, J ) 7.5 Hz), 2.90 (t, 2 H, J ) 7.5 Hz), 7.16-7.35
(m, 5 H), 7.47 (t, 2 H, J ) 7.5 Hz), 7.62 (t, 1 H, J ) 7.4 Hz),
7.95 (d, 2 H, J ) 7.2 Hz); 13C NMR δ 24.4, 35.1, 38.0, 126.1,
128.4, 128.8, 130.1, 131.9, 134.5, 141.1, 192.2, 202.9. Anal.
Calcd for C17H16O2: C, 80.93; H, 6.39. Found: C, 80.49; H,
6.58.
1-(4-Ch lor op h en yl)-5-p h en yl-1,2-p en t a n ed ion e (17g):
1
1-P h en yl-1,2-h ep ta n ed ion e (17a ): obtained as a yellow
obtained as a yellow oil; yield 72% based on 15d ; H NMR δ
1
oil; yield 56% based on 15a ; H NMR δ 0.92 (t, 3 H, J ) 7.1
2.03 (quintet, 2 H, J ) 7.5 Hz), 2.70 (t, 2 H, J ) 7.5 Hz), 2.89
(t, 2 H, J ) 7.5 Hz), 7.12-7.35 (m, 5 H), 7.44 (d, 2 H, J ) 8.7
Hz), 7.91 (d, 2 H, J ) 9.0 Hz); 13C NMR δ 24.4, 35.0, 37.8,
126.1, 128.5, 129.2, 130.3, 131.6, 141.0, 141.2, 190.4, 202.2.
Anal. Calcd for C17H15O2Cl: C, 71.21; H, 5.27. Found: C,
70.94; H, 5.34.
Hz), 1.30-1.50 (m, 4 H), 1.64-1.80 (m, 2 H), 2.89 (t, 2 H, J )
7.4 Hz), 7.50 (t, 2 H, J ) 7.5 Hz), 7.62 (t, 1 H, J ) 7.4 Hz),
7.99 (d, 2 H, J ) 8.4 Hz); 13C NMR δ 13.8, 22.3, 22.5, 31.3,
38.7, 128.8, 130.1, 132.0, 134.5, 192.5, 203.4. Anal. Calcd for
C13H16O2: C, 76.44; H, 7.90. Found: C, 76.07; H, 7.56.
1-ter t-Bu tyl-1,2-octa n ed ion e (17b): obtained as a yellow
1
oil; yield 83%; H NMR δ 0.92 (t, 3 H, J ) 6.5 Hz), 1.27 (s, 9
J O970092J