Regioselective synthesis of pentasubstituted benzene derivatives: TBAF as an effective catalyst for the sequential Michael addition-intramolecular aldolization

Article abstract of DOI:10.1016/j.tetlet.2006.06.180

Polysubstituted benzene derivatives were synthesized starting from the Baylis-Hillman adducts via the sequential introduction of primary nitroalkane at the primary position, Michael addition to β-branched Michael acceptor, aldol condensation, elimination

Full text of DOI:10.1016/j.tetlet.2006.06.180

Tetrahedron Letters 47 (2006) 6641–6645
Regioselective synthesis of pentasubstituted benzene derivatives:
TBAF as an effective catalyst for the sequential Michael
addition-intramolecular aldolization
Da Yeon Park, Saravanan Gowrisankar and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
Received 1 June 2006; revised 27 June 2006; accepted 30 June 2006
Available online 28 July 2006
Abstract—Polysubstituted benzene derivatives were synthesized starting from the Baylis–Hillman adducts via the sequential intro-
duction of primary nitroalkane at the primary position, Michael addition to b-branched Michael acceptor, aldol condensation, elim-
ination of nitrous acid, and the final aromatization process.
Ó 2006 Elsevier Ltd. All rights reserved.
Recently, we reported the synthesis of polysubstituted
benzene and pyridine derivatives from Baylis–Hillman
adducts.1,2 The synthetic pathway for the benzene deriv-
ative, as an example, is depicted in Scheme 1.1 As shown
the reaction followed sequential introduction of primary
nitroalkane at the primary position of the Baylis–Hill-
man adduct, Michael addition, aldol condensation,
elimination of nitrous acid, and the final aromatization
process.1
could be synthesized easily including tetralone deriva-
tives4 (vide infra).
Thus, we examined the reaction of 2a and chalcone (3a),
as the representative b-substituted Michael acceptor, un-
der various conditions. The reactions did not give appre-
ciable yields of the Michael addition product nor the
cyclized intermediate 4a under the conditions including
DBU/THF, DBU/CH3CN, K2CO3/CH3CN, K2CO3/
DMF, and Cs2CO3/DMF.5 Fortunately, we could
obtain the cyclized intermediate 4a as diastereomeric
mixtures in 80% yield when we used TBAF (n-tetrabutyl-
ammonium fluoride) as the catalyst in THF.6–8
Although we did not separate each isomer of 4a in pure
states, we could confirm the structure of 4a by carrying
out the next step (vide infra). The crude mixtures of 4a
under the influence of p-TsOH (10 mol %) in benzene
at refluxing temperature for 10 min afforded 5a as two
isomeric mixtures (syn/anti) in 56% yield. The reaction
Based both on the importance and difficulties of regio-
selective synthesis of polysubstituted benzene deriva-
tives,1,3 we intended to extend our protocol to the
synthesis of pentasubstituted benzene derivatives by
using b-substituted Michael acceptors. We reasoned that
if the sequential Michael addition-intramolecular aldol-
ization steps could occur successfully with b-substituted
Michael acceptor, other steps would proceed as before
and pentasubstituted benzene derivatives (Scheme 2)
R1
HO
R1
R1
R2
OAc R1
EWG
EWG
EWG
Ph
O
Ph
Ph
Ph
O
NO2
R2 NO2
R2
Scheme 1.
Keywords: Polysubstituted benzenes; Baylis–Hillman adducts; TBAF; Michael acceptor.
*
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389; e-mail: kimjn@chonnam.ac.kr
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.180

6642
D. Y. Park et al. / Tetrahedron Letters 47 (2006) 6641–6645
O
OH
CH3CH2NO2
K2CO3, DMF
n
-Bu4NF (0.4 equiv)
OAc
COPh
Ph
Ph
O
THF, reflux, 2 h
Ph
Ph
Ph
O
Ph
NO2
NO2
1a
2a
3a
4a (80%, crude yield)
p
-TsOH (10 mol%)
PhH, reflux, 10 min
K2CO3 (3.0 equiv)
DMF, 120-130 oC, 7 h
86%
O
COPh
Ph
Ph
Ph
Ph
Ph
NO2
5a (56% from 2a + 3a)
6a
Scheme 2.
of 5a and K2CO3 (3 equiv) in DMF at around 120–
130 °C for 7 h gave the desired final pentasubstituted
benzene 6a in 86% yield (Scheme 2).9
marized in Table 1. We observed in all cases the forma-
tion of variable ratios of diastereomeric mixtures 4,
which appeared just below the starting materials 2 on
TLC. We separated the diastereomeric mixtures 4 alto-
gether by column chromatography and used for the next
dehydration step. After dehydration we could obtain the
corresponding cyclohexene derivatives 5b–e in 27–71%
Encouraged by the results we carried out the reactions
of 2a–c with chalcone (3a), 4-phenyl-3-buten-2-one
(3b), and ethyl cinnamate (3c) and the results are sum-
Table 1. Synthesis of polysubstituted benzene derivatives
Entry
Substrate
Michael acceptor Conditions
Cyclohexenone (%)a
Conditions Product (%)
K2CO3
O
COPh
Ph
1. n-Bu4NF (0.4 equiv)
COPh
Ph
Ph
O
Ph
(3.0 equiv)
DMF, 120–
130 °C, 7 h
5a (70)
THF, reflux, 2 h;
Ph
1
2. column (4a, 80%);
3. p-TsOH (10 mol %)
PhH, reflux, 10 min
Ph
NO2
2a
Ph
Ph
3a
6a (86)
NO2
O
COMe
Ph
COMe
Ph
Ph
Ph
Ph
2
3
2a
1. n-Bu4NF (0.4 equiv)
THF, reflux, 20 h;
2. column (4b, 87%);
3. p-TsOH (10 mol %)
PhH, reflux, 10 min
K2CO3
(3.0 equiv)
DMF, 120–
130 °C, 5 h
6b (71)b
3b
5b (71)
NO2
COMe
Ph
COMe
Ph
Ph
Ph
O
Ph
Ph
3b
1. n-Bu4NF (0.4 equiv)
THF, reflux, 8 h;
K2CO3
(3.0 equiv)
6c (74)b
2b
5c (67) DMF, 120–
130 °C, 3 h
NO2
2. column (4c, 73%);
3. p-TsOH (10 mol %)
PhH, reflux, 120 min
NO2
COMe
Ph
COMe
Ph
Ph
Ph
O
4
5
3b
1. n-Bu4NF (1.0 equiv)
THF, rt, 48 h; 2. column
(4d, 35%); 3. p-TsOH
(10 mol %) PhH, reflux,
10 min
K2CO3
(3.0 equiv)
DMF, 120–
130 °C, 4 h
6d (75)b
2c
5d (44)
NO2
NO2
O
COOEt
Ph
COOEt
Ph
Ph
OEt
2a
1. n-Bu4NF (1.0 equiv)
THF, reflux, 18 h;
2. column (4e, 46%);
3. p-TsOH (10 mol %)
PhH, reflux, 24 h
K2CO3
(3.0 equiv)
DMF, 120–
130 °C, 3 h
Ph
3c
5e (27)
6e (71)
NO2
Mixtures of syn/anti were used in the next step without separation. We isolated one major isomer of 5a and identified the structure.8
The oxidized benzoyl derivatives were obtained in 3% (entry 2), 3% (entry 3), and 6% (entry 4), respectively.
a
b

D. Y. Park et al. / Tetrahedron Letters 47 (2006) 6641–6645
6643
yields as cis/trans mixtures. The final step (elimination
of HNO2 and concomitant aromatization) proceeded
effectively in all cases in good yields (71–75%). We ele-
vated the reaction temperature sufficiently (120–
130 °C) in order to convert both isomers (syn/anti) of
5b–e into the final benzene derivatives 6b–e (vide infra).
In some cases, we observed the oxidized compounds
7b–d (entries 2–4) in small amounts.
results of the next elimination step. The elimination of
nitrous acid was fast (rt, <90 min) for 5f-cis, while rela-
tively slow for 5f-trans (heating, 5 h). The elimination of
HNO2 for 5f-cis must occur via the facile anti-periplanar
state.10 The elimination of HNO2 from 5f-trans must
occur by following the difficult syn-elimination mode.
It is noteworthy that an appreciable amount of oxidized
benzoyl derivative 7f was generated during the elimina-
tion stage.
Similarly, we could obtain 6f from the reaction of 2a and
ethyl 4,4,4-trifluorocrotonate (3d) as in Scheme 3. In this
case, we could separate the cis and trans isomers 5f-cis
and 5f-trans in 26% and 31%, respectively.9 The struc-
tures of 5f-cis and 5f-trans were supposed from the
As a next trial, we examined the reaction of 2a and
2-cyclohexen-1-one (3e) for the synthesis of tetralone
derivative. As shown in Scheme 4, we could synthesize
desired compound 6g in moderate yield by following
OH
O
(1)
n
-Bu4NF (1.0 equiv)
COOEt
CF3
Ph
THF, reflux, 30 h
OEt
2a
+
(2) column
F3C
NO2
3d
4f (52%, crude yield)
p
-TsOH (10 mol%)
PhH, reflux, 5 h
COOEt
CF3
COOEt
CF3
Ph
Ph
+
NO2
NO2
5f-cis (26%)
5f-trans (31%)
K2CO3 (3.0 equiv)
DMF, rt, 90 min
K2CO3 (3.0 equiv)
DMF, 80-90 oC, 5 h
O
6f (62%) + 7f (10%)
COOEt
CF3
COOEt
CF3
Ph
Ph
6f (51%)
7f (17%)
Scheme 3.
1.
n
-Bu4NF (0.4 equiv)
THF, rt, 24 h
2. column
3. -TsOH (20 mol%)
O
O
p
Ph
O
Ph
PhH, reflux, 5 h
+
R2 NO2
R2
NO2
3e
5g: R2 = Me, 58%
5h: R2 = Et, 37%
2a: R2 = Me
2c: R2 = Et
K2CO3 (3.0 equiv)
DMF, 120-130 oC, 4 h
O
Ph
6g: R2 = Me, 81%
6h: R2 = Et, 71%
R2
Scheme 4.

6644
D. Y. Park et al. / Tetrahedron Letters 47 (2006) 6641–6645
their synthesis of bicyclo[3.3.1]nonenols by the sequential
Michael addition-intramolecular aldolization process with
TBAF: (a) Aoyagi, K.; Nakamura, H.; Yamamoto, Y. J.
Org. Chem. 1999, 64, 4148; (b) Nakamura, H.; Aoyagi, K.;
Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 1167.
the same protocol. The reaction of 2c and 3e showed
similar reactivity and we synthesized 6h similarly.9
In summary, we disclosed the synthesis of pentasubsti-
tuted benzene derivatives regioselectively starting from
the Baylis–Hillman adducts via the sequential introduc-
tion of primary nitroalkane at the primary position,
Michael addition with TBAF, aldol condensation,
elimination of nitrous acid, and the final aromatization
process.
8. For the leading references on the Michael reaction involv-
ing b-substituted Michael acceptors, see: (a) Shankar, R.;
Jha, A. K.; Singh, U. S.; Hajela, K. Tetrahedron Lett. 2006,
47, 3077; (b) Correc, O.; Guillou, K.; Hamelin, J.; Paquin,
L.; Texier-Boullet, F.; Toupet, L. Tetraheron Lett. 2004,
45, 391; (c) Geirsson, J. K. F.; Arnadottir, L.; Jonsson, S.
Tetrahedron 2004, 60, 9149; (d) Xuan, J. X.; Fry, A. J.
Tetrahedron Lett. 2001, 42, 3275; (e) Hoashi, Y.; Yabuta,
T.; Takemoto, Y. Tetrahedron Lett. 2004, 45, 9185.
Acknowledgements
9. Spectroscopic data of prepared compounds are as follows:
Compound 5a (pure single isomer, unknown stereochem-
istry): yellow solid, mp 213–214 °C; IR (KBr) 3059, 1641,
This work was supported by the Korea Research Foun-
dation Grant funded by the Korean Government
(MOEHRD) (KRF-2005-041-C00248). Spectroscopic
data were obtained from the Korea Basic Science Insti-
tute, Gwangju branch.
1537, 1342, 1273 cmÀ1 1H NMR (CDCl3, 300 MHz) d
;
1.31 (s, 1H), 1.94 (d, J = 1.2 Hz, 3H), 2.53 (dd, J = 16.8
and 2.7 Hz, 1H) 3.64 (d, J = 16.8 Hz, 1H) 4.75 (s, 1H),
6.98 (d, J = 2.7 Hz, 1H), 7.25–7.73 (m, 15H); 13C NMR
(CDCl3, 75 MHz) d 17.29, 26.28, 32.76, 50.56, 89.87,
127.40, 128.06, 128.40, 128.60, 128.66, 129.20, 129.24,
129.99, 132.43, 133.26, 134.56, 135.49, 136.18, 136.81,
136.87, 198.10; LCMS m/z 376 (M+ÀHNO2).
References and notes
1. (a) Lee, M. J.; Lee, K. Y.; Park, D. Y.; Kim, J. N.
Tetrahedron 2006, 62, 3128; (b) Lee, M. J.; Lee, K. Y.;
Gowrisankar, S.; Kim, J. N. Tetrahedron Lett. 2006, 47,
1355.
Compound 5f-cis: 26%; colorless oil; IR (film) 2985, 1716,
1554, 1350, 1246 cmÀ1 1H NMR (CDCl3, 300 MHz) d
;
1.37 (t, J = 7.2 Hz, 3H), 1.56 (s, 1H), 2.37 (s, 1H), 3.13 (d,
J = 17.0 Hz, 1H), 3.56 (d, J = 17.0 Hz, 1H), 4.26–4.43 (m,
3H), 7.20 (d, J = 2.4 Hz, 1H), 7.33–7.47 (m, 5H); 13C
NMR (CDCl3, 75 MHz) d 14.12, 16.40, 26.51, 29.69,
32.53, 49.24 (q, J = 26.9 Hz, 1C), 61.61, 84.13, 124.56 (q,
J = 282.2 Hz, 1C), 128.43, 128.68, 129.60, 132.54, 135.58,
135.70, 144.85, 167.17; LCMS m/z 383 (M+).
2. (a) Park, D. Y.; Lee, M. J.; Kim, T. H.; Kim, J. N.
Tetrahedron Lett. 2005, 46, 8799; (b) Lee, M. J.; Kim, S.
C.; Kim, J. N. Bull. Korean Chem. Soc. 2006, 27, 439.
3. (a) Bi, X.; Dong, D.; Liu, Q.; Pan, W.; Zhao, L.; Li, B. J.
Am. Chem. Soc. 2005, 127, 4578; (b) Barun, O.; Nandi, S.;
Panda, K.; Ila, H.; Junjappa, H. J. Org. Chem. 2002, 67,
5398; (c) Ballini, R.; Barboni, L.; Fiorini, D.; Giarlo, G.;
Palmieri, A. Chem. Commun. 2005, 2633; (d) Saito, S.;
Yamamoto, Y. Chem. Rev. 2000, 100, 2901; (e) Asao, N.;
Nogami, T.; Lee, S.; Yamamoto, Y. J. Am. Chem. Soc.
2003, 125, 10921; (f) Asao, N.; Takahashi, K.; Lee, S.;
Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002,
124, 12650; (g) Asao, N.; Aikawa, H.; Yamamoto, Y. J.
Am. Chem. Soc. 2004, 126, 7458; (h) Langer, P.; Bose, G.
Angew. Chem., Int. Ed. 2003, 42, 4033; (i) Katritzky, A. R.;
Li, J.; Xie, L. Tetrahedron 1999, 55, 8263, and further
references cited in Ref. 1a.
4. For the synthesis and synthetic applicability of tetralone
derivatives, see: (a) Zhang, L.; Kozmin, S. A. J. Am.
Chem. Soc. 2004, 126, 10204; (b) Gray, A. D.; Smyth, T. P.
J. Org. Chem. 2001, 66, 7113; (c) Nguyen, P.; Corpuz, E.;
Heidelbaugh, T. M.; Chow, K.; Garst, M. E. J. Org.
Chem. 2003, 68, 10195; (d) Uenoyama, Y.; Tsukida, M.;
Doi, T.; Ryu, I.; Studer, A. Org. Lett. 2005, 7, 2985; (e)
Vargas, A. C.; Quiclet-Sire, B.; Zard, S. Z. Org. Lett. 2003,
5, 3717; (f) Taber, D. F.; Neubert, T. D.; Rheingold, A. L.
J. Am. Chem. Soc. 2002, 124, 12416.
Compound 5f-trans: 31%; colorless oil; IR (film) 2985,
1716, 1551, 1342, 1250, 1152 cmÀ1 1H NMR (CDCl3,
;
300 MHz) d 1.35 (t, J = 7.2 Hz, 3H), 1.77 (d, J = 1.8 Hz,
3H), 2.29 (s, 3H), 2.95 (dd, J = 18.0 and 3.3 Hz, 1H), 3.71
(d, J = 18.0 Hz, 1H), 4.22–4.40 (m, 2H), 4.88 (q,
J = 11.0 Hz, 1H), 4.88 (q, J = 11.0 Hz, 1H), 7.07 (s, 1H),
7.30–7.45 (m, 5H); 13C NMR (CDCl3, 75 MHz) d 14.07,
16.82, 25.74, 34.02, 46.76 (q, J = 26.9 Hz, 1C), 61.34,
87.28, 120.03, 125.05 (q, J = 279.6 Hz, 1C), 127.95,
128.56, 129.18, 131.93, 133.45, 136.30, 145.25, 167.01.
Compound 6a: 86%; colorless oil; IR (film) 3059, 2924,
1
1670, 1450 cmÀ1; H NMR (CDCl3, 300 MHz) d 2.05 (s,
6H), 4.05 (s, 2H), 7.05–7.55 (m, 16H); 13C NMR (CDCl3,
75 MHz) d 16.23, 19.90, 39.25, 126.09, 126.75, 127.58,
128.11, 128.50, 128.74, 129.15, 130.20, 132.34, 132.71,
133.72, 137.89, 138.28, 138.46, 138.66, 140.19, 140.73,
200.22; LCMS m/z 376 (M+). Anal. Calcd for C28H24O: C,
89.33; H, 6.43. Found: C, 89.42; H, 6.55.
Compound 6b: 71%; white solid, mp 86–88 °C; IR (film)
3024, 1697, 1493, 1450 cmÀ1; 1H NMR (CDCl3, 300 MHz)
d 1.91 (s, 3H), 2.06 (s, 3H), 4.01 (s, 2H), 7.05 (s, 1H), 7.16–
7.41 (m, 10H); 13C NMR (CDCl3, 75 MHz) d 15.82, 19.95,
32.46, 39.39, 126.09, 127.34, 128.23, 128.42, 128.49,
128.74, 130.06, 132.07, 133.56, 135.42, 138.70, 138.87,
139.92, 143.58, 208.39.
5. We observed the formation of a diastereomeric mixture of
4a in less than 20% in all cases.
6. For the usefulness of n-tetrabutylammonium fluoride as
the catalyst of Michael reaction, see: (a) Ooi, T.; Doda, K.;
Maruoka, K. J. Am. Chem. Soc. 2003, 125, 9022; (b)
Sharma, G. V. M.; Reddy, V. G.; Chander, A. S.; Reddy,
K. R. Tetrahedron: Asymmetry 2002, 13, 21; (c) Matsu-
moto, K. Angew. Chem., Int. Ed. Engl. 1981, 20, 770; (d)
Li, W.-S.; Thottathil, J.; Murphy, M. Tetrahedron Lett.
1994, 35, 6591; (e) Jenner, G. New J. Chem. 1999, 23,
525.
Compound 7b (2-acetyl-4-benzoyl-3,6-dimethylbiphenyl):
3%; colorless oil; IR (film) 2924, 1701, 1666, 1239 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 1.95 (s, 3H), 2.12 (s, 3H),
2.16 (s, 3H), 7.22–7.91 (m, 11H); 13C NMR (CDCl3,
75 MHz) d 16.53, 19.97, 32.19, 127.85, 128.18, 128.45,
128.63, 129.51, 129.76, 130.21, 133.56, 133.67, 137.25,
138.14, 138.96, 139.14, 143.99, 198.41, 207.24.
Compound 6c: 74%; colorless oil; IR (film) 3060, 2966,
7. Yamamoto and co-workers reported the effective catalytic
activity of n-tetrabutylammonium fluoride (TBAF) in
1697, 1452 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.11
;
(t, J = 7.5 Hz, 3H), 1.90 (s, 2H), 2.04 (s, 2H), 2.54

D. Y. Park et al. / Tetrahedron Letters 47 (2006) 6641–6645
6645
(q, J = 7.5 Hz, 2H), 4.05 (s, 2H), 7.02 (s, 1H), 7.17–7.39
(m, 10H); 13C NMR (CDCl3, 75 MHz) d 15.71, 19.95,
23.15, 32.57, 38.25, 126.05, 127.29, 128.86, 128.77, 130.12,
132.48, 133.61, 134.80, 135.51, 138.08, 138.86, 140.51,
143.32, 207.82; LCMS m/z 328 (M+).
Compound 6f: 51%; colorless oil; IR (film) 2985, 1736,
1454, 1304, 1203, 1122 cmÀ1; 1H NMR (CDCl3, 300 MHz)
d 1.36 (t, J = 7.2 Hz, 3H), 2.15 (s, 3H), 2.42 (d, J = 2.4 Hz,
3H), 3.99 (s, 2H), 4.39 (q, J = 7.2 Hz, 2H), 7.07–7.32 (m,
6H); 13C NMR (CDCl3, 75 MHz) d 13.95, 15.72, 19.91 (q,
J = 3.1 Hz, 1 C), 39.44, 61.74, 122.47, 123.77, 124.94 (q,
J = 277.0 Hz, 1C), 126.41, 128.64, 131.33, 133.75, 134.50,
134.97, 138.74, 143.09, 168.99. Anal. Calcd for
C19H19F3O2: C, 67.85; H, 5.69. Found: C, 67.59; H, 5.88.
Compound 7f: 17%; colorless oil; IR (film) 2987, 1736,
Compound 7c (2-acetyl-4-benzoyl-3-ethyl-6-methylbiphen-
yl): 3%; colorless oil; IR (film) 2925, 1699, 1667,
1447 cmÀ1 1H NMR (CDCl3, 300 MHz) d 1.07 (t, J =
;
4.5 Hz, 3H), 1.95 (s, 3H), 2.10 (s, 3H), 2.57 (q, J = 4.5 Hz,
2H), 7.17 (s, 1H), 7.23–7.63 (m, 9H), 7.89 (d, J = 4.8 Hz,
2H); 13C NMR (CDCl3, 75 MHz) d 16.66, 20.02, 23.48,
32.55, 127.82, 128.44, 128.54, 129.74, 129.87, 130.31,
133.51, 135.35, 137.37, 138.23, 138.74, 139.01, 143.71,
198.31, 206.93.
1674, 1450, 1369, 1246, 1130 cmÀ1 1H NMR (CDCl3,
;
300 MHz) d 1.38 (t, J = 7.2 Hz, 3H), 2.18 (s, 3H), 2.50 (s,
3H), 4.41 (q, J = 7.2 Hz, 2H), 7.22 (s, 1H), 7.46–7.51 (m,
2H), 7.60–7.66 (m, 1H), 7.78–7.81 (m, 2H); 13C NMR
(CDCl3, 75 MHz) d 13.94, 16.31, 19.97 (q, J = 2.9 Hz,
1C), 62.04, 123.84 (q, J = 273.8 Hz, 1C), 126.58 (q,
J = 29.7 Hz, 1C), 128.84, 130.08, 130.69, 131.29, 134.07,
134.52 (q, J = 2.9 Hz, 1C), 135.14 (q, J = 1.7 Hz, 1C),
136.37, 142.91, 167.97, 196.88.
Compound 6d: 75%; colorless oil; IR (film) 3059, 2966,
1
1697, 1454 cmÀ1; H NMR (CDCl3, 300 MHz) d 0.99 (t,
J = 7.5 Hz, 3H), 1.92 (s, 3H), 2.11 (s, 3H), 2.40 (q,
J = 7.5 Hz, 2H), 4.03 (s, 2H), 7.08 (s, 1H), 7.16–7.40 (m,
10H); 13C NMR (CDCl3, 75 MHz) d 15.59, 15.82, 25.83,
32.48, 39.54, 126.06, 127.32, 128.08, 128.25, 128.45,
128.70, 130.26, 130.58, 134.90, 138.55, 138.86, 139.92,
142.72, 208.47.
Compound 6g: 81%; white solid, mp 68–70 °C; IR (film)
2939, 1678, 1454 cmÀ1 1H NMR (CDCl3, 300 MHz) d
;
2.09 (q, J = 6.3 Hz, 2H), 2.24 (s, 3H), 2.46 (s, 3H), 2.63(t,
J = 6.3 Hz, 2H), 2.81 (t, J = 6.3 Hz, 2H), 4.00 (s, 2H),
7.07–7.28 (m, 6H); 13C NMR (CDCl3, 75 MHz) d 17.34,
19.61, 22.50, 27.19, 39.48, 40.88, 125.90, 128.36, 128.44,
132.95, 133.04, 136.01, 136.71, 137.79, 140.34, 141.80,
201.59; LCMS m/z 264 (M+). Anal. Calcd for C19H20O: C,
86.32; H, 7.63. Found: C, 86.20; H, 7.78.
Compound 7d (2-acetyl-4-benzoyl-6-ethyl-3-methylbiphen-
yl): 6%; colorless oil; IR (film) 3062, 2962, 1701, 1666,
1450 cmÀ1
; d 1.01 (t,
1H NMR(CDCl3, 300 MHz)
J = 7.5 Hz, 3H), 1.95 (s, 3H), 2.16 (s, 3H), 2.44 (q,
J = 7.5 Hz, 2H), 7.23–7.90 (m, 11H); 13C NMR (CDCl3,
75 MHz) d 15.33, 16.53, 25.82, 32.23, 127.82, 127.97,
128.13, 128.31, 128.63, 129.97, 130.25, 133.55, 137.28,
137.83, 138.47, 139.29, 139.80, 144.16, 198.47, 207.39.
Compound 6e: 71%; colorless oil; IR (film) 2978, 1725,
Compound 6h: 71%; colorless oil; IR (film) 2962, 1677,
1453 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 1.18 (t,
J = 7.8 Hz, 3H), 2.08 (q, J = 6.3 Hz, 2H), 2.44 (s, 3H),
2.62 (q, J = 7.8 Hz, 2H), 2.64 (t, J = 6.3 Hz, 2H), 2.87 (t,
J = 6.3 Hz, 2H), 4.03 (s, 2H), 7.08–7.29 (m, 6H); 13C
NMR (CDCl3, 75 MHz) d 14.63, 17.43, 22.60, 25.98,
26.45, 39.71, 40.86, 125.93, 128.40, 128.47, 133.31, 134.51,
136.81, 138.08, 138.86, 140.38, 141.22, 201.68.
1
1282, 1188 cmÀ1; H NMR (CDCl3, 300 MHz) d 0.89 (t,
J = 7.2 Hz, 3H), 2.05 (s, 3H), 2.20 (s, 3H), 3.91 (q,
J = 7.2 Hz, 2H), 4.01 (s, 2H), 7.06 (s, 1H), 7.16–7.38 (m,
10H); 13C NMR (CDCl3, 75 MHz) d 13.63, 16.14, 20.02,
39.37, 60.67, 126.06, 127.06, 127.87, 128.46, 128.75,
129.46, 130.13, 132.57, 133.63, 135.60, 137.25, 138.33,
139.34, 139.93, 170.01. Anal. Calcd for C24H24O2: C,
83.69; H, 7.02. Found: C, 83.61; H, 7.24.
10. Smith, M. B.; March, J. In March’s Advanced Organic
Chemistry, 5th ed.; John Wiley & Sons: New York, 2001;
pp 1300–1306.