1,2- vs 1,4-Addition of acylbenzotriazoles to α,β-unsaturated aldehydes and ketones. A novel route to 3-alkyl-4,6-diaryl-3,4-dihydropyran-2-ones

Article abstract of DOI:10.1021/jo011082s

Lithiation of aliphatic 1-acylbenzotriazoles with subsequent reaction with α,β-unsaturated ketones and aldehydes affords either 3,4,6-trisubstituted 3,4-dihydropyran-2-ones or 1,3-dienes depending on the carbonyl reagent used. Substituent effects on product yield and isomer ratio are discussed.

Full text of DOI:10.1021/jo011082s

3104
J . Org. Chem. 2002, 67, 3104-3108
1,2- vs 1,4-Ad d ition of Acylben zotr ia zoles to r,â-Un sa tu r a ted
Ald eh yd es a n d Keton es. A Novel Rou te to
3-Alk yl-4,6-d ia r yl-3,4-d ih yd r op yr a n -2-on es
Alan R. Katritzky* and Olga V. Denisko
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received November 16, 2001
Lithiation of aliphatic 1-acylbenzotriazoles with subsequent reaction with R,â-unsaturated ketones
and aldehydes affords either 3,4,6-trisubstituted 3,4-dihydropyran-2-ones or 1,3-dienes depending
on the carbonyl reagent used. Substituent effects on product yield and isomer ratio are discussed.
In tr od u ction
lecular cyclization of the organolithium intermediates 2,
prepared by 1,2-addition of lithium enolates of N-acyl-
benzotriazoles 1 to carbonyl compounds (Scheme 1). This
reaction was demonstrated for nonbranched aliphatic (R1
) Et, n-C6H13) and arylalkyl (R1 ) PhCH2) acylbenzo-
triazoles, while aliphatic ketones and alkyl (arylalkyl)
aldehydes were used as carbonyl components. No reac-
tions with aromatic or R,â-unsaturated aldehydes or ke-
tones and no reactions of benzylic (R1 ) aryl) or branched
aliphatic acylbenzotriazoles were mentioned.
As in Schick’s reaction, 1,4-addition of lithiated acyl-
benzotriazoles 1 to chalcones should generate a reactive
enolate anion 5, which could attack intramolecularly the
amide carbonyl group with elimination of benzotriazolyl
anion and formation of the corresponding 3,4-dihydro-
pyran-2-ones 6 and/or 7. We have now found that lith-
iated 1-alkylcarbonylbenzotriazoles indeed provide a
convenient approach to such compounds and extend the
variety of accessible 3,4-dihydropyran-2-ones.
Reported ring syntheses of 3,4-dihydro-2-pyrones1 in-
clude (i) acid-catalyzed intramolecular cyclization of
δ-oxoalkanoic acids,2 (ii) dimerization of R,â-unsaturated
acyl cyanides3 or R-(sulfonio)ketone triflates,4 and (iii) [4
+ 2] cycloaddition of ketenes prepared in situ to diverse
R,â-unsaturated ketones.5 A few nucleophilic Michael
additions of metalated esters to R,â-unsaturated carbonyl
compounds were also reported to form 3,4-dihydro-2-
pyrones.6 However, despite extensive investigation of the
chemistry of partially reduced 2-pyrones, apparently no
3-alkyl-4,6-diaryl-3,4-dihydropyran-2-ones have been syn-
thesized.
Nucleophilic additions to conjugated unsaturated sys-
tems have been the subject of numerous studies and have
been comprehensively reviewed.7 The influence of the
nature of the nucleophile, temperature, and additives on
the mode of the reaction (1,2- or 1,4-addition) has been
of major interest. Metalated amides and thioamides have
received little attention as nucleophiles; however, their
lithium derivatives frequently react with chalcones with
predominant 1,4-addition,8 while the corresponding ti-
tanium enolates favor 1,2-addition.9 The orientation of
additions to alkenones and alkyl 2-arylethenyl ketones
varies depending on the reaction conditions.7b,8 We know
of no reported reactions of amide-derived enolates with
cinnamaldehydes.
Resu lts a n d Discu ssion
Reactions of nonbranched aliphatic acylbenzotriazoles
1a ,b with chalcones follow the 1,4-addition pathway.
Thus, lithiated 1a (Scheme 1) with unsubstituted chal-
cone 4a (under the same conditions as those used by
Schick in his reaction with ketones) gave a mixture of
diastereomeric 3,4-dihydropyran-2-ones 6a and 7a in 70%
yield with the trans-isomer 6a predominating (with the
ratio of 4:1). A similar ratio of the diastereomers 6b/7b
was obtained in the analogous reaction with 4-chloro-
chalcone (Table 1). However, when 4-nitrochalcone was
used, the trans-isomer 6c was formed almost exclusively
(with the diastereoisomeric ratio of 20:1). Due to a
significant difference in the solubilities of 6c and 7c,
trans-isomer 6c was isolated pure by washing the dia-
stereomeric mixture with a small amount of diethyl ether.
A similar enhancement in the trans/cis isomeric ratio
was observed in the reactions with trans,trans-diben-
zylideneacetone (6e/7e, 12:1) and trans-dibenzoylethylene
(only trans-isomer 6d ). This tendency is explained by
additional stabilization of the intermediate enolate 5 with
In 1996, Schick et al.10 reported a fascinating formation
of di- and trisubstituted butyrolactones 3 by intramo-
(1) Hepworth, J . D.; Gabbutt, C. D.; Heron, B. M. In Comprehensive
Heterocyclic Chemistry-II; Katritzky, A. R., Rees, C. W., Scriven, E. F.
V., Eds.; Pergamon: Oxford, 1996; Vol. 5, p 351.
(2) Holliday, I. A.; Polgar, N. J . Chem. Soc. 1957, 2934.
(3) Santelli, M.; El Abed, D.; J ellal, A. J . Org. Chem. 1986, 51, 1199.
(4) Ito, Y.; Nakajo, E.; Sho, K.; Tamao, K. Tetrahedron Lett. 1987,
28, 2247.
(5) (a) Brady, W. T.; Watts, R. D. J . Org. Chem. 1981, 46, 4047. (b)
Mosti, L.; Schenone, P.; Menozzi, G.; Sancassan, F.; Baccichetti, F.;
Benetollo, F.; Bombieri, G. J . Heterocycl. Chem. 1988, 25, 407.
(6) (a) Hepworth, J . D. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984; Vol. 3, p
737. (b) Oare, D. A.; Heathcock, C. H. J . Org. Chem. 1990, 55, 157.
(7) (a) Yanovskaya, L. A.; Kryshtal’, G. V.; Kul’ganek, V. V. Russ.
Chem. Rev. 1984, 53, 1280. (b) Perlmutter, P. Conjugate Addition
Reactions in Organic Synthesis; Pergamon: Oxford, 1992.
(8) Goasdoue, C.; Goasdoue, N.; Gaudemar, M.; Mladenova, M. J .
Organomet. Chem. 1982, 226, 209.
(9) Goasdoue, C.; Goasdoue, N.; Gaudemar, M. Tetrahedron Lett.
1984, 25, 537.
(10) Wedler, C.; Kleiner, K.; Kunath, A.; Schick, H. Liebigs Ann.
1996, 881.
10.1021/jo011082s CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/06/2002

Addition of Acylbenzotriazoles to Aldehydes and Ketones
J . Org. Chem., Vol. 67, No. 9, 2002 3105
Sch em e 1
Sch em e 2
Ta ble 2. 1,3-Dien es 10 a n d 11
yield, (E,E):
entry compd
R1
R2
R3 R4
%
(E,Z)
1
2
3
4
5
6
7
8
9
10a /11a Et
10b/11b Et
10c/11c Et
Ph
H
H
H
H
H
H
H
Me
H
H
Me
H
68
50
66
25
82
66
48
58
8
62:38
71:29
52:48
a
42:58
58:42
a, b
2-MeOC6H4
2-furyl
4-t-BuC6H4 Me
Ta ble 1. 3,4,6-Tr isu bstitu ted 3,4-Dih yd r op yr a n -2-on es 6
a n d 7
10d
Et
10e/11e Et
Ph
n-C6H13 Ph
H
H
yield, trans:
entry compd
R1
R2
R3
%
cis
10f/11f
10g
n-C6H13 4-t-BuC6H4 Me
1
2
3
4
5
6
7
6a /7a Et
6b/7b Et
6c/7c Et
Ph
4-ClC6H4
4-O2NC6H4 Ph
PhCO
Ph
Ph
Ph
70
74
81
72
53
79
24
4:1
4:1
20:1
a
12:1
a
10h /11h n-C6H13 Ph
10i Me2CH Ph
H
H
55:45
a
a
b
Only (E,E). Ca. 5% of the (E,Z)-isomer 11g was observed in
6d
6e/7e Et
6f
6g/7g Me2CH Ph
Et
Ph
the 1H NMR spectrum.
PhCHdCH
Ph
Ph
n-C6H13 Ph
15:1
the proton abstraction, resulting in the formation of the
corresponding N,N-diisopropylamide. Replacement of
LDA with non-nucleophilic bases, such as n-butyllithium
or LiHMDS, did not lead to the formation of the expected
dihydropyranones. Switching to 1-(2-phenylethyl)carbo-
nylbenzotriazole (1f), which has an additional methylene
group, significantly suppressed the benzotriazolyl group
substitution with LDA, but led to a complex reaction
mixture with only traces of the desired product present.
Thus, the scope of this method for preparation of 3,4,6-
trisubstituted 3,4-dihydropyran-2-ones is essentially lim-
ited to the derivatives with non-R-branched alkyl sub-
stituents at the 3-position.
a
Only trans.
an electron-accepting R2 substituent, allowing for easier
C-C bond free rotation and the predominant formation
of the sterically favored trans-isomer. In each case, the
1
diastereomeric ratios were determined using H NMR
spectra of the crude reaction mixtures. These ratios were
later compared with those obtained after the column
chromatography purification: in all cases, no deviations
were observed.
Unexpectedly, lengthening the carbon chain in the
starting 1-acylbenzotriazole (R1 ) n-C6H13) also favors
the formation of the trans-isomer (compare entries 1 and
6 in Table 1). This and the predominant formation of the
trans-isomer (entry 7) from 1-isovalerylbenzotriazole (1c)
are ascribed to increased steric demands in the interme-
diate enolate 5. In the case of 1c, these steric demands
also lead to a significant decline in the product yield (see
Table 1). An attempt to carry out this reaction with even
more sterically hindered 1-neopentylcarbonylbenzotri-
azole (1d ) failed.
Lithiated acylbenzotriazoles were found to be unstable
at temperatures above -60 °C and, thus, react in the
temperature range -60 to -78 °C. This suggests that
the product ratios are the kinetic ones. Despite the use
of excess acylbenzotriazole, minor amounts of the starting
R,â-unsaturated carbonyl compounds were still present
in the reaction mixtures, indicating that the acylbenzo-
triazole decomposition process competes with the desired
cycloaddition reaction. Kinetic control could also explain
the lack of reactivity of sterically hindered 1-alkylcarbo-
nylbenzotriazoles.
In contrast to the foregoing results, treatment of
lithiated 1-acylbenzotriazoles with cinnamaldehydes re-
sults in 1,2-addition and subsequent formation of conju-
gated dienes. Thus, reaction of n-butyrylbenzotriazole 1a
with LDA and then with trans-cinnamaldehyde 8a under
the standard reaction conditions afforded a mixture of
(E,E) (10a ) and (E,Z) (11a ) dienes with the E,E-isomer
predominating (Scheme 2, Table 2). o-Methoxycinnam-
aldehyde 8b and 3-(2-furyl)acrolein 8c gave the corre-
sponding dienes 10b/11b and 10c/11c. As shown in Table
2, an introduction of an electron-donating substituent
into the aromatic ring increases the relative amount of
the E,E-isomer 10, while with the electron-accepting
2-furyl group an almost equimolar mixture of the isomers
was formed. An introduction of a methyl group at the
R-position of the starting cinnamaldehyde leads to a
general decrease in the product yield; however, the
increased steric demands favor the formation of a trans
double bond (see entries 4 and 7, Table 2). Interestingly,
the diene 10g was obtained reproducibly in double the
yield of the homologous diene 10d . Also, the diene 10g
was contaminated with a minor amount (less than 5%)
of the isomeric 11g, although, from the standpoint of
steric hindrance, the opposite results were expected.
The behavior of aryl-substituted acylbenzotriazoles in
the reaction with chalcones has also been investigated.
Under the standard reaction conditions, 1-benzylcarbo-
nylbenzotriazole (1e) is more prone to nucleophilic sub-
stitution of the benzotriazolyl group with LDA than to

3106 J . Org. Chem., Vol. 67, No. 9, 2002
Katritzky and Denisko
(t, J ) 7.3 Hz, 1H), 7.65 (t, J ) 7.3 Hz, 1H), 8.12 (d, J ) 8.2
Hz, 1H), 8.30 (d, J ) 8.2 Hz, 1H); 13C NMR δ 13.7, 17.9, 37.3,
114.4, 120.1, 126.0, 130.3, 131.1, 146.1, 172.5.
The suggested pathway of this reaction is shown in
Scheme 2. In contrast to reactions with chalcones,
reactions of lithiated 1-acylbenzotriazoles with cinnam-
aldehydes follow exclusively the 1,2-addition pathway.
Although examples of subsequent isomerization of kinetic
1,2-adducts to thermodynamic 1,4-adducts are well-
known, in our case the formation of the latter was not
observed, probably due to further transformations of 1,2-
adducts at low temperatures. Analogous 1,2-adducts of
type 9 were previously reported as intermediates in the
reaction of acyl chloride derived ketenes with carbonyl
compounds;11 they were also shown to undergo thermal
decarboxylation with the formation of the corresponding
olefins. Our attempts to avoid CO2 elimination and to
isolate the intermediates 9 by quenching the reaction at
low temperature were unsuccessful: only dienes 10/11
were obtained. This phenomenon is probably explained
by preferential formation of a highly conjugated aryldiene
system (R2 is an aryl (heteroaryl) group in all cases).
Interestingly, 2-phenylethenyl methyl ketone (8e, R2
) Ph, R3 ) H, R4 ) Me) tends to react exclusively by the
1,2-addition route, similarly to the aldehydes discussed
above, but not to chalcones. Thus, the reactions of
acylbenzotriazoles 1a ,b with 8e gave almost equimolar
mixtures of (E,E) and (E,Z) dienes 10e/11e and 10h /11h ,
respectively.
1-(n -Octa n oyl)ben zotr ia zole (1b): colorless oil10 (96%); 1H
NMR δ 0.89 (t, J ) 6.6 Hz, 3H), 1.30-1.51 (m, 8H), 1.86-1.94
(m, 2H), 3.42 (t, J ) 7.5 Hz, 2H), 7.50 (t, J ) 7.4 Hz, 1H), 7.65
(t, J ) 7.4 Hz, 1H), 8.12 (d, J ) 8.2 Hz, 1H), 8.29 (d, J ) 8.2
Hz, 1H); 13C NMR δ 14.0, 22.5, 24.4, 28.9, 29.0, 31.6, 35.5,
114.4, 120.0, 126.0, 130.2, 131.1, 146.1, 172.6.
1-(Ben zotr ia zol-1-yl)-3-m eth ylbu ta n -1-on e (1c): color-
1
less liquid (96%); H NMR δ 1.11 (d, J ) 6.7 Hz, 6H), 2.40-
2.50 (m, 1H), 3.31 (d, J ) 7.0 Hz, 2H), 7.50 (dd, J ) 8.1, 7.3
Hz, 1H), 7.65 (dd, J ) 8.0, 7.3 Hz, 1H), 8.11 (d, J ) 8.2 Hz,
1H), 8.30 (d, J ) 8.2 Hz, 1H); 13C NMR δ 22.5, 25.5, 44.0, 114.4,
120.0, 126.0, 130.2, 131.0, 146.1, 171.9. Anal. Calcd for
C
11H13N3O: C, 65.01; H, 6.45; N, 20.67. Found: C, 65.32; H,
6.65; N, 21.00.
1-(Ben zotr iazol-1-yl)-3,3-dim eth ylbu tan -1-on e (1d): white
plates (70%), mp 56-57 °C (from hexanes) (lit.14 56-57 °C);
1H NMR δ 1.17 (s, 9H), 3.36 (s, 2H), 7.51 (t, J ) 7.7 Hz, 1H),
7.66 (t, J ) 7.7 Hz, 1H), 8.12 (d, J ) 8.2 Hz, 1H), 8.34 (d, J )
8.2 Hz, 1H); 13C NMR δ 29.8, 32.0, 47.1, 114.6, 120.1, 126.1,
130.2, 131.1, 146.2, 171.4.
1-(Ben zotr ia zol-1-yl)-2-p h en yleth a n on e (1e): white mi-
crocrystals (67%), mp 67-68 °C (from hexanes) (lit.15 70-71
°C); 1H NMR δ 4.73 (s, 2H), 7.30-7.40 (m, 3H), 7.45-7.52 (m,
3H), 7.63 (t, J ) 7.3 Hz, 1H), 8.12 (d, J ) 8.2 Hz, 1H), 8.26 (d,
J ) 8.2 Hz, 1H); 13C NMR δ 42.0, 114.4, 120.1, 126.2, 127.6,
128.8, 129.8, 130.5, 131.2, 132.5, 146.3, 170.2.
1-(Ben zotr ia zol-1-yl)-3-p h en ylp r op a n -1-on e (1f): white
microcrystals (98%), mp 61-62 °C (from hexanes) (lit.10 62-
63 °C); 1H NMR δ 3.24 (t, J ) 7.7 Hz, 2H), 3.77 (t, J ) 7.7 Hz,
2H), 7.18-7.28 (m, 1H), 7.30-7.35 (m, 4H), 7.50 (pseudo-t, J
) 7.6 Hz, 1H), 7.65 (pseudo-t, J ) 7.7 Hz, 1H), 8.12 (d, J )
8.2 Hz, 1H), 8.29 (d, J ) 8.2 Hz, 1H); 13C NMR δ 30.2, 37.1,
114.4, 120.1, 126.1, 126.5, 128.4, 128.6, 130.4, 131.0, 139.8,
146.1, 171.6.
Reactions of lithiated 1-acylbenzotriazoles with cinna-
maldehydes and styryl methyl ketone generally afford
1,3-dienes in moderate yields and, except in the cases of
sterically hindered substrates, as mixtures of trans and
cis isomers. Thus, this methodology provides no advan-
tages compared to established methods for the prepara-
tion of 1,3-dienes.12
Gen er a l P r oced u r e for th e Syn th esis of 3,4,6-Tr isu b-
stitu ted 3,4-Dih yd r op yr a n -2-on es 6/7 a n d 1,3-Dien es 10/
11. A solution of di(isopropyl)amine (0.6 mL, 4.0 mmol) in dry
THF (40 mL) was cooled to -10 °C under nitrogen, and 1.58
N n-BuLi in hexanes (2.2 mL, 3.5 mmol) was added dropwise.
The colorless solution obtained was allowed to warm up to
room temperature during 40 min, and then it was cooled to
-78 °C. A solution of 1-acylbenzotriazole (3.5 mmol) in dry
THF (20 mL) was added slowly dropwise. The reaction mixture
was stirred at -78 °C for 20 min, and then a solution of the
R,â-unsaturated aldehyde or ketone (3.0 mmol) in THF (20 mL)
was added slowly. The reaction mixture was allowed to warm
up to room temperature during 3.5 h, and it was stirred at
room temperature for an additional 1 h. Then it was quenched
with aqueous saturated NH4Cl and extracted with ether. The
organic fraction was washed with water and brine and dried
over MgSO4. After solvent removal, the residue was purified
by column chromatography (SiO2; dichloromethane:hexanes )
1:3 to 1:1 (for 3,4-dihydropyran-2-ones) or ethyl acetate:
hexanes ) 1:10 (for 1,3-dienes)).
Con clu sion s
Lithiated aliphatic nonbranched 1-acylbenzotriazoles
undergo 1,4-addition to R,â-unsaturated aromatic ketones
to afford previously unknown 3-alkyl-4,6-diaryl-3,4-di-
hydropyran-2-ones, predominantly (or exclusively) as
trans-isomers, in good yields. An analogous reaction with
cinnamaldehydes or with methyl styryl ketone follows
the 1,2-addition pathway resulting in formation of vari-
ous 1,3-dienes. Introduction of a â-substituent into the
alkyl chain of the acylbenzotriazole leads to a significant
decrease in the product yield, although an improvement
in the stereoselectivity is observed.
Exp er im en ta l Section
Gen er a l Com m en ts. Melting points were measured on a
Mel-Temp apparatus and are uncorrected. 1H and 13C NMR
data were recorded on Gemini 300 MHz NMR spectrometer
(300 and 75 MHz, respectively) in CDCl3 as a solvent and with
TMS as an internal standard. For isomeric mixtures, signals
common for both isomers are provided without additional
specification. Column chromatography was carried out on silica
gel (activated, neutral, 50-200 micron). Tetrahydrofuran was
distilled from sodium/benzophenone immediately prior to use.
Di(isopropyl)amine was distilled from sodium and handled
under nitrogen. 1-Acylbenzotriazoles were prepared following
the known procedure.13
3-E t h yl-4,6-d ip h en yl-3,4-d ih yd r op yr a n -2-on e (6a /7a ):
1
colorless oil (70%); H NMR δ 0.88-1.07 (m, 3H), 1.19-1.29
(m, 1H), 1.59-1.81 (m, 1H), 2.73 (dd, J ) 12.6, 7.1 Hz, 1H
(cis)), 2.84 (dd, J ) 14.0, 6.9 Hz, 1H (trans)), 3.71 (dd, J ) 7.1,
4.6 Hz, 1H (cis)), 3.84 (pseudo-t, J ) 6.6 Hz, 1H (trans)), 5.84
(d, J ) 4.5 Hz, 1H (cis)), 6.06 (d, J ) 6.5 Hz, 1H (trans)), 7.15-
7.20 (m, 2H), 7.21-7.42 (m, 6H), 7.65-7.69 (m, 2H); 13C NMR
δ 11.3 (cis) and 12.0 (trans), 19.8 (trans) and 22.7 (cis), 41.2
(trans) and 42.4 (cis), 45.9 (trans) and 47.9 (cis), 103.6 (cis)
and 104.7 (trans), 124.6, 127.4, 127.6, 128.1, 128.5, 128.8,
129.1, 132.2, 138.0, 141.5, 149.4, 150.1, 170.4. HRMS (FAB)
calcd for C19H19O2 (M + 1): 279.1385. Found: 279.1401.
1-Bu tyr ylben zotr ia zole (1a ): white plates (95%), mp 56-
57 °C (from hexanes) (lit.10 54-55 °C); 1H NMR δ 1.12 (t, J )
7.4 Hz, 3H), 1.91-2.00 (m, 2H), 3.41 (t, J ) 7.4 Hz, 2H), 7.50
(13) Katritzky, A. R.; Pastor, A.; Voronkov, M. V. J . Heterocycl.
Chem. 1999, 36, 777.
(11) Arrastia, I.; Cossio, F. P. Tetrahedron Lett. 1996, 37, 7143.
(12) White, J . D.; J ensen, M. S. Tetrahedron 1995, 51, 5743 and
references cited therein.
(14) Katritzky, A. R.; Pastor, A. J . Org. Chem. 2000, 65, 3679.
(15) Parshad, R.; Sharma, K. S. J . Indian Chem. Soc. 1990, 67, 150;
Chem. Abstr. 1990, 113, 68144g.

Addition of Acylbenzotriazoles to Aldehydes and Ketones
J . Org. Chem., Vol. 67, No. 9, 2002 3107
3-Eth yl-4-(4-ch lor oph en yl)-6-p h en yl-3,4-d ih ydr opyr a n -
2-on e (6b/7b): colorless oil (74%); H NMR δ 1.00 (t, J ) 7.3
5.84 (dt, J ) 15.1, 6.6 Hz, 1H (E,E)), 6.06-6.25 (m, 1H), 6.42
(d, J ) 15.8 Hz, 1H (E,E)), 6.50 (d, J ) 15.5 Hz, 1H (E,Z)),
6.74 (dd, J ) 15.6, 10.3 Hz, 1H (E,E)), 7.06 (dd, J ) 15.5, 11.1
Hz, 1H (E,Z)), 7.17 (dd, J ) 13.5, 7.0 Hz, 1H), 7.24-7.41 (m,
4H); 13C NMR δ 13.5 and 14.3, 21.3 and 25.8, 124.3, 126.1,
126.3, 127.0, 127.3, 128.1, 128.5, 128.6, 129.4, 129.5, 129.9,
131.9, 134.8, 137.3, 137.6, 137.7.
1
Hz, 3H), 1.12-1.28 (m, 1H), 1.63-1.82 (m, 1H), 2.67 (dd, J )
12.6, 7.0 Hz, 1H (cis)), 2.81 (dd, J ) 13.9, 7.0 Hz, 1H (trans)),
3.67 (dd, J ) 7.0, 4.6 Hz, 1H (cis)), 3.79 (t, J ) 6.6 Hz, 1H
(trans)), 5.78 (d, J ) 4.5 Hz, 1H (cis)), 6.01 (d, J ) 6.5 Hz, 1H
(trans)), 7.08 (d, J ) 8.4 Hz, 2H (trans)), 7.14 (d, J ) 8.4 Hz,
2H (cis)), 7.24 (d, J ) 8.5 Hz, 2H (trans)), 7.29 (d, J ) 8.4 Hz,
2H (cis)), 7.30-7.41 (m, 3H), 7.64-7.68 (m, 2H); 13C NMR δ
11.2 (cis) and 11.9 (trans), 19.7 (trans) and 22.6 (cis), 40.5
(trans) and 41.7 (cis), 45.6 (trans) and 47.8 (cis), 102.8 (cis)
and 104.1 (trans), 124.5, 128.5, 128.7, 128.9, 129.1, 129.2,
129.3, 131.8 (cis) and 131.9 (trans), 133.1 (cis) and 133.3
(trans), 136.4, 139.9, 149.7 (cis) and 150.3 (trans), 169.4 (cis)
and 169.9 (trans). HRMS (FAB) calcd for C19H18ClO2 (M + 1):
313.0995. Found: 313.0975.
1-(2-Meth oxyp h en yl)h exa -1,3-d ien e (10b/11b): colorless
1
oil (50%); H NMR δ 1.04 (t, J ) 7.5 Hz, 3H), 2.11-2.21 (m,
2H (E,E)), 2.27-2.33 (m, 2H (E,Z)), 3.83 (s, 3H), 5.49 (dt, J )
10.4, 7.6 Hz, 1H (E,Z)), 5.84 (dt, J ) 15.1, 6.6 Hz, 1H (E,E)),
6.12-6.28 (m, 1H), 6.76-6.95 (m, 3H + H (E,E)), 7.08 (dd, J
) 15.8, 11.1 Hz, 1H (E,Z)), 7.14-7.24 (m, 1H), 7.44 (d, J ) 7.7
Hz, 1H (E,E)), 7.49 (d, J ) 7.7 Hz, 1H (E,Z)); 13C NMR δ 13.5
(E,E) and 14.3 (E,Z), 21.3 (E,Z) and 25.8 (E,E), 55.4, 110.8,
120.6, 124.7, 125.0, 126.2, 126.4, 126.6, 126.7, 128.0, 128.3,
128.8, 130.1, 130.3, 134.2, 136.7, 156.5. Anal. Calcd for
tr a n s-3-Eth yl-4-(4-n itr op h en yl)-6-p h en yl-3,4-d ih yd r o-
p yr a n -2-on e (6c): pale-yellow needles (81%), mp 98-99 °C
C
13H16O: C, 82.93; H, 8.57. Found: C, 83.19; H, 8.84.
1
1-(2-F u r yl)h exa -1,3-d ien e (10c/11c): yellow unstable liq-
(from ethyl ether); H NMR δ 1.05 (t, J ) 7.3 Hz, 3H), 1.16-
1
uid (66%); H NMR δ 1.03 (t, J ) 7.4 Hz, 3H), 2.10-2.20 (m,
2H (E,E)), 2.24-2.34 (m, 2H (E,Z)), 5.51 (dt, J ) 10.4, 7.7 Hz,
1H (E,Z)), 5.85 (dt, J ) 15.1, 6.6 Hz, 1H (E,E)), 6.01-6.14 (m,
1H), 6.17-6.28 (m, 2H), 6.33-6.38 (m, 1H), 6.67 (dd, J ) 15.6,
10.6 Hz, 1H (E,E)), 6.97 (dd, J ) 15.4, 11.5 Hz, 1H (E,Z)), 7.33
(d, J ) 6.6 Hz, 1H); 13C NMR δ 13.5 and 14.3, 21.3 and 25.9,
107.3, 108.0, 111.4, 111.5, 117.8, 119.5, 123.1, 127.7, 128.2,
129.1, 135.1, 137.6, 141.6, 141.9, 153.5. HRMS (FAB) calcd
for C10H13O (M + 1): 149.0966. Found: 149.1064.
(E,E)-1-(4-ter t-Bu t ylp h en yl)-2-m et h ylh exa -1,3-d ien e
(10d ): colorless oil (25%); 1H NMR δ 1.05 (t, J ) 7.4 Hz, 3H),
1.32 (s, 3H), 1.99 (s, 2H), 2.10-2.22 (m, 2H), 5.80 (dt, J ) 15.7,
6.5 Hz, 1H), 6.23 (d, J ) 15.5 Hz, 1H), 6.40 (s, 1H), 7.22 (d, J
) 8.0 Hz, 2H), 7.34 (d, J ) 8.0 Hz, 2H); 13C NMR δ 13.9, 14.0,
26.0, 31.3, 34.5, 125.0, 128.9, 129.1, 131.5, 134.4, 135.3, 149.1.
Anal. Calcd for C17H24: C, 89.40; H, 10.61. Found: C, 89.75;
H, 11.02.
1.26 (m, 1H), 1.73-1.84 (m, 1H), 2.93 (q, J ) 7.0 Hz, 1H), 3.98
(t, J ) 6.6 Hz, 1H), 6.04 (d, J ) 6.3 Hz, 1H), 7.35 (d, J ) 8.7
Hz, 2H), 7.40-7.42 (m, 3H), 7.66-7.70 (m, 2H), 8.18 (d, J )
8.7 Hz, 2H); 13C NMR δ 12.0, 19.9, 41.1, 45.5, 103.1, 124.0,
124.7, 128.6, 129.0, 129.5, 131.7, 145.7, 147.4. 151.1, 169.5.
Anal. Calcd for C19H17NO4: C, 70.58; H, 5.30; N, 4.33. Found:
C, 70.25; H, 5.64; N, 4.31.
tr a n s-3-Eth yl-4-ben zoyl-6-p h en yl-3,4-d ih yd r op yr a n -2-
on e (6d ): pale-yellow microcrystals (72%), mp 74-76 °C (from
1
hexanes); H NMR δ 0.99 (t, J ) 7.4 Hz, 3H), 1.51-1.64 (m,
1H), 1.77-1.87 (m, 1H), 2.71 (ddd, J ) 8.5, 5.9, 2.6 Hz, 1H),
3.63 (t, J ) 2.6 Hz, 1H), 5.46 (d, J ) 2.5 Hz, 1H), 7.35-7.44
(m, 6H), 7.52-7.56 (m, 2H), 7.61-7.65 (m, 2H); 13C NMR δ
12.0, 25.4, 49.2, 56.4, 98.3, 115.3, 125.1, 125.6, 128.5, 128.7,
129.0, 129.3, 129.4, 139.2, 155.4, 177.2. HRMS (EI) calcd for
C
20H18O3 (M): 306.1256. Found: 306.1257.
3-Eth yl-4-p h en yl-6-(tr a n s-2-styr yl)-3,4-d ih yd r op yr a n -
1
1-P h en yl-3-m eth ylh exa -1,3-d ien e (10e/11e): colorless liq-
2-on e (6e/7e): colorless oil (53%); H NMR δ 1.00 (t, J ) 7.4
Hz, 3H), 1.16-1.26 (m, 1H), 1.69-1.80 (m, 1H), 2.70 (dd, J )
12.8, 6.8 Hz, 1H (cis)), 2.80 (dd, J ) 13.9, 6.9 Hz, 1H (trans)),
3.65 (dd, J ) 6.9, 4.7 Hz, 1H (cis)), 3.78 (t, J ) 6.7 Hz, 1H
(trans)), 5.38 (d, J ) 4.7 Hz, 1H (cis)), 5.59 (d, J ) 6.3 Hz, 1H
(trans)), 6.52 (d, J ) 15.9 Hz, 1H), 7.08-7.14 (m, 3H), 7.18-
7.36 (m, 6H), 7.44 (d, J ) 7.6 Hz, 2H); 13C NMR δ (only for
the trans-isomer) 12.0, 19.8, 41.4, 46.0, 109.3, 119.9, 126.8,
127.6, 128.0, 128.2, 128.7, 128.8, 129.9, 136.1, 138.0, 149.4,
170.2. HRMS (FAB) calcd for C21H21O2 (M + 1): 305.1542.
Found: 305.1502.
1
uid17 (82%); H NMR δ 1.02 (t, J ) 7.6 Hz, 3H (E,E)), 1.03 (t,
J ) 7.6 Hz, 3H (E,Z)), 1.84 (s, 3H (E,E)), 1.92 (s, 3H (E,Z)),
2.12-2.36 (m, 2H), 5.45 (t, J ) 7.4 Hz, 1H (E,Z)), 5.62 (t, J )
7.3 Hz, 1H (E,E)), 6.44 (d, J ) 16.1 Hz, 1H (E,E)), 6.54 (d, J )
16.1 Hz, 1H (E,Z)), 6.79 (d, J ) 16.1 Hz, 1H (E,E)), 7.12-7.24
(m, 1H + 1H (E,Z)), 7.25-7.34 (m, 2H), 7.36-7.46 (m, 2H);
13C NMR δ 12.2, 14.0, 14.5, 20.5, 20.9, 21.7, 125.5, 126.0, 126.1,
126.3, 126.8, 127.1, 128.1, 128.5, 128.6, 131.4, 133.2, 133.9,
134.0, 135.9, 138.0.
1-P h en yld eca -1,3-d ien e (10f/11f): colorless liquid18 (66%);
1H NMR δ 0.89 (t, J ) 6.9 Hz, 3H), 1.29-1.42 (m, 8H), 2.14
(dd, J ) 14.0, 6.9 Hz, 2H (E,E)), 2.28 (dd, J ) 14.0, 6.9 Hz, 2H
(E,Z)), 5.53 (dt, J ) 10.7, 7.7 Hz, 1H (E,Z)), 5.82 (dt, J ) 15.0,
7.0 Hz, 1H (E,E)), 6.11-6.25 (m, 1H), 6.43 (d, J ) 15.7 Hz, 1H
(E,E)), 6.52 (d, J ) 15.7 Hz, 1H (E,Z)), 6.75 (dd, J ) 15.7, 10.3
Hz, 1H (E,E)), 7.06 (dd, J ) 15.5, 11.1 Hz, 1H (E,Z)), 7.15-
7.43 (m, 5H); 13C NMR δ 14.1, 22.6, 28.0, 28.9 and 29.0, 29.3
and 29.7, 31.7 and 32.9, 124.5, 126.1 and 126.3, 127.0 and
127.3, 128.5 and 128.6, 128.7 and 129.5, 129.9 and 130.4, 131.9
and 133.4, 136.1 and 137.7.
t r a n s-3-(n -H e xyl)-4,6-d ip h e n yl-3,4-d ih yd r op yr a n -2-
on e (6f): white needles (79%), mp 81-82 °C (from hexanes);
1H NMR δ 0.86 (t, J ) 6.6 Hz, 3H), 1.15-1.38 (m, 7H), 1.39-
1.44 (m, 2H), 1.66-1.77 (m, 1H), 2.93 (dd, J ) 13.7, 7.0 Hz,
1H), 3.83 (pseudo-t, J ) 6.4 Hz, 1H), 6.07 (d, J ) 6.4 Hz, 1H),
7.15-7.18 (m, 2H), 7.23-7.43 (m, 6H), 7.66-7.70 (m, 2H); 13
C
NMR δ 14.0, 22.5, 26.4, 27.2, 29.1, 31.6, 41.5, 44.2, 104.8, 124.6,
127.6, 128.1, 128.5, 128.9, 129.1, 132.2, 138.0, 150.1, 170.6.
Anal. Calcd for C23H26O2: C, 82.60; H, 7.84. Found: C, 82.88;
H, 8.15.
(E,E)-1-(4-ter t-Bu t ylp h en yl)-2-m et h yld eca -1,3-d ien e
3-I s o p r o p y l-4,6-d ip h e n y l-3,4-d ih y d r o p y r a n -2-o n e
(6g/7g): white microcrystals (24%), mp 74-77 °C (from hex-
anes); 1H NMR δ 0.90 (d, J ) 6.7 Hz, 3H), 0.94 (d, J ) 6.5 Hz,
3H), 1.84-1.92 (m, 1H), 2.55 (dd, J ) 8.0, 3.4 Hz, 1H (cis)),
2.67 (dd, J ) 8.6, 6.8 Hz, 1H (trans)), 3.79 (dd, J ) 5.7, 3.3
Hz, 1H (cis)), 3.89 (pseudo-t, J ) 6.6 Hz, 1H (trans)), 5.84 (d,
J ) 5.9 Hz, 1H (cis)), 6.01 (d, J ) 6.6 Hz, 1H (trans)), 7.20-
7.38 (m, 8H), 7.61-7.65 (m, 2H); 13C NMR δ 20.6, 21.8, 25.9,
40.6, 50.5, 105.4, 124.5, 127.4, 127.9, 128.4, 128.8, 128.9, 132.1,
138.7, 149.5, 169.8. HRMS (EI)calcd for C20H20O2 (M): 292.1463.
Found: 292.1429.
1
(10g): colorless liquid (49%); H NMR δ 0.89 (t, J ) 6.6 Hz,
3H), 1.32 (s, 9H), 1.30-1.51 (m, 8H), 1.99 (s, 3H), 2.11-2.19
(m, 2H), 5.76 (dt, J ) 15.5, 6.9 Hz, 1H), 6.23 (d, J ) 15.5 Hz,
1H), 6.39 (s, 1H), 7.22 (d, J ) 8.4 Hz, 2H), 7.35 (d, J ) 8.4 Hz,
2H); 13C NMR δ 14.0, 14.1, 22.6, 29.0, 29.6, 31.3, 31.8, 33.0,
34.5, 125.0, 128.9, 129.0, 130.1, 135.2, 135.3, 135.4, 149.1.
Anal. Calcd for C21H32: C, 88.65; H, 11.36. Found: C, 88.73;
H, 11.67.
1-P h en yl-3-m eth yld eca -1,3-d ien e (10h /11h ): colorless
1
liquid (58%); H NMR δ 0.89 (t, J ) 6.6 Hz, 3H), 1.29-1.43
(m, 8H), 1.86 (s, 3H (E,E)), 1.94 (s, 3H (E,Z)), 2.14-2.30 (m,
2H), 5.47 (t, J ) 7.4 Hz, 1H (E,Z)), 5.64 (t, J ) 7.4 Hz, 1H
1-P h en ylh exa-1,3-dien e (10a/11a): colorless liquid16 (68%);
1H NMR δ 1.03 (t, J ) 7.5 Hz, 3H), 2.10-2.20 (m, 2H (E,E)),
2.22-2.36 (m, 2H (E,Z)), 5.51 (dt, J ) 10.6, 7.6 Hz, 1H (E,Z)),
(17) Miravalles, R.; Guillarmod, A. J . Helv. Chim. Acta 1966, 49,
2313.
(16) Baudin, J . B.; Hareau, G.; J ulia, S. A.; Lorne, R.; Ruel, O. Bull.
Soc. Chim. Fr. 1993, 130, 856.
(18) Murakami, M.; Ubukata, M.; Ito, Y. Tetrahedron Lett. 1998,
39, 7361.

3108 J . Org. Chem., Vol. 67, No. 9, 2002
Katritzky and Denisko
(E,E)), 6.44 (d, J ) 16.0 Hz, 1H (E,E)), 6.54 (d, J ) 16.1 Hz,
1H (E,Z)), 6.81 (d, J ) 16.1 Hz, 1H (E,E)), 7.15-7.24 (m, 1H
+ 1H (E,Z)), 7.27-7.35 (m, 2H), 7.38-7.45 (m, 2H); 13C NMR
δ 12.4, 14.1, 20.5, 22.6 (E,Z), 27.6 and 28.5, 29.0 and 29.1, 29.6
and 29.9, 31.8 (E,E), 125.4, 126.1, 126.3, 126.8, 127.1, 128.0,
128.5 and 128.6, 131.8, 132.5, 133.6, 134.1, 134.6, 138.0 and
138.1. HRMS (FAB) calcd for C17H24 (M): 228.1878. Found:
228.1853.
5.81 (dd, J ) 15.2, 6.7 Hz, 1H), 6.17 (dd, J ) 15.1, 10.3 Hz,
1H), 6.46 (d, J ) 15.8 Hz, 1H), 6.75 (dd, J ) 15.7, 10.3 Hz,
1H), 7.19 (t, J ) 7.1 Hz, 1H), 7.26-7.32 (m, 2H), 7.37 (d, J )
7.4 Hz, 2H); 13C NMR δ 22.3, 31.3, 126.1, 127.0, 127.5, 128.5,
129.6, 130.1, 137.7, 142.7.
J O011082S
1-P h en yl-5-m eth ylh exa -1,3-d ien e (10i): colorless liquid19
(19) Katritzky, A. R.; Cheng, D.; Henderson, S. A.; Li, J . J . Org.
Chem. 1998, 63, 6704.
1
(8%); H NMR δ 1.05 (d, J ) 6.7 Hz, 6H), 2.36-2.44 (m, 1H),