Titanocene(III) chloride mediated radical-induced addition to Baylis-Hillman adducts: Synthesis of (E)- and (Z)-trisubstituted alkenes and α-methylene/arylidene δ-lactones

Article abstract of DOI:10.1021/jo800049p

(Chemical Equation Presented) Baylis-Hillman adduct underwent smooth radical-induced condensation with activated bromo compounds and epoxides using titanocene(III) chloride (Cp₂TiCl) as the radical generator. The reactions of activated bromo co

Full text of DOI:10.1021/jo800049p

Titanocene(III) Chloride Mediated Radical-Induced Addition to
Baylis-Hillman Adducts: Synthesis of (E)- and (Z)-Trisubstituted
Alkenes and r-Methylene/Arylidene δ-Lactones
Samir K. Mandal, Moumita Paira, and Subhas C. Roy*
Department of Organic Chemistry, Indian Association for the CultiVation of Science, JadaVpur,
Kolkata 700 032, India
ocscr@iacs.res.in
ReceiVed January 9, 2008
Baylis-Hillman adduct underwent smooth radical-induced condensation with activated bromo compounds
and epoxides using titanocene(III) chloride (Cp2TiCl) as the radical generator. The reactions of activated
bromo compounds with 3-acetoxy-2-methylene alkanoates provided (E)-alkenes exclusively, whereas
similar reactions with 3-acetoxy-2-methylenealkanenitriles led to (Z)-alkenes as the major product. The
reactions of epoxides with Baylis-Hillman adduct furnished R-methylene/arylidene-δ-lactones in good
yield via addition followed by in situ lactonization.
Acetates of Baylis-Hillman adduct have been established
for stereoselective synthesis of different multifunctional mol-
ecules.1 Moreover, the substituted alkene moiety is a part of
varieties of naturally occurring bioactive molecules along with
several important pheromones and antibiotics and also the key
intermediate in the stereospecific synthesis of important com-
pounds.2 Various R-substituted acrylate esters have been
extensively used in the synthesis of pseodopeptides, including
inhibitors of metalloproteases and ATP-dependent ligases based
on the 1,4-addition reaction.3 Several methods are reported in
the literature for the synthesis of substituted alkenes from
Baylis-Hillman adducts such as Pd-catalyzed cross-coupling
reaction,4 reaction with Grignard reagent,5 Friedel-Crafts
reaction,6 and more recently reaction of trialkylindium reagent.7
Earlier, Das et al. have a considerable amount of contribution
in the synthesis of alkenes from Baylis-Hillman adducts.8 They
have also developed a very elegant and high-yielding similar
transformation using Zn in aqueous medium where both
(4) (a) Kabalka, G. W.; Venkataiah, B.; Dong, G. Org. Lett. 2003, 5, 3803.
(b) Kabalka, G. W.; Dong, G.; Venkataiah, B.; Chen, C. J. Org. Chem. 2005,
70, 9207.
(5) Basavaiah, D.; Sarma, P. K. S.; Bhavani, A. K. D. J. Chem. Soc.,
Chem.Commun. 1994, 1091.
(1) (a) Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. Engl. 1985,
24, 94. (b) Basavaiah, D.; Bakthadoss, M.; Pandiaraju, S. Chem. Commun. 1998,
1639. (c) Silveira, G. P. de C.; Coelho, F. Tetrahedron Lett. 2005, 46, 6477.
(2) (a) Bradshaw, J. W. S.; Baker, R.; Howse, P. E. Nature 1975, 258, 230.
(b) Rossi, R.; Carpita, A.; Messari, T. Synth. Commun. 1992, 22, 603. (c) Marfort,
A.; McGuirk, P. R.; Helquist, P. J. Org. Chem. 1979, 44, 3888.
(6) (a) Basavaiah, D.; Pandiaraju, S.; Padmaja, K. Synlett 1996, 393. (b)
Basavaiah, D.; Krishnamacharyulu, M.; Hyma, R. S.; Pandiaraju, S. Tetrahedron
Lett. 1997, 38, 2141.
(7) Ranu, B. C.; Chattopadhyay, K.; Jana, R. Tetrahedron Lett. 2007, 48,
3847.
(3) (a) Jackson, P. F.; Cole, D. C.; Slusher, B. S.; Stetz, S. L.; Ross, L. E.;
Donzanti, B. A.; Trainor, D. A. J. Med. Chem. 1996, 39, 619. (b) Vassiliou, S.;
Mucha, A.; Cuniasse, P.; Georgiadis, D.; Lucet-Levannier, K.; Beau, F.; Kannan,
R.; Murphy, G.; Kna¨uper, V.; Rio, M. C.; Basset, P.; Yiotakis, A.; Dive, V.
J. Med. Chem. 1999, 42, 2610. (c) Valiaeva, N.; Bartley, D.; Konno, T.; Coward,
J. K. J. Org. Chem. 2001, 66, 5146. (d) Hin, B.; Majer, P.; Tsukamoto, T. J.
Org. Chem. 2002, 67, 7365.
(8) (a) Das, B.; Banerjee, J.; Chowdhury, N.; Majhi, A.; Holla, H. Synlett
2006, 1879. (b) Das, B.; Venkateswarlu, K.; Krishnah, M.; Holla, H.; Majhi, A.
HelV. Chim. Acta 2006, 89, 1417. (c) Das, B.; Chowdhury, N.; Banerjee, J.;
Majhi, A.; Mahender, G. Chem. Lett. 2006, 35, 358. (d) Das, B.; Chowdhury,
N.; Damodar, K.; Banerjee, J. Chem. Pharm. Bull. 2007, 55, 1274. (e) Das, B.;
Holla, H.; Srinivas, Y.; Chowdhury, N.; Bandgar, B. P. Tetrahedron Lett. 2007,
48, 3201.
10.1021/jo800049p CCC: $40.75
Published on Web 04/22/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 3823–3827 3823

Mandal et al.
SCHEME 3. Ti(III)-Mediated Addition of Epoxides to
SCHEME 1. Ti(III)-Mediated Addition of Activated Bromo
Compounds to Baylis-Hillman Adduct
Baylis-Hillman Adduct
SCHEME 2. Ti(III)-Mediated Addition of Activated Bromo
Compounds to Alkenoates and Alkenenitriles
an E/Z mixture with Z-2-substituted 2-alkenenitrile as the major
product (Scheme 2).
A series of Baylis-Hillman adducts were subjected to
titanocene(III) chloride mediated reaction with various activated
bromo compounds, and the results are summarized in Table 1.
Activated iodo compounds also underwent similar reactions to
furnish E-2-substituted 2-alkenoates (entries 12, 13, 15, 17, and
18, Table 1). But, nonactivated iodo compound (entry 20, Table
1) or an electron-withdrawing group (NO2) in the aromatic
moiety (entry 19, Table 1) did not respond at all under the
reaction conditions.
The reaction initially underwent 1,4-addition of the radical
species followed by ꢀ-acetoxy elimination.15 During the course
of the reaction, it was observed that benzyl bromides provided
the desired products in good yields, whereas allyl bromides gave
moderate yields of the products (entries 7 and 11, Table 1).
Elimination of the OMs group is also as efficient as the OAc
group leading to the desired alkene (entry 1, Table 1). The
stereochemistry of the product is governed by the electron-
withdrawing groups present in the adducts. The E- and Z-
selectivity can be rationalized from the difference in stability
of the chelated (A) and nonchelated (B) transition states (Figure
1) as reported by Basavaiah5 and Das9 in similar transformations.
The E/Z ratio was determined from the 1H NMR spectra of the
crude products. The stereochemistry of the products was
established by comparing the NMR value of the olefinic proton
with the reported values.4–6
activated and nonactivated bromo compounds could be utilized.9
But to the best of our knowledge, there is no report to prepare
substituted alkenes regioselectively from Baylis-Hillman ad-
ducts by radical-induced method specially using a Ti(III) species.
Carbon-carbon bond formation through radical reactions
became one of the important powerful tools in organic synthe-
sis.10 It is very effective for the synthesis of variety of complex
natural products due to its mildness and wide range of functional
group tolerance.11
The Baylis-Hillman reaction has already been proved to be
an important tool for providing molecules possessing hydroxy,
alkene or electron withdrawing group in close proximity in a
number of stereoselective processes.12 This prompted us to
explore the radical addition reactions to the Baylis-Hillman
adducts for the synthesis of valuable intermediates using
titanocene(III) chloride (Cp2TiCl) as the radical generator.13 We
report herein the radical-induced addition of the activated bromo
compounds14 and epoxides to Baylis-Hillman adducts using
Cp2TiCl to yield selectively (E)- and (Z)-trisubstituted alkenes
(Scheme 1) and R-methylene/arylidene δ-lactones (Scheme 3)
respectively in satisfactory yields.
Thus, the treatment of 3-acetoxy-2-methylenealkanoates with
activated bromo or iodo compounds using Ti(III) species as the
radical initiator provided E-2-substituted 2-alkenoates exclu-
sively, whereas 3-acetoxy-2-methylenealkanenitriles furnished
FIGURE 1. Chelated and nonchelated transition states of the alkenoate
and alkenenitrile.
(9) Das, B.; Banerjee, J.; Mahender, G.; Majhi, A. Org. Lett. 2004, 6, 3349.
(10) (a) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis;
Pergamon: Oxford, U. K., 1992. (b) Leonard, J.; Diez-Barra, F.; Merino, S. Eur.
J. Org. Chem. 1998, 2051.
R-Methylene/arylidene δ-lactone is found to be an important
structural fragment in a wide range of natural occurring
biologically active compounds.16 In addition, these lactones are
used as valuable synthetic intermediates toward natural prod-
ucts.17 Over the past decades, considerable efforts have been
devoted to the synthesis of R-methylene/arylidene δ-lactones
by numerous approaches, more significantly toward R-methylene
δ-lactones.18 Basavaiah et al. have reported an excellent method
(11) (a) Giese, B. Radicals In Organic Synthesis, Formation of Carbon-Carbon
Bonds; Pergamon Press: Oxford, 1986. (b) Jasperse, C. P.; Curran, D. P.; Fevig,
T. L. Chem. ReV. 1991, 91, 1237. (c) Motherwell, W. B.; Crich, D. Free Radical
Chain Reactions in Organic Synthesis; Academic: London, 1991. (d) Fossey,
J.; Lefort, D.; Sorba, J. Free Radicals In Organic Chemistry; Wiley: New York,
1995. (e) Ramaiah, M. Tetrahedron 1987, 43, 3541. (f) Srikrishna, A. Curr.
Sci. 1987, 56, 392.
(12) (a) Drewes, S. E.; Ross, G. H. P. Tetrahedron 1988, 44, 4653. (b)
Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. ReV. 2003, 103, 811.
(13) (a) RajanBabu, T. V.; Nugent, W. A. J. Am. Chem. Soc. 1994, 116,
986. and references cited therein. (b) Cuerva, J. M.; Justicia, J.; Oller-Lo´pez,
J. L.; Oltra, J. E. Top. Curr. Chem. 2006, 264, 63. (c) Barrero, A. F.; Qu´ılez del
Moral, J. F.; Sa´nchez, E. M.; Arteaga, J. F. Eur. J. Org. Chem. 2006, 1627. (d)
Gansa¨uer, A. Synlett 1998, 801. (e) Gansa¨uer, A.; Bluhm, H. Chem. Commun.
1998, 2143. (f) Gansa¨uer, A.; Lauterbach, T.; Bluhm, H.; Noltemeyer, M. Angew.
Chem., Int. Ed. 1999, 38, 2909. (g) Gansa¨uer, A.; Lauterbach, T.; Narayan, S.
Angew. Chem., Int. Ed. 2003, 42, 5556. (h) Journet, M.; Malacria, M. J. Org.
Chem. 1994, 59, 718. (i) Devin, P.; Festerbank, L.; Malacria, M. J. Org. Chem.
1998, 63, 6764.
(15) Justicia, J.; Oller-Lo´pez, J. L.; Compana, A. G.; Oltra, J. E.; Cuerva,
J. M.; Bun˜uel, E.; Cardenas, D. J. J. Am. Chem. Soc. 2005, 127, 14911.
(16) (a) Kupchan, S. M.; Hemingway, R. J.; Werner, D.; Karim, A.; McPhail,
A. T.; Sim, G. A. J. Am. Chem. Soc. 1968, 90, 3596. (b) Kupchan, S. M.; Eakin,
M. A.; Thomas, M. A. J. Med. Chem. 1971, 14, 1147. (c) Weinheimer, A. J.;
Matson, J. A.; Hossain, M. B.; van der Helm, D. Tetrahedron Lett. 1977, 2923.
(d) Cane, D. E.; Rossi, T. Tetrahedron Lett. 1979, 2973. (e) Imai, H.; Suzuki,
K.; Morioka, M.; Numasaki, Y.; Kadota, S.; Nagai, K.; Sato, T.; Iwanami, M.;
Saito, T. J. Antibiot. 1987, 40, 1475. (f) McMurry, J. E.; Dushin, R. G. J. Am.
Chem. Soc. 1990, 112, 6942. (g) Nangia, A.; Prasuna, G.; Rao, P. B. Tetrahedron
1997, 53, 14507. (h) Liao, X.-B.; Han, J.-Y.; Li, Y. Tetrahedron lett. 2001, 42,
2843.
(14) (a) Jana, S.; Guin, C.; Roy, S. C. Tetrahedron Lett. 2004, 45, 6575. (b)
Mandal, S. K.; Jana, S.; Roy, S. C. Tetrahedron Lett. 2005, 46, 6115. (c) Paira,
M.; Banerjee, B.; Jana, S.; Mandal, S. K.; Roy, S. C. Tetrahedron Lett. 2007,
48, 3205. (d) Mandal, S. K.; Roy, S. C. Tetrahedron Lett. 2007, 48, 4131.
(17) Liu, Z.-Y.; Zhao, L.-Y. Tetrahedron Lett. 1999, 40, 5593.
3824 J. Org. Chem. Vol. 73, No. 10, 2008

Synthesis of (E)- and (Z)-Trisubstituted Alkenes
TABLE 1. Ti(III)-Mediated Synthesis of Alkenes from Baylis-Hillman Adduct
c
a Products were characterized by IR, NMR and HRMS studies. b Yields refer to pure isolated products. Isomeric ratio was determined from H NMR
1
data.
for the synthesis of bis-lactones from the Baylis-Hillman
two separate doublets. We extended this methodology using
different types of epoxides and 3-aryl-substituted 3-acetoxy-2-
methylenepropanoates to furnish δ-lactones in moderate yields
and the results are summarized in Table 2. The 1H NMR signal
for the ꢀ-substituted proton around δ 7.80-8.00 suggests the
E-selectivity (96 to 100%). It is presumed that the presence of
the carbomethoxy group directs the -OAc elimination as
observed in the case of addition of activated bromo compounds
to Baylis-Hillman adducts. On the other hand, the reaction of
the epoxide 2c with 3-acetoxy-2-methylenenitrile 6a furnished
the nitrile 17 as an inseparable mixture of E- and Z-isomers in
adducts.19 In this paper, we disclose a brilliant synthetic
methodology leading to R-methylene/arylidene δ-lactones in one
pot using titanocene(III)-mediated radical-induced addition of
epoxides to Baylis-Hillman adducts .
Thus, as a representative example, epoxide 1c on treatment
with Cp2TiCl in THF underwent Michael addition with 3-ac-
etoxy-2-methylenepropanoate 1a followed by in situ lactoniza-
tion afforded finally the lactone 1d in 62% yield (Table 2, entry
1). Lactone 1d displayed the IR absorption at 1724 cm-1 and
1H NMR signals for two olefinic protons at δ 5.47 and 6.36 as
J. Org. Chem. Vol. 73, No. 10, 2008 3825

Mandal et al.
TABLE 2. Ti(III)-Mediated Synthesis of δ-Lactones from Baylis-Hillman Adduct
a All products were characterized from NMR, IR, and HRMS data. b Yields refers to pure isolated product. c Cis/trans mixture at the ring junction.
SCHEME 4. Ti(III)-Mediated Addition of Epoxide to
a ratio of 84:16 in 61% yield (Scheme 4). The ratio isomers in
Alkenenitrile
17 was determined from the only distinguishable signal at δ
3.82 (s, OMe for the minor isomer) and 3.85 (s, OMe for the
major isomer) in the 1H NMR spectrum. Since the two isomers
could not be separated by usual chromatographic methods, it is
not possible to determine in this stage which isomer is which.
(18) (a) Jones, E. R. H.; Shen, T. Y.; Whiting, M. C. J. Chem. Soc. 1950,
Disubstuted epoxides such as cyclohexe epoxide 7c also reacted
in a similar fashion with Baylis-Hillman ester 5a to obtain the
lactone 14d as a mixture of two isomers (1:1.5) with respect to
the ring junction (entry 14, Table 2). The major trans isomer in
14d was separated by fractional crystallization, and the NMR
data was compared with the reported values.18d The minor cis
isomer could not be obtained in pure form; it was always
contaminated with the major isomer. Similarly, reaction of 2a
with 7c in the presence of Ti(III) species gave 15d as a mixture
of two isomers in a ratio of 1:1.1 (entry 15, Table 2). The major
trans isomer was separated by fractional crystallization, but the
minor cis isomer could not be obtained in pure form. The
230. (b) Baldwin, S. W.; Crimmins, M. T.; Cheek, V. I. Synthesis 1978, 210.
(c) Ghera, E.; Yechezkel, T.; Hassner, A. J. Org. Chem. 1990, 55, 5977. (d)
Liang, K.-W.; Li, W.-T.; Peng, S.-M.; Wang, S.-L.; Liu, R.-S. J. Am. Chem.
Soc. 1997, 119, 4404. (e) Chandrasekharam, M.; Chang, S.-T.; Liang, K.-W.;
Li, W.-T.; Liu, R.-S. Tetrahedron lett. 1998, 39, 643. (f) Leroy, B. Tetrahedron
Lett. 2005, 46, 7563. (g) Kim, E. J.; Ko, S. Y. Bioorg. Med. Chem. 2005, 13,
4103. (h) Matsuda, I. J. Organomet. Chem. 1987, 321, 307. (i) Grieco, P. A.
Synthesis 1975, 67. (j) Demuth, M.; Schaffner, K. Angew. Chem., Int. Ed. Engl.
1982, 21, 820. (k) Tomioka, K.; Masumi, F.; Yamashita, T.; Koga, K.
Tetrahedron lett. 1984, 25, 333. (l) Righby, J. H.; Wilson, J. Z. J. Am. Chem.
Soc. 1984, 106, 8217. (m) Kallmerten, J.; Gould, T. J. J. Chem. Soc 1985, 50,
1128. (n) Falsone, G.; Wingen, U. Tetrahedron lett. 1989, 30, 675. (o) Krawczyk,
H.; Sliwinski, M.; Wolf, W. M.; Bodalski, R. Synlett 2004, 1995. (p) Raju, R.;
Allen, L. J.; Le, T.; Taylor, C. D.; Howell, A. R. Org. Lett. 2007, 9, 1699. (q)
Gupta, A.; Vankar, Y. D. Tetrahedron 2000, 56, 8525.
(19) Basavaiah, D.; Satyanarayana, T. Org. Lett. 2001, 3, 3619.
3826 J. Org. Chem. Vol. 73, No. 10, 2008

Synthesis of (E)- and (Z)-Trisubstituted Alkenes
144.2 appeared with low intensity for the E-isomer]; HRMS calcd
for C18H16ClNNa [M + Na]+ 304.0869, found 304.0866.
epoxide 8c with an electron-withdrawing group also gave the
desired addition product 16d when reacted with 4a (entry 16,
Table 1).
Typical Procedure for the Synthesis of r-Methylene/Arylidene
δ-Lactones. To a well-stirred solution of epoxide 1c (198 mg, 1
mmol) and Baylis-Hillman adduct 1a (158 mg, 1 mmol) in dry
deoxygenated THF was added dropwise a green solution of Cp2TiCl
(2.1 mmol) (prepared in the same way as described above) in dry
deoxygenated THF over 10 h under argon. After 2 h (monitored
by TLC), the reaction mixture was quenched slowly with 20%
H2SO4. Most of THF was removed under reduced pressure, and
resulting residue was extracted with diethyl ether (3 × 25 mL).
The organic layer was washed successively with water (2 × 10
mL) and brine (2 × 10 mL) and finally dried (Na2SO4). The solvent
was removed under reduced pressure, and the crude material
obtained was purifed by column chromatography over silica gel
(7% ethyl acetate in light petroleum) to furnish 5-(5-chloro-2-
methoxybenzyl)-3-methylidenetetrahydro-2H-pyran-2-one (1d): col-
orless crystalline solid; mp 116-118 °C; IR (KBr) 1724, 1627,
In summary, we have developed a novel protocol for the
radical-induced synthesis of substituted alkenes stereoselectively
by the reaction of activated bromo compounds with Baylis-
Hillman adducts using titanocene(III) chloride as the radical
initiator. This methodology provided stereoselective products
depending on the functionality present in the adducts. We have
also extended this titanium mediated radical technology toward
efficient synthesis of R-methylene/arylidene δ-lactones by
addition of the epoxides to Baylis-Hillman adducts.
Experimental Section
Typical Procedure for the Synthesis of (E)- and (Z)-Trisubsti-
tuted Alkenes. To a stirred solution of Cp2TiCl2 (523 mg, 2.1 mmol)
in deoxygenated THF (26 mL) with activated Zn dust (262 mg, 4
mmol) (activated zinc dust was prepared by washing 20 g of
commercially available zinc dust with 60 mL of 4 N HCl followed
by thorough washing with water until the washings became neutral
and finally washing with dry acetone and then drying in vacuo)
was added, and the stirring was continued for another 1 h to get a
green solution. This green solution was transferred to a dropping
funnel via cannula and was added dropwise over 10 h to a solution
of benzyl bromide (171 mg, 1 mmol) and 2-acetoxymethylacrylic
acid methyl ester (1a) (158 mg, 1 mmol) in deoxygenated THF
(12 mL) under argon. After 2 h (monitored by TLC), the reaction
was quenched slowly with 10% H2SO4. Most of THF was removed
under reduced pressure, and the resulting residue was extracted with
diethyl ether (3 × 25 mL). The organic layer was washed
successively with water (2 × 10 mL) and brine (2 × 10 mL) and
finally dried (Na2SO4). The solvent was removed under reduced
pressure, and the crude material obtained was purifed by column
chromatography over silica gel (3% ethyl acetate in light petroleum)
to furnish methyl 2-methylidene-4-phenylbutanoate (2b) (123 mg,
65%) as a colorless oil: IR (neat) 1720, 1631, 1496 cm-1; 1H NMR
(300 MHz, CDCl3) δ 2.54 (t, J ) 8.4 Hz, 2H), 2.72 (t, J ) 8.4 Hz,
2H), 3.69 (s, 3H), 5.43 (s, 1H), 6.01 (s, 1H), 7.10-7.13 (m, 3H),
7.18-7.23 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 34.0, 35.0, 52.0,
125.5, 126.1, 128.5 (2C), 128.6 (2C), 140.0, 141.5, 167.7; HRMS
calcd for C12H14O2Na [M + Na]+ 213.0892, found 213.0887.
Methyl (2E)-2-(4-chlorobenzylidene)-4-phenylbutanoate (6b):
1
1490, 1247 cm-1; H NMR (300 MHz, CDCl3) δ 2.25-2.35 (m,
2H), 2.46-2.63 (m, 3H), 3.73 (s, 3H), 4.00 (dd, J ) 9.1, 10.3 Hz,
1H), 4.24 (br d, J ) 10.3 Hz, 1H), 5.47 (d, J ) 1.2 Hz, 1H), 6.36
(d, J ) 0.9 Hz, 1H), 6.72 (d, J ) 8.7 Hz, 1H), 6.98 (d, J ) 2.4 Hz,
1H), 7.11 (dd, J ) 2.4, 8.7 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ 31.7, 33.5, 34.1, 55.6, 73.2, 111.6, 125.2, 127.7, 128.5, 129.0,
130.4, 133.1, 156.1, 165.4; HRMS calcd for C14H15ClO3Na [M +
Na]+ 289.0607, found 289.0604.
(3E,4aR,8aS)-3-(4-Chlorobenzylidene)octahydro-2H-chromen-
2-one (15d): colorless crystalline solid; mp 182-184 °C; IR (KBr)
1
1697, 1608, 1245, 1191 cm-1; H NMR (300 MHz, CDCl3) δ
1.06-1.74 (m, 6H), 1.85-1.92 (m, 2H), 2.17 (brd, J ) 10.8 Hz,
1H), 2.31-2.42 (m, 1H), 2.87 (dd, J ) 3.2, 16.5 Hz, 1H), 3.99
(ddd, J ) 4.2, 10.4, 12.7 Hz, 1H), 7.37 (brs, 4H), 7.83 (brs, 1H);
13C NMR (75 MHz, CDCl3) δ 24.0, 25.0, 31.2, 32.2, 33.3, 38.5,
81.9, 126.5, 128.9(2C), 131.5(2C), 133.6, 135.2, 139.9, 167.0;
HRMS calcd for C16H17ClO2Na [M + Na]+ 299.0815, found
299.0818.
(2Z)-2-Benzylidene-5-hydroxy-4-(2-methoxybenzyl)pentaneni-
trile (17): colorless oil; IR (KBr) 3452, 2210, 1494, 1244 cm-1
;
1H NMR (300 MHz, CDCl3) δ 2.18-2.29 (m, 1H), 2.47 (dd, J )
6.7, 13.9 Hz, 1H), 2.61-2.81 (m, 3H), 3.43-3.53 (m, 2H), [3.82
(s, OMe for the minor isomer) and 3.85 (s, OMe for the major
isomer), total 3H], 6.87-6.95 (m, 2H), 7.01 (s, 1H), 7.16-7.24
(m, 2H), 7.36-7.43 (m, 3H), 7.74 (d, J ) 7.8 Hz, 2H); 13C NMR
(75 MHz, CDCl3): δ 30.6, 38.5, 40.6, 55.6, 60.6, 109.9, 110.6,
118.9, 121.1, 127.8, 127.9, 128.7(2C), 128.9(2C), 130.0, 131.2,
1
colorless oil; IR (neat) 1712, 1490 cm-1; H NMR (300 MHz,
133.8, 145.0, 157.4; HRMS calcd for C20H22NO2 [M
+
CDCl3) δ 2.79-2.83 (m, 4H), 3.84 (s, 3H), 7.16-7.22 (m, 5H),
7.26-7.33 (m, 4H), 7.65 (s, 1H); 13C NMR (75 MHz, CDCl3) δ
29.7, 35.2, 52.2, 126.2 (2C), 128.6 (3C), 128.8 (2C), 130.4 (2C),
133.2, 134.1, 134.4, 138.6, 141.3, 168.6; HRMS calcd for
C18H17ClO2Na [M + Na]+ 323.0815, found 323.0821.
H]+308.1651, found 308.1643.
Acknowledgment. We thank the Department of Science and
Technology, New Delhi, for financial assistance. S.K.M. and
M.P. thank CSIR, New Delhi, for awarding fellowships.
4-(4-Chlorophenyl)-2-(4-methylbenzylidene)butanenitrile (9b):
1
crystalline solid; mp 76-78 °C; IR (neat) 2206, 1490 cm-1; H
Supporting Information Available: General experimental
procedures and spectroscopic data. Copies of 1H NMR spectra
of 1b-15b, 1d-16d, and 17 and 13C NMR spectra of
1b-15b,1d-16d, and 17. This material is available free of
charge via the Internet at http://pubs.acs.org.
NMR (300 MHz, CDCl3) δ 2.28 (s, 3H), 2.56 (t, J ) 7.7 Hz, 2H),
2.84 (t, J ) 7.7 Hz, 2H), 6.68 (s, 1H), 7.02-7.18 (m, 6H), 7.48 (d,
J ) 8.0 Hz, 2H) [in addition, only one distinguishable signal at δ
2.65 (t, J ) 8.2 Hz) appeared with low intensity for the E-isomer];
13C NMR (75 MHz, CDCl3) δ 20.4, 32.9, 37.0, 107.6, 117.8, 127.5
(2C), 127.6 (2C), 128.5 (2C), 128.9 (2C), 129.7, 131.1, 137.3, 139.5,
143.4 [in addition, four distinguishable signals at δ 20.3, 30.0, 32.4,
JO800049P
J. Org. Chem. Vol. 73, No. 10, 2008 3827