Pd-catalyzed decarboxylative allylic coupling of acetates of Baylis-Hillman alcohols with propiolic acids: A highly regio- and stereoselective synthesis of 1,5-diarylpent-1-en-4-yne derivatives

Article abstract of DOI:10.1039/c5ra06168g

Pd-catalyzed decarboxylative allylic coupling of acetates of Baylis-Hillman alcohols with alkynyl carboxylic acids leading to the formation of an important class of 1,5-diarylpent-1-en-4-ynes in a highly regio- and stereoselective manner has been develope

Full text of DOI:10.1039/c5ra06168g

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Pd-catalyzed decarboxylative allylic coupling of
acetates of Baylis–Hillman alcohols with propiolic
acids: a highly regio- and stereoselective synthesis
of 1,5-diarylpent-1-en-4-yne derivatives†
Cite this: RSC Adv., 2015, 5, 49392
Received 7th April 2015
Accepted 27th May 2015
*
Satyanarayana Tummanapalli, Parthasarathy Muthuraman,
DOI: 10.1039/c5ra06168g
Dhanunjaya Naidu Vangapandu, Gnanakalai Shanmugavel, Sanjeeva Kambampati
and Kee Wei Lee
www.rsc.org/advances
Pd-catalyzed decarboxylative allylic coupling of acetates of Baylis– Hillman adducts in many organic transformations have been
Hillman alcohols with alkynyl carboxylic acids leading to the well documented.5 In continuation of our interest in the
formation of an important class of 1,5-diarylpent-1-en-4-ynes in a decarboxylative coupling and studies in the application of
highly regio- and stereoselective manner has been developed. Baylis–Hillman adducts in various synthetic organic trans-
Decarboxylative coupling happened via an exclusively SN20 pathway. formations6 we herein report Pd-catalyzed decarboxylative SN20
Acetates of the Baylis–Hillman alcohols derived from alkyl acrylates, allylic coupling of acetates of the Baylis–Hillman alcohols with
ethyl vinyl ketone and phenyl vinyl sulfone provided exclusively (E)- the alkynyl carboxylic acids leading to the formation of
1,5-diarylpent-1-en-4-ynes while the acetates of the Baylis–Hill- important class of 1,5-diarylpent-1-en-4-ynes in a highly regio-
man alcohols derived from acrylonitrile provided exclusively (Z)-1,5- and stereoselective manner. To the best our knowledge there is
diarylpent-1-en-4-ynes.
no study reported on the Pd-catalyzed decarboxylative allylic
coupling of alkynyl carboxylic with acetates of Baylis–Hillman
adducts.7,8 Furthermore, SN20 Pd-catalyzed decarboxylative
addition of alkynyl carboxylic on allylic acetate has also not
been described.9 In addition, 1,5-diarylpent-1-en-4-yne is an
important structural moiety present in the extracts of some
medicinal plants.10 Rooperol (1a), hypoxoside (1b) and many
other 1,5-diarylpent-4-yne-1,2-diol derivatives found in plant
extracts which were reported to exhibit medicinal properties
such as anticancer, anti-inammatory, antibacterial, and
antioxidant activity (Fig. 1).10
Being interested in the decarboxylative coupling and the
development of new synthetic methodologies particularly
using Baylis–Hillman adducts, we studied the Pd-catalyzed
decarboxylative allylic coupling of acetates of the Baylis–Hill-
man alcohols with the alkynyl carboxylic acids. Accordingly,
we subjected allyl acetate 2a11 and phenyl propiolic acid 3a to
Due to the many advantages over traditional oxidative
coupling reactions,1,2 decarboxylative cross coupling reactions
have become an important tool for the construction of carbon–
carbon bonds in modern synthetic organic chemistry. Decar-
boxylative cross coupling reactions employ more stable and
inexpensive carboxylic acids as key reaction partners while
traditional coupling reactions have typically involved expen-
sive and usually air-sensitive organometallic species as their
reaction partners.1,2 Recently alkynyl carboxylic acids have
been inducted into decarboxylative coupling partners by
providing aryl alkyne derivatives.3 In 2008, Lee et al. reported
rst decarboxylative coupling of alkynyl carboxylic acids with
aryl halides.3a Later Li et al. expanded the scope of substrates
to benzyl chlorides, bromides, and acetate in this coupling by
providing desired benzyl alkynes.3e Tunge and co-workers
independently reported the rst intramolecular Pd-catalyzed
decarboxylative allylic rearrangement of allyl alkynoates in
2005.4 The Baylis–Hillman reaction is another important atom-
economical carbon–carbon bond forming reaction providing
densely functionalized molecules. Applications of Baylis–
decarboxylative coupling conditions using of
a catalyst
combination of 5 mol% of Pd(OAc)2 and 10 mol% of S-Phos at
Albany Molecular Research Singapore Research Center, 61 Science Park Road, #03-13
The Galen, Singapore Science Park II, Singapore 117525. E-mail:
satyatummanapalli@yahoo.com
† Electronic supplementary information (ESI) available: Experimental procedures,
1H NMR, 2D NOESY, 13C NMR and MS data of all the products. See DOI:
10.1039/c5ra06168g
Fig. 1 Structures of rooperol (1a) and hypoxoside (1b).
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Table 1 Regio- and stereo-selective Pd-catalyzed allylic decarboxylative coupling of methyl acrylate derived acetates 2b–e leading to the
formation of (E)-1,5-diarylpent-1-en-4-ynes 4a–i
Entry
1
Acetatea
Propiolic acid
Product(s)b
Yieldc (%)
86
2
3
4
3a
81
86
82
2b
3b
3b
5
6
7
2d
2c
79
85
78
3a
3c
8
2e
83
a
b
Acetates of Baylis–Hillman alcohol 2b–e were prepared by following the typical procedure described in ref. 11. Reactions were carried out
c
following the typical procedure described in ref. 12. Isolated yields aer chromatographic purication on silica gel.
70 ꢀC. Work-up and silica gel column chromatography regio- and stereoselective manner via exclusively SN20 allylic
provided (E)-methyl-2-(4-methylbenzylidene)-5-phenylpent-4- pathway.
ynoate (4a) as the exclusive isolated product in 88%
The E-stereochemistry was assigned based on the literature
yield.12,13 Proton NMR analysis of the crude reaction mixture precedence of E/Z-stereochemical assignments of 3-aryl-(2-
did not indicate the presence of other regioisomer 6 or the substituted)-prop-2-enoates.14 The E-stereochemistry of 4a was
corresponding Z-isomer 5. Formation of exclusively E-isomer further ascertained by 2D NOESY. A strong NOE cross peak
4a suggests that decarboxylative coupling between allyl between the CH2 (allylic methylene proton) and Ar-Hortho (ortho
acetate 2a and phenyl propiolic acid 3a happened in a highly proton of the benzene ring) was observed, while there was
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no (or a weak) NOE correlation between the CH2 (allylic 90% yield.16 (Scheme 2). Proton NMR analysis of the crude
methylene) and CH (olenic proton of the double bond). reaction mixture did not indicate the presence of other
To provide the generality of the palladium-catalyzed allylic regioisomer 10 or the corresponding E-isomer 9. Again,
decarboxylative coupling, other acetates 2b–e were treated formation of exclusively Z-isomer 8a clearly suggests that, in
with propiolic acids 3a–c in the presence of 5 mol% of acrylonitrile derived acetate 7a case too, decarboxylative
Pd(OAc)2 and 10 mol% of S-Phos following the standard coupling happened regioselectively via exclusively SN20
reaction procedure.12 The crude products, obtained aer usual pathway. However, in contrast to the methyl acrylate derived
work-up, were puried by silica gel chromatography to furnish acetates (2a–e, Scheme 1 and Table 1), in this case (acryloni-
pure (E)-1,5-diarylpent-1-en-4-yne derivatives 4b–i in high trile derived acetate 7a), the isolated product 8a was formed
yields (Table 1).
with a shi in the stereoselectively, i.e., from E to Z (Scheme 2).
Encouraged by these results, we extended our studies to the The Z-stereochemistry in the case of 8a was ascertained by 2D
acetates of Baylis–Hillman adducts derived from acrylonitrile. NOESY experiments where a strong NOE cross peak was
Accordingly, we subjected acetate 7a (derived from Baylis– observed between the CH2 (allylic methylene proton) and CH
Hillman alcohol of benzaldehyde and acrylonitrile)15 to (olenic proton of the double bond), while there was no (or a
decarboxylative coupling with phenyl propiolic acid 3a using a weak) NOE correlation between the CH2 (allylic methylene
catalyst combination of 5 mol% of Pd(OAc)2 and 10 mol% of S- proton) and Ar-Hortho (ortho proton of the benzene ring). To
Phos following the standard reaction procedure.16 Work-up expand the substrate scope, we treated other acrylonitrile
and silica gel column chromatography provided exclusively derived acetates 7a–f12 to stereoselective SN20 allylic decarbox-
(Z)-2-(4-methoxybenzylidene)-5-phenylpent-4-ynenitrile (8a) in ylative coupling with aryl propiolic acids 3a–c (Table 2).
Upon standard work-up and silica gel chromatographic puri-
cation, pure (Z)-1,5-diarylpent-1-en-4-yne derivatives 8b–k
were isolated in high yields with exclusively Z-stereochemistry
(Table 2).16
Being fascinated by reversal in the stereochemistry when
EWG (electron withdrawing group) was changed from methyl
ester to cyano group and to understand the effect of other EWG
on the stereochemical outcome in this Pd-catalyzed allylic
decarboxylative coupling, we further extended our studies to
the acetates of Baylis–Hillman adducts derived from other
EWG (ketone, sulfone, other esters etc.). Accordingly, we sub-
jected acetate 11 derived from Baylis–Hillman alcohol of
benzaldehyde and ethyl vinyl ketone11 to decarboxylative
coupling with aryl propiolic acids 3a and 3c using standard
reaction procedure.16 Work-up and silica gel column chroma-
tography provided corresponding products 14 and 15 exclu-
sively with (E)-stereoselectivity (Table 3). Proton NMR analysis
of the crude reaction mixture did not indicate the presence of
Scheme 1 Regio- and stereo-selective Pd-catalyzed allylic decar-
boxylative coupling of methyl acrylate derived acetate 2a leading to
the formation of exclusively E-isomer 4a.12
Z-isomer. Similarly, acetate 12 derived from Baylis–Hillman
alcohol of 4-methylbenzaldehyde and ethyl acrylate11 provided
corresponding products 16 and 17 exclusively with (E)-stereo-
selectivity (Table 3). Again, proton NMR analysis of the crude
reaction mixture did not indicate the presence of Z-isomer.
Finally, we extended our studies to Baylis–Hillman acetates
13a–b derived from phenyl vinyl sulfone11 to decarboxylative
coupling with aryl propiolic acids 3a and 3c using standard
reaction procedure.12 Work-up and silica gel column chroma-
tography provided corresponding products 18 and 19 exclu-
sively with (E)-stereoselectivity (Table 3). Formation of
exclusively E-isomers 14–19 clearly suggests that the decar-
boxylative coupling happened regioselectively via exclusively
SN20 pathway in the case of electron withdrawing groups (EWG)
such as ethyl vinyl ketone (11), ethyl acrylate (12) and phenyl
vinyl sulfone (13). However, unlike the cyano group (Scheme 2,
Table 2), the electron withdrawing group, ethyl vinyl ketone
(11) and phenyl vinyl sulfone (13) and ethyl acrylate (12)
provided similar E-stereoselectivity like the methyl acrylate
(Scheme 1, Table 1).
Scheme 2 Regio- and stereo-selective Pd-catalyzed allylic decar-
boxylative coupling of acrylonitrile derived acetate 7a leading to the
formation of exclusively Z-isomer 8a.16
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Table 2 Regio- and stereo-selective Pd-catalyzed allylic decarboxylative coupling of acrylonitrile derived acetates 7a–f leading to the formation
of (Z)-1,5-diarylpent-1-en-4-ynes 8a–k
Entry
1
Acetatea
Propiolic acid
Product(s)b
Yieldc (%)
79
2
3a
3a
83
3
4
87
80
7b
5
6
7d
7c
3b
82
81
7
8
9
3a
3c
3a
78
80
82
7e
10
7f
3c
84
a
b
Acetates of Baylis–Hillman alcohol 7a–f were prepared by following the typical procedure described in ref. 15. Reactions were carried out
c
following the typical procedure described in ref. 16. Isolated yields aer chromatographic purication on silica gel.
transformations using the Baylis–Hillman adducts.6d,7,18 and
with formation of similar products using other strategies. The
E-selectivity in the case of aryl propiolates of Baylis–Hillman
Transition state models and plausible
explanation of the stereochemical
alcohols derived from methyl acrylate can possibly be
explained using transition state models TS-1a and TS-1b
(Scheme 3, Path-I). Ester, ethyl ketone and phenyl sulfone
switch between the acetates derived
from methyl acrylate and acrylonitrile
groups are relatively bulkier and exert more steric effect on
aryl group in TS-1a than the methylene group on aryl group in
The stereochemical reversal from an ester group to a cyano
group is consistent with earlier reports on other synthetic
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Table 3 Regio- and stereoselective Pd-catalyzed allylic decarboxylative coupling of Baylis–Hillman acetates derived from other EWG; ethyl vinyl
ketone (11), ethyl acrylate (12) and phenyl vinyl sulfone (13a, 13b)
Entry
1
Acetatea
Propiolic acid
Product(s)b
Yieldc (%)
78
2
3
4
5
11
80
83
85
79
3a
3c
3c
12
6
3c
85
a
b
Acetates of Baylis–Hillman alcohol 11, 12, 13a and 13b were prepared by following the typical procedure described in ref. 11. Reactions were
c
carried out following the typical procedure described in ref. 12. Isolated yields aer chromatographic purication on silica gel.
TS-1b. Therefore, product will form via more favoured tran- coupling between acetates of the Baylis–Hillman alcohols and
sition state TS-1b leading to the formation of E-isomer. Simi- aryl propiolic acids leading to the formation of important
larly, The Z-selectivity in the case of aryl propiolates of Baylis– classes of 1,5-diarylpent-1-en-4-ynes with exclusively E- or
Hillman alcohols derived from acrylonitrile can be explained Z-selectivity. Acetates of the Baylis–Hillman alcohols derived
by transition state models TS-2a and TS-2b (Scheme 3, Path-II). from alkyl acrylates, ethyl vinyl ketone and phenyl vinyl sulfone
Being a small linear group, CN group will have relatively lower provide exclusively (E)-1,5-diarylpent-1-en-4-ynes and the
steric effect on aryl group in TS-2a when compared to the acetates obtained from acrylonitrile provide exclusively (Z)-1,5-
methylene group on aryl group in TS-2b. Therefore, in this diarylpent-1-en-4-ynes.
case (aryl propiolates of Baylis–Hillman alcohols derived from
acrylonitrile) product will form via more favoured transition
state TS-2a leading to the formation of Z-isomer.
Acknowledgements
We sincerely appreciate the nancial support from Albany
Conclusions
Molecular Research Inc. The authors also thank Dr Anjan
In conclusion, we have developed a highly regio- and stereo- Chakrabarti for his support during the preparation of this
selective palladium-catalyzed SN20 allylic decarboxylative manuscript.
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3 For selected papers on Pd-catalyzed decarboxylative coupling
alkynyl carboxylic acids, see: (a) J. Moon, M. Jeong, H. Nam,
J. Ju, J. H. Moon, H. M. Jung and S. Lee, Org. Lett., 2008, 10,
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2010, 75, 5259–5264.
Scheme 3 Plausible mechanism and transition state models leading
E-selectivity in the case of acetates derived from alkyl acrylates (2a–e,
12) ethyl vinyl ketone (11) and phenyl vinyl sulfone and (13a–b) and
Z-selectivity in the case of acrylonitrile derived acetates 7a–f.
4 D. K. Rayabarapu and J. A. Tunge, J. Am. Chem. Soc., 2005,
127, 13510–13511.
Notes and references
1 For reviews on decarboxylative cross-coupling reactions, see:
(a) K. Park and S. Lee, RSC Adv., 2013, 3, 14165–14182; (b)
L. J. Goossen and K. Goossen, Top. Organomet. Chem.,
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Chem., 2011, 54, 1670–1687; (d) W. I. Dzik, P. P. Lange and
L. J. Goossen, Chem. Sci., 2012, 3, 2671–2678; (e)
5 For reviews on Baylis–Hillman Chemistry and the
application of the Baylis–Hillman adducts, see: (a)
D. Basavaiah and B. C. Sahu, Chimia, 2013, 67, 8–16; (b)
Y. Wei and M. Shi, Chem. Rev., 2013, 113, 6659–6690; (c)
T. Y. Liu, M. Xie and Y. C. Chen, Chem. Soc. Rev., 2012, 41,
4101–4112; (d) D. Basavaiah and G. Veeraraghavaiah,
Chem. Soc. Rev., 2012, 41, 68–78; (e) D. Basavaiah,
B. S. Reddy and S. S. Badsara, Chem. Rev., 2010, 110, 5447–
5674; (f) Y. Wei and M. Shi, Acc. Chem. Res., 2010, 43,
1005–1018; (g) V. Declerck, J. Martinez and F. Lamaty,
Chem. Rev., 2009, 109, 1–48; (h) V. Singh and S. Batra,
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C. Housseman and J. Zhu, Angew. Chem., Int. Ed., 2007, 46,
4614–4628; (j) D. Basavaiah, K. V. Rao and R. Reddy, Chem.
Soc. Rev., 2007, 36, 1581–1588; (k) D. Basavaiah, A. J. Rao
and T. Satyanarayana, Chem. Rev., 2003, 103, 811–891; (l)
E. Ciganek, in Organic Reactions, ed. L. A. Paquette, Wiley,
New York, NY, 1997, vol. 51, pp. 201e350; (m) D. Basavaiah,
P. D. Rao and R. S. Hyma, Tetrahedron, 1996, 52, 8001–
8062; (n) S. E. Drewes and G. H. P. Roos, Tetrahedron, 1988,
44, 4653–4670.
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5030–5048; (f) L. J. Goossen, F. Collet and K. Goossen, Isr.
J. Chem., 2010, 50, 617–629.
2 For selected papers on Pd-catalyzed decarboxylative cross-
coupling reactions, see: (a) L. J. Goossen, K. Goossen,
N. Rodrıguez, M. Blanchot, C. Linder and B. Zimmermann,
Pure Appl. Chem., 2008, 80, 1725–1733; (b) L. J. Goossen,
N. Rodrıguez and K. Goossen, Angew. Chem., Int. Ed., 2008,
47, 3100–3120; (c) H. Tatamidani, K. Yokota, F. Kakiuchi
and N. Chatani, J. Org. Chem., 2004, 69, 5615–5621; (d)
L. J. Goossen, G. Deng and L. M. Levy, Science, 2006, 313,
662–664; (e) P. Forgione, M.-C. Brochu, M. St-Onge,
K. H. Thesen, M. D. Bailey and F. Bilodeau, J. Am. Chem.
Soc., 2006, 128, 11350–11351; (f) A. Maehara, H. Tsurugi,
T. Satoh and M. Miura, Org. Lett., 2008, 10, 1259–1262; (g)
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6 (a) D. Basavaiah, K. Padmaja and T. Satyanarayana,
Synthesis, 2000, 1662–1664; (b) D. Basavaiah and
B. Gilbreath, S. Moharana, K. N. Dalby and S. M. Kerwin,
ChemBioChem, 2013, 14, 66–71.
T. Satyanarayana, Org. Lett., 2001, 3, 3619–3622; (c) 11 Typical procedure for the synthesis of methyl-2-(acetoxy(4-
D. Basavaiah and T. Satyanarayana, Tetrahedron Lett., 2002,
43, 4301–4303; (d) D. Basavaiah and T. Satyanarayana,
Chem. Commun., 2004, 32–33; (e) D. Basavaiah,
B. Devender, D. V. Lenin and T. Satyanarayana, Synlett,
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V. Dhanunjaya Naidu and S. Majumder, Tetrahedron Lett.,
2014, 55, 6787–6790.
7 Very recently our work on a Palladium-catalyzed tandem
intramolecular decarboxylative coupling via the allylic
rearrangement of aryl propiolates derived from the Baylis–
Hillman adducts leading to the formation important class
methoxyphenyl)methyl)acrylate (2a): To a solution of
methyl-2-(hydroxy(4-methoxyphenyl)methyl)acrylate (0.45
mmol) and pyridine (0.90 mmol) in dichloromethane
(5 mL), was added acetyl chloride (0.54 mmol) at 0 ꢀC.
Reaction mixture was allowed to slowly warm to room
temperature while stirring was continued. Upon reaction
completion as judged by TLC, the resulting mixture was
diluted with dichloromethane (10 mL), washed with 2 N
HCl solution (5 mL), satd NaHCO3 solution (5 mL) and
dried over Na2SO4. The organic layer was concentrated
under reduced pressure and puried by column
chromatography on silica (EtOAc–hexanes) to afford methyl-
2-(acetoxy(4-methoxyphenyl)methyl)acrylate 2a (0.42 mmol,
95%). 1H NMR (400 MHz, CDCl3): d 2.07 (s, 3H), 3.68 (s,
3H), 3.77 (s, 3H), 5.86–5.87 (m, 1H), 6.37 (s, 1H), 6.63 (s,
1H), 6.86 (d, J ¼ 8.79 Hz, 2H), 7.28 (d, J ¼ 8.67 Hz, 2H);
13C NMR (100 MHz, CDCl3): d 21.0, 51.9, 55.2, 72.8, 113.8,
125.1, 129.1, 129.8, 139.7, 159.6, 165.4, 169.4; ESI-MS calc.
for C14H17O5 [M + H]+ ¼ 265; found: m/z 265.
of
1,5-diarylpent-1-en-4-ynes
highly
regio-
and
stereoselective manner has acceptedT. Satyanarayana,
V. Dhanunjaya Naidu, M. Parthasarathy and N. Shashidhar,
Tetrahedron Lett., 2015, 56, 2008–2013.
8 During their original study of intramolecular Pd-catalyzed
decarboxylative allylic rearrangement of allyl alkynoates,
Tunge and co-workers also reported two isolated examples
of Pd-catalyzed decarboxylative allylic SN2 type substitution
between two allyl acetates and phenyl propiolic acid.4 In 12 Typical procedure for the synthesis of (E)-methyl-2-(4-
their case, no any coupling involving SN20-type Pd-catalyzed
decarboxylative allylic substitution was observed.
methoxybenzylidene)-5-phenylpent-4-ynoate (4a): To
a
stirred solution of methyl-2-(acetoxy(4-methoxyphenyl)-
methyl)acrylate 2a (0.42 mmol) in dry THF (15 mL), were
added Pd(OAc)2 (0.021 mmol), 2-dicyclohexylphosphino-
20,60-dimethoxybiphenyl (0.042 mmol), Cs2CO3 (0.84 mmol)
and 3-phenylpropiolic acid (0.50 mmol). The mixture was
heated to 70 ꢀC for 30 min. Upon reaction completion as
judged by TLC, the resulting mixture was diluted with
ethyl acetate (10 mL), washed with water (5 mL), brine
(5 mL) and dried over Na2SO4. The organic layer was
concentrated under reduced pressure and puried by
column chromatography on silica (EtOAc–hexanes) to
afford (E)-methyl-2-(4-methoxybenzylidene)-5-phenylpent-4-
ynoate 4a (0.36 mmol, 85%). 1H NMR (400 MHz, CDCl3):
d 3.62 (s, 2H), 3.85 (s, 3H), 3.86 (s, 3H), 6.97 (d, J ¼ 8.83
Hz, 2H), 7.26–7.28 (m, 3H), 7.39–7.42 (m, 2H), 7.58 (d, J ¼
8.71 Hz, 2H), 7.76 (s, 1H); 13C NMR (100 MHz, CDCl3):
d 18.7, 52.2, 55.3, 80.8, 87.2, 114.1, 123.6, 125.4, 127.5,
127.7, 128.1, 131.7, 131.7, 140.5, 160.3, 168.0; ESI-MS calc.
for C19H19O3 [M + H]+: 307; found: m/z 307.
9 Pd-catalyzed allylic substitution involving the attack of
various nucleophiles on an allylic Pd intermediate,
providing SN2 or SN20 substitution products, has been
investigated with great intensity.17
10 1,5-Diarylpent-1-en-4-yne is an important core present in the
extracts of the African potato (Hypoxis hemerocallidea) which
are widely used for a variety of medical conditions. For
details, see: (a) P. M. O. Owira and J. A. O. Ojewole,
Phytother. Res., 2009, 23, 147–296; (b) S. E. Drewes and
F. S. Khan, S. Afr. J. Sci., 2004, 100, 425–430; (c)
G. B. M. Bettolo, M. Patamia, M. Nicoletti, C. Galeffi and
I. Messana, Tetrahedron, 1982, 38, 1683–1687; (d)
S. E. Drewes, A. J. Hall, R. A. Learmonth and U. J. Upfold,
Phytochemistry, 1984, 23, 1313–1316; (e) C. Galeffi,
G. Multari, V. Y. De, I. Messana, M. Nicoletti and
G. B. Marini-Bettolo, Planta Med., 1989, 55, 318–320; (f)
W.-L. Chang, M.-J. Su and S.-S. Lee, J. Nat. Prod., 1997, 60,
76–80; (g) W. L. Chang, C. H. Chen and S. S. Lee, J. Nat.
Prod., 1999, 62, 734–739; (h) K. J. Wang, N. Li and
H. Wang, Molecules, 2008, 13, 1696–1701; (i) G. J. Boukes,
B. B. Daniels, C. F. Albrecht and M. Van de Venter, Oncol.
Res., 2009, 18, 365–376; (j) M. J. Vandermerwe, K. Jenkins,
E. Theron and B. Vanderwalt, Biochem. Pharmacol., 1993,
45, 303–311; (k) M. M. Kabanda, Chem. Res. Toxicol., 2012,
25, 2153–2166; (l) J. Li, T. S. Kaoud, J. LeVieux,
13 Similar compounds were synthesized using the
organometallic species involving different synthetic
strategies such as the addition of (a) alkynyl Grignard on
acetates of the Baylis–Hillman alcohols19a (b) alkynyl
cuprate19b and alkynyl indium19c species on bromides
derived from the Baylis–Hillman alcohols.
14 In 3-aryl-(2-substituted)-prop-2-enoates, the b-vinylic proton
cis to the ester group of the E-isomers appear at d ꢁ 7.7 ppm
while the d-vinylic proton trans to the ester group of the
Z-isomers appear at d ꢁ 6.8 ppm.7,18
15 Typical procedure for the synthesis of 2-cyano-1-(4-
methoxyphenyl)allyl acetate (7a): To a stirred solution of 2-
(hydroxy(4-methoxyphenyl)methyl)acrylonitrile (0.52 mmol),
pyridine (1.04 mmol) in dichloromethane (5 mL), acetyl
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chloride (0.63 mmol) was added at 0 C. Reaction mixture
was allowed to slowly warm to room temperature while
126.0, 128.3, 128.4, 130.6, 131.7, 143.8, 161.2; ESI-MS calc.
for C19H16NO [M + H]+: 274; found: m/z 274.
stirring was continued. Upon reaction completion as 17 For Pd-catalyzed allylic substitution of b-keto acids: (a)
judged by TLC, the resulting mixture was diluted with
dichloromethane (10 mL), washed with 2 N HCl solution (5
mL), satd. NaHCO3 solution (5 mL) and dried over Na2SO4.
The organic layer was concentrated under reduced
pressure and puried by column chromatography on silica
(EtOAc–hexanes) to afford 2-cyano-1-(4-methoxyphenyl)allyl
B. M. Trost and D. L. Van Vranken, Chem. Rev., 1996, 96,
395–422; (b) B. M. Trost, Acc. Chem. Res., 1996, 29, 355–
364; (c) Q.-H. Fan, Y.-M. Li and A. S. C. Chan, Chem. Rev.,
2002, 102, 3385–3466; (d) B. M. Trost and M. L. Crawley,
Chem. Rev., 2003, 103, 2921–2944; (e) B. M. Trost, J. Org.
Chem., 2004, 69, 5813–5837; (f) J. D. Weaver, A. Recio III,
A. J. Grenning and J. A. Tunge, Chem. Rev., 2010, 111,
1846–1913; (g) Z. Lu and S. Ma, Angew. Chem., Int. Ed.,
2008, 47, 258–297; (h) E. C. Burger and J. A. Tunge, Org.
Lett., 2004, 6, 4113–4115; (i) J. A. Tunge and E. C. Burger,
Eur. J. Org. Chem., 2005, 9, 1715–1726; (j) S. R. Mellegaard-
Waetzig, D. K. Rayabarapu and J. A. Tunge, Synlett, 2005,
2759–2762; (k) M. Nakamura, A. Hajra, K. Endo and
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1
acetate 7a (0.69 mmol, 91%). H NMR (400 MHz, CDCl3): d
2.15 (s, 3H), 3.81 (s, 3H), 5.97 (d, J ¼ 1.39 Hz, 1H), 6.05 (d,
J ¼ 1.07 Hz, 1H), 6.28 (s, 1H), 6.90–6.93 (d, J ¼ 8.78 Hz,
2H), 7.32 (d, J ¼ 8.53 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 20.9, 55.3, 74.0, 114.3, 116.3, 123.3, 127.7, 128.5, 131.5,
160.2, 169.2; ESI-MS calc. for C13H14NO3 [M + H]+ ¼ 232;
found: m/z 232.
16 Typical procedure for the synthesis of (Z)-2-(4-
methoxybenzylidene)-5-phenylpent-4-ynenitrile (8a): To a
stirred solution of 2-cyano-1-(4-methoxyphenyl)allyl acetate
7a (0.43 mmol) in dry THF (15 mL), were added Pd(OAc)2
(0.021 mmol), 2-dicyclohexylphosphino-20,60-dimethoxybi-
phenyl (0.042 mmol), Cs2CO3 (0.86 mmol) and 3-
phenylpropiolic acid (0.50 mmol). The mixture was heated 18 (a) D. Basavaiah and P. K. S. Sarma, Chem. Commun., 1992,
to 70 ꢀC for 30 min. Upon reaction completion as judged
by TLC, the resulting mixture was diluted with ethyl
acetate (10 mL), washed with water (5 mL), brine (5 mL)
and dried over Na2SO4. The organic layer was concentrated
955–957; (b) D. Basavaiah, M. Krishnamacharyulu,
R. S. Hyma and S. Pandiaraju, Tetrahedron Lett., 1997, 38,
2141–2144; (c) H. J. Lee, M. R. Seong and J. N. Kim,
Tetrahedron Lett., 1998, 39, 6223.
under reduced pressure and puried by column 19 (a) S. Gowrisankar, K. Y. Lee, C. G. Lee and J. N. Kim,
chromatography on silica (EtOAc–hexanes) to afford (Z)-2-
(4-methoxybenzylidene)-5-phenylpent-4-ynenitrile (8a) (0.38
Tetrahedron Lett., 2004, 45, 6141–6146; (b) J. W. Lim,
K. H. Kim, S. H. Kim and J. N. Kim, Tetrahedron Lett.,
2012, 53, 5449–5454; (c) J. S. Yadav, B. V. S. Reddy,
N. N. Yadav, A. P. Singh, M. Choudhary and A. C. Kunwar,
Tetrahedron Lett., 2008, 49, 6090–6094.
1
mmol, 89%). H NMR (300 MHz, CDCl3): d 3.56 (d, J ¼ 3.0,
Hz, 2H), 3.85 (s, 3H), 6.92–6.95 (m, 2H), 7.31–7.34 (m, 3H),
7.45–7.49 (m, 2H), 7.74–7.77 (m, 2H); 13C NMR (75 MHz,
CDCl3): d 26.2, 55.4, 83.2, 85.5, 103.1, 114.2, 118.7, 122.8,
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