Phosphine-mediated reaction of 3-alkyl allenoates and diaryl 1,2-diones: Efficient diastereoselective synthesis of fully substituted cyclopentenones

Article abstract of DOI:10.1021/ol400467v

An efficient phosphine-mediated diastereoselective synthesis of substituted cyclopentenones from 3-alkyl allenoates and diaryl 1,2-diones is described.

Full text of DOI:10.1021/ol400467v

ORGANIC
LETTERS
2013
Vol. 15, No. 8
1858–1861
Phosphine-Mediated Reaction of 3‑Alkyl
Allenoates and Diaryl 1,2-Diones: Efficient
Diastereoselective Synthesis of Fully
Substituted Cyclopentenones†
Anu Jose,‡ K. C. Seetha Lakshmi,‡ Eringathodi Suresh,§ and Vijay Nair*,‡
Organic Chemistry Section, National Institute for Interdisciplinary Science and
Technology (CSIR), Thiruvananthapuram, India, and Analytical Science Division,
Central Salt and Marine Chemicals Research Institute, Bhavnagar, 364002, India
vijaynair_2001@yahoo.com
Received February 20, 2013
ABSTRACT
An efficient phosphine-mediated diastereoselective synthesis of substituted cyclopentenones from 3-alkyl allenoates and diaryl 1,2-diones is
described.
In recent years, there has been enormous interest in
the chemistry of zwitterionic species1 largely from the
standpoint of their applications in multicomponent reac-
tions (MCRs).2,3 In general, the zwitterions that attracted
most attention are those formed by the addition of nucleo-
philes including nitrogen heterocycles, phosphines, and
isocyanides to activated π-systems such as acetylenic
esters,4 azoesters,5 and allenoates.6 Investigations in a
number of laboratories, including our own, have shown
that zwitterions of the type mentioned above on reaction
with electrophiles give rise to carbo- and heterocyclic
products by 1,3- or 1,4-dipolar cycloadditions. In certain
† Dedicated with best wishes to Professor Goverdhan Mehta on the
occasion of his 70th birthday.
‡ National Institute for Interdisciplinary Science and Technology (CSIR).
§ Central Salt and Marine Chemicals Research Institute.
(1) For reviews, see: (a) Acheson, R. M. Adv. Heterocycl. Chem. 1963,
1, 125. (b) Winterfeidt, E. Angew. Chem., Int. Ed. Engl. 1967, 6, 423. (c)
Huisgen, R. In Topics in Heterocyclic Chemistry; Castle, R., Ed.; John
Wiley and Sons: New York, 1969; Chapter 8, p 223. (d) Nair, V.; Menon,
R. S.; Sreekanth, A. R.; Abhilash, N.; Biju, A. T. Acc. Chem. Res. 2006,
39, 520.
€
(2) For general reviews on MCRs, see: (a) Domling, A.; Ugi, I.
€
Angew. Chem., Int. Ed. Engl. 2000, 39, 3168. (b) Domling, A. Chem.
(4) (a) Diels, O.; Alder, K. Liebigs Ann. Chem. 1932, 498, 16. (b)
Huisgen, R.; Morikawa, M.; Herbig, K.; Brunn, E. Chem. Ber. 1967,
100, 1094. (c) Johnson, A. W.; Tebby, J. C. J. Chem. Soc. 1961, 2126. (d)
Tebby, J. C.; Wilson, I. F.; Grifiths, D. V. J. Chem. Soc., Perkin Trans. 1
1979, 2133. (e) Acheson, R. M.; Plunkett, A. O. J. Chem. Soc. 1964, 2676.
(f) Winterfeldt, E. Chem. Ber. 1964, 97, 1952. (g) Winterfeldt, E.;
Dillinger, H. J. Chem. Ber. 1966, 99, 1558. (h) Winterfeldt, E.; Schu-
mann, D.; Dillinger, H. J. Chem. Ber. 1969, 102, 1656. (i) Dillinger, H. J.;
Fengler, G.; Schumann, D.; Winterfeldt, E. Tetrahedron 1974, 30, 2553
and 2561. (j) Junjappa, H.; Saxena, M. K.; Ramaiah, D.; Lohray, B. B.;
Rath, N. P.; George, M. V. J. Org. Chem. 1998, 63, 9801.
(5) (a) Huisgen, R. In The Adventure Playground of Mechanisms and
Novel Reactions: Profiles, Pathways and Dreams; Seeman, J. I., Ed.;
American Chemical Society: Washington, DC, 1994; p 62. (b) Nair, V.;
Biju, A. T.; Mathew, S. C.; Babu, B. P. Chem.;Asian J. 2008, 3, 810.
(c) Huisgen, R.; Blaschke, H.; Brunn, E. Tetrahedron Lett. 1966, 7, 405.
(d) Brunn, E.; Huisgen, R. Angew. Chem., Int. Ed. 1969, 8, 513. (e)
Mitsunobu, O. Synthesis 1981, 1. (f) Hughs, D. L. Org. Prep. Proced. Int.
1996, 28, 127.
Rev. 2006, 106, 17. (c) Scheffelaar, R.; Ruijter, E.; Orru, R. V. A.
Multicomponent Reaction Design Strategies: Towards Scaffold and
Stereochemical Diversity. Top. Heterocycl. Chem. 2010, 25, 95. (d)
Ramon, D. J.; Yus, M. Angew. Chem., Int. Ed. 2005, 44, 1602. (e)
Zhu, J. Eur. J. Org. Chem. 2003, 1133.
(3) For review and selected reports, see: (a) Nair, V.; Rajesh, C.;
Vinod, A. U.; Bindu, S.; Sreekanth, A. R.; Mathen, J. S.; Balagopal, L.
Acc. Chem. Res. 2003, 36, 899. (b) Nair, V.; Babu, B. P.; Varghese, V.;
Sinu, C. R.; Paul, R. R.; Anabha, E. R.; Suresh, E. Tetrahedron Lett.
2009, 50, 3716. (c) Nair, V.; Deepthi, A.; Beneesh, P. B.; Suresh, E.
Synthesis 2006, 1443. (d) Nair, V.; Devipriya, S.; Suresh, E. Tetrahedron
2008, 64, 3567. (e) Yavari, I.; Mirzaei, A.; Moradi, L.; Khalili, G.
Tetrahedron Lett. 2010, 51, 396. (f) Yavari, I.; Mokhtarporyani-Sanan-
daj, A.; Moradi, L.; Mirzaei, A. Tetrahedron 2008, 64, 5221. (g) Ma, C.;
Ding, H.; Wang, Y. Org. Lett. 2006, 8, 3133. (h) Ma, C.; Yang, Y. W.
Org. Lett. 2005, 7, 1343. (i) Terzidis, M. A.; Stephanidou-Stephanatou,
J.; Tsoleridis, C. A.; Terzis, A.; Raptopoulou, C. P.; Psycharis, V.
Tetrahedron 2010, 66, 947.
r
10.1021/ol400467v
Published on Web 04/09/2013
2013 American Chemical Society

instances, the zwitterion is only an intermediate in a
bond-forming reaction between two electrophiles, with
the nucleophile serving just as a catalyst.
structure and stereochemistry was derived from single-
crystal X-ray analysis of the analogous compound 3b
(vide infra) (Figure 1). In view of the surprising result
and the fact that cyclopentenones are important com-
pounds, it was obligatory to pursue the reaction in some
detail. The reaction was optimized10 by varying solvent,
phosphine, temperature, and time; theresultsare presented
in Table 1.
During the last 10 years, allenoateÀphosphine zwitter-
ions have been extensively investigated by several groups
and their utility has been demonstrated in the construction
of a variety of carbo- and heterocycles.6,7 In the context
of our work on the chemistry of zwitterions as well as
1,2-diones,8 it was of interest to explore the reactivity of
allenoate-phosphine zwitterions toward the latter, a class
of uniquely reactive compounds. It is noteworthy that
although annulation of allenoate-phosphine zwitterions
with aldehydes has been reported by various groups,9 their
reactivity toward 1,2-diones remained unexplored, thus
providing additional impetus for our work. Our studies
leading to an efficient synthesis of fully substituted cyclo-
pentenones are presented in this paper.
Table 1. Optimization of Reaction Conditions
entry solvent
phosphine
PPh3
temp (°C) time (h) yield (%)
The present investigations commenced by the addition of
triphenylphosphine to a solution of allenoate 1and benzil 2in
DCM under argon atmosphere and the mixture was stirred
for 30 min. The reaction mixture after column chromato-
graphy afforded a product 3a in 10% yield (Scheme 1).
1
DCM
DCM
DCM
DCM
DCE
rt
0.5
0.5
0.5
0.5
0.5
1
10
2
PPh3 (5 mol %)
PPh3
rt
trace
5
3
50
0 to rt
rt
4
PPh3
8
5
PPh3
5
6
CHCl3 PPh3
rt
trace
7
DCM
DCM
DCM
DCM
DCM
DCM
THF
PMe3
rt
12
0.5
24
8
PBu3
rt
25
Scheme 1. Reaction of Ethyl Penta-2,3-dienoate with Benzil
9
P(2-CH3C6H4)3
TDMPPa
P(Cy)3
rt
10
11
12
13
14
rt
4
4
45
33
rt
P(C6F5)3
TDMPPa
toluene TDMPPa
rt
24
3
rt
94
20
rt
16
a TDMPP = tris(2,6-dimethoxyphenyl)phosphine.
The product was characterized using conventional
spectroscopic methods, and conclusive evidence for its
Subsequent investigations revealed that the reaction was
general with respect to different acyclic 1,2-diones and
allenoates, and the results are summarized as follows
(Table 2).
(6) For reviews, see: (a) Ye, L.-W.; Zhou, J.; Tang, Y. Chem. Soc.
Rev. 2008, 37, 1140. (b) Yu, S.; Ma, S. Angew. Chem., Int. Ed. 2012, 51, 2.
(c) Zhao, Q.-Y.; Lian, Z.; Wei, Y.; Shi, M. Chem. Commun. 2012, 48,
1724. (d) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009, 38, 3102. (e)
Ma, S. Chem. Rev. 2005, 105, 2829. (f) Methot, J. L.; Roush, W. R. Adv.
Synth. Catal. 2004, 346, 1035. (g) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem.
Res. 2001, 34, 535.
(7) For selected recent reports, see: (a) Xiao, H.; Chai, Z.; Cao, D.;
Wang, H.; Chen, J.; Zhao, G. Org. Biomol. Chem. 2012, 10, 3195. (b)
Chen, X.-Y.; Lin, R.-C.; Ye, S. Chem. Commun. 2012, 48, 1317. (c) Chen,
X.-Y.; Ye, S. Eur. J. Org. Chem. 2012, 5723. (d) Steurer, M.; Jensen,
K. L.; Worgull, D.; Jørgensen, K. A. Chem.;Eur. J. 2012, 18, 76. (e)
Wang, D.; Wei, Y.; Shi, M. Chem. Commun. 2012, 48, 2764. (f) Wang,
Y.; Yu, Z.-H.; Zheng, H.-F.; Shi, D.-Q. Org. Biomol. Chem. 2012, 10,
7739. (g) Na, R.; Jing, C.; Xu, Q.; Jiang, H.; Wu, X.; Shi, J.; Zhong, J.;
Wang, M.; Benitez, D.; Tkatchouk, E.; Goddard, W. A., III; Guo, H.;
Kwon, O. J. Am. Chem. Soc. 2011, 133, 13337. (h) Wang, T.; Ye, S. Org.
Biomol. Chem. 2011, 9, 5260. (i) Szeto, J.; Sriramurthy, V.; Kwon, O.
Org. Lett. 2011, 13, 5420. (j) Fujiwara, Y.; Fu, G. C. J. Am. Chem. Soc.
2011, 133, 12293.
(8) (a) Nair, V.; Paul, R. R.; Suresh, E. Synthesis 2010, 3741. (b) Nair,
V.; Vidya, N.; Abhilash, K. G. Org. Biomol. Chem. 2008, 6, 1738. (c)
Nair, V.; Pillai, A. N.; Suresh, C. H. Chem.;Eur. J. 2008, 14, 5851. (d)
Nair, V.; Biju, A. T.; Abhilash, K. G.; Menon, R. S.; Suresh, E. Org.
Lett. 2005, 7, 2121. (e) Nair, V.; Pillai, A. N.; Menon, R. S.; Suresh, E.
Org. Lett. 2005, 7, 1189.
(9) (a) Zhu, X.-F.; Henry, C. E.; Wang, J.; Dudding, T.; Kwon, O.
Org. Lett. 2005, 7, 1387. (b) Zhu, X.-F.; Schaffner, A.-P.; Li, C. R.;
Kwon, O. Org. Lett. 2005, 7, 2977. (c) Ma, R.; Xu, S.; Tang, X.; Wu, G.;
He, Z. Tetrahedron 2011, 67, 1053. (d) Xu, S.; Zhou, L.; Ma, R.; Song,
H.; He, Z. Org. Lett. 2010, 12, 544. (e) Xu, S.; Zhou, L.; Zeng, S.; Ma, R.;
Wang, Z.; He, Z. Org. Lett. 2009, 11, 3498. (f) Xu, S.; Zhou, L.; Ma, R.;
Song, H.; He, Z. Chem.;Eur. J. 2009, 15, 8698.
The reaction appears to be working well with unsym-
metrical diaryl 1,2-diones, and an example using 1-(4-
bromophenyl)-2-phenylethane-1,2-dione is shown in
Scheme 2. However, as expected, the reaction yielded
two regioisomers as inseparable mixture in 1:0.88 ratio.
The reaction may be rationalized by the following
mechanistic postulate (Scheme 3). Conceivably, the first
step is the nucleophilic addition of triarylphosphine to
allene ester resulting in the formation of a 1,3-dipolar
zwitterion. The latter then attacks a carbonyl group of
the dione forming C. This species loses a molecule of water
to afford a cationic intermediate D. Addition of water to
the latter followed by cyclization and elimination of phos-
phine delivers 3a.
Our subsequent studies showed that the reaction
afforded 2-alkylidenetetrahydrofuran11 as the major prod-
uct, when triphenylphosphine was used as the catalyst
with THF as solvent at room temperature. When the
(10) It may be noted that the reaction proceeded smoothly when a
stoichiometric amount of phosphine was used. The catalytic reaction is
very slow, and it suffers from side reactions.
Org. Lett., Vol. 15, No. 8, 2013
1859

Table 2. Substrate Scope
Scheme 3. Proposed Mechanism
entry
Ar
R1
R2
product yield (%)
1
phenyl
ÀCH3 ÀC2H5
ÀCH3 ÀC2H5
ÀCH3 ÀC2H5
ÀCH3 ÀC2H5
ÀCH3 ÀC2H5
3a
3b
3c
3d
3e
3f
94
96
93
90
92
88
81
65
93
81
92
94
82
83
78
2
4-fluorophenyl
4-chlorophenyl
4-bromophenyl
4-methylphenyl
3
4
5
6
4-methoxyphenyl ÀCH3 ÀC2H5
7
2-thienyl
ÀCH3 ÀC2H5
ÀCH3 ÀC2H5
ÀCH3 ÀC2H5
ÀC6H5 ÀC2H5
ÀC6H5 ÀC2H5
ÀC6H5 ÀC2H5
ÀCH3 ÀC(CH3)3
ÀCH3 ÀC(CH3)3
ÀCH3 ÀC(CH3)3
3g
3h
3i
8
2-furoyl
9
naphthyl
10
11
12
13
14
15
phenyl
3j
4-methylphenyl
4-fluorophenyl
phenyl
3k
3l
3m
3n
3o
4-fluorophenyl
4-methylphenyl
Scheme 4
representative 1,2-diones and ethyl penta 2,3-dienoate
are given in Scheme 4.
Figure 1. ORTEP diagram of 3b.
Interestingly, the reaction with ethyl pyruvate under the
same condition afforded 2-alkylidenetetrahydrofuran de-
rivative exclusively (Scheme 5).
Scheme 2. Reaction of Ethyl Penta-2,3-dienoate with
1-(4-Bromophenyl)-2-phenylethane-1,2-dione
Scheme 5
In conclusion, we have encountered a novel annulation of
allenoateÀphosphine zwitterion with acyclic 1,2-diones re-
sulting in the formation of substituted cyclopentenone
reaction was conducted in solvents such as toluene, diox-
ane, or xylene, the same product was obtained in low yield.
In this context, it may be recalled that He and co-
workers have reported the annulation of phosphine-
γ-alkyl allenoate zwitterion to aldehydes to afford
2-alkylidenetetrahydrofurans.9f A few examples using
(11) The E geometry of the double bond in 2-alkylidenetetrahydro-
furans was ascertained by comparing the chemical shift values of
analogous compounds reported.9f Further support for the assignment
was accrued by NOE studies of compound 6d.
1860
Org. Lett., Vol. 15, No. 8, 2013

derivatives. It is noteworthy that 4-hydroxycyclopentene-
1-ones are of pharmacological importance and are em-
bedded in natural products such as prostaglandins.12 In
addition, a number of natural and synthetic 4-hydroxy
cyclopentene-1-ones are useful crop protection agents.12c,13
It may also be mentioned that cyclopentenones have found
use in the construction of polysubstituted aromatic hydro-
carbons,14 isotruxenones,15 and diquinanes.16
€
(12) Forreviewsonprostaglandins, see:(a)Pace-Asciak, C.;Granstrom,
E. Prostaglandins and Related Substances; Elsevier: New York, 1983. (b)
Nicolaou, A.; Kokotos, G. Prostanoids. In Bioactive Lipids; Oily Press:
Bridgwater, 2004; p 197. (c) Ro€mpp Lexikon Naturstoffe; Fugmann, B.,
Lane-Fugmann, S., Steglich, W., Eds.; Thieme: Stuttgart, 1997. (d) Bindra,
J. S. The Synthesis of Prostaglandins. In Total Synthesis of Natural
Products; ApSimon, J., Ed.; John Wiley & Sons, Inc.: Hoboken, 2007;
Vol. 4, Chapter 4.
Acknowledgment. We thank the Department of Science
and Technology (DST), New Delhi, for Raja Ramanna
Fellowship. We also thank the Council of Scientific and
Industrial Research (CSIR), New Delhi, for financial
assistance.
(13) (a) Molecular Action of Insecticides on Ion Channels; American
Chemical Society: Washington, DC, 1995; ACS Syp. Ser. 591, p 2643. (b)
Handbookof Pesticide Toxicology; Hayes, W. J., Ed.; AcademicPress: New
York, 1991; p 585.
Supporting Information Available. Experimental pro-
cedures and compound characterization data. This ma-
terial is available free of charge via the Internet at http://
pubs.acs.org.
€
(14) Holtz, E.; Kohler, V.; Appel, B.; Langer, P. Eur. J. Org. Chem.
2005, 532.
(15) Yang, J.-S.; Huang, H.-H.; Lin, S.-H. J. Org. Chem. 2009, 74,
3974.
(16) Romero, J. M. L.; Sapmaz, S.; Fensterbank, L.; Malacria, M.
Eur. J. Org. Chem. 2001, 767.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 8, 2013
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