Reverse of regioselectivity in intramolecular nucleophilic substitution of π-allyl palladium species. Highly selective formation of vinylic cyclopropanes via the pd(0)-catalyzed coupling-cyclization reaction of organic iodides with 2-(2′,3′-dienyl)malonates

Article abstract of DOI:10.1021/ol006165u

(formula presented) Vinylic cyclopropanes were formed highly selectively via the Pd(PPh₃)₄-catalyzed insertion-intramolecular nucleophilic substitution reaction of aryl or 1-alkenyl iodides with 2-(2′,3′-dienyl)malonates. The regioselectivity observed here is different from what was reported by Cazes et al.

Full text of DOI:10.1021/ol006165u

ORGANIC
LETTERS
2000
Vol. 2, No. 16
2495-2497
Reverse of Regioselectivity in
Intramolecular Nucleophilic Substitution
of π-Allyl Palladium Species. Highly
Selective Formation of Vinylic
Cyclopropanes via the Pd(0)-Catalyzed
Coupling−Cyclization Reaction of
Organic Iodides with
2-(2′,3′-Dienyl)malonates
Shengming Ma* and Shimin Zhao
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. China
masm@pub.sioc.ac.cn
Received June 8, 2000
ABSTRACT
Vinylic cyclopropanes were formed highly selectively via the Pd(PPh3)4-catalyzed insertion−intramolecular nucleophilic substitution reaction
of aryl or 1-alkenyl iodides with 2-(2′,3′-dienyl)malonates. The regioselectivity observed here is different from what was reported by Cazes et
al.
Allenes are a class of compounds with unique reactivity and
chirality when properly substituted.1 Recently much attention
has been paid to the chemistry of allenes.2 Among our efforts
toward transition metal-catalyzed chemistry of allenes,3 we
observed the exclusive formation of five-membered buteno-
lides and furans from 2,3-dienoic acids4 and 1,2-dienyl
ketones,5 respectively. Interestingly, the Pd(0)-catalyzed
coupling-cyclization reaction of 2,3-dienols and organic
halides afforded three-membered vinylic oxiranes; the forma-
tion of the corresponding 2,5-dihydrofurans was not ob-
served, implying that the intramolecular nucleophilic sub-
stitution of the π-allyl palladium occurred regiospecifically
via path a (Scheme 1).6
Cazes et al. studied the Pd(0)-catalyzed coupling cycliza-
tion reaction of 2-(2′,3′-dienyl)malonates with organic
halides.7 In most cases the five-membered cyclopentene
derivatives were formed as the major products. The regio-
(3) For some examples of Pd-catalyzed reactions see: (a) Shimizu, I.;
Tsuji, J. Chem. Lett. 1984, 233. Ahmar, M.; Cazes, B.; Gore, J. Tetrahedron
Lett. 1984, 25, 4505. (b) Larock, R. C.; Berrios-Pena, N. G.; Fried, C. A.
J. Org. Chem. 1991, 56, 2615. (c) Larock, R. C.; Zenner, J. M. J. Org.
Chem. 1995, 60, 482. (d) Okuro, K.; Alper, H. J. Org. Chem. 1997, 62,
1566. (e) Walkup, R. D.; Guan, L.; Mosher, M. D.; Kim, S. W.; Kim, Y.
S. Synlett 1993, 88. (f) Ohno, H.; Toda, A.; Miwa, Y.; Taga, T.; Osawa,
E.; Yamaoka, Y.; Fujii, N.; Ibuka, T. J. Org. Chem. 1999, 64, 2992. (g)
Ma, S.; Negishi, E. J. Org. Chem. 1994, 59, 4730. (h) Grigg, R.; Xu, L.
Tetrahedron Lett. 1996, 37, 4251. (i) Nemoto, H,; Yoshida, M.; Fukumoto,
K. J. Org. Chem. 1997, 62, 6450. Jeong, I.;-Y.; Nagao, Y. Tetrahedron
Lett. 1998, 39, 8677. (j) Grigg, R.; Rasul, R.; Redpath, J.; Wilson, D.
Tetrahedron Lett. 1996, 37, 4609. Oppolzer, W.; Pimm, A.; Stammen, B.;
Hume, W. E. HelV. Chim. Acta 1997, 80, 623.
(1) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; John
Wiley & Sons: New York, 1988. The Chemistry of Ketenes, Allenes, and
Related Compounds, Part 1; Patai, S., Ed.; John Wiley & Sons: New York,
1980.
(2) (a) Hashmi, A. S. K. Angew. Chem., Int. Ed. Engl. 1995, 34, 1581-
1583. (b) Ma, S.; Shi, Z.; Yu, Z. Tetrahedron Lett. 1999, 40, 2393-2396.
Ma, S.; Shi, Z.; Yu, Z. Tetrahedron 1999, 55, 12137-12148.
10.1021/ol006165u CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/14/2000

the formation of cyclopropane derivative 3a together with
cyclopentene derivative 4a (entries 1 and 2, Scheme 3).
Scheme 1
Scheme 3
selectivity is opposite to that of our results with 2,3-allenols6
and consistent with that observed with 2,3-allenoic acids4
and 1,2-allenyl ketones.5 The only case reported for the
exclusive formation of 1,5-(bismethoxylcarbonyl)-2-vinyl
cyclopropane was the Pd(0)-catalyzed reaction of vinyl
bromide with 2-(2′,3′-dienyl)malonates (Scheme 2).7a,b In this
However, this reaction did occur in toluene, benzene, or
CH3CN to afford 1,1-(bismethoxycarbonyl)-2-(1′-phenyl)-
ethenyl cyclopropane 3a exclusively, albeit in low yield (30-
41%) (entries 3-6, Scheme 3), indicating a nice solvent
effect on the regioselectivity of this reaction. Luckily, after
some trial and error, we found that the addition of a catalytic
amount of n-Bu4NBr as the phase transfer catalyst improved
the yield of 3a dramatically, and the formation of the five-
membered product, i.e., 1-phenyl-4,4-(bismethoxycarbonyl)-
cyclopentene 4a, was not observed (entry 7, Scheme 3). The
addition of a catalytic amount of the phase transfer catalyst,
i.e., TBAB, may facilitate oxidative addition, carbopallada-
tion of allene, and the intramolecular nucleophilic substitution
reaction while it did not change the regioselectivity of this
transformation.8 For the reaction with phenyl bromide, the
yields were lower; however, the effect of TBAB was still
obvious (compare entries 8 and 9, Scheme 3).
Scheme 2
With this optimized reaction conditions in hand, we studied
the Pd(PPh3)4-catalyzed reaction of aryl halides/1-alkenyl
paper we wish to report our own results on the Pd(0)-
catalyzed reaction of 2-(2′,3′-dienyl)malonates with organic
halides, in which a completely different regioselectivity was
observed.
Table 1. Pd(PPh3)4-Catalyzed Cyclization of Methyl
2-(2′,3′-Butadienyl)malonate with Organic Iodides
When we carried out the reaction of dimethyl 2-(2′, 3′-
butadienyl)malonate 1 with PhI under the conditions de-
scribed in ref 6, i.e., Pd(PPh3)4 as the catalyst, K2CO3 as the
base, and DMF (or DMSO) as the solvent, we did observe
(4) (a) For the Pd(0)/Ag+-cocatalyzed cyclization of organic halides with
1,2-allenyl carboxylic acids to afford butenolides, see: Ma, S.; Shi, Z. J.
Org. Chem. 1998, 63, 6387-6389. Ma, S.; Duan, D.; Shi, Z. Org. Lett.
2000, 2, 1419. (b) For CuX2 (X ) Br, Cl)-mediated cyclization of 1,2-
allenyl carboxylic acids to afford â-halobutenolides, see: Ma, S.; Wu, S.
J. Org. Chem. 1999, 64, 9314.
(5) Ma, S.; Zhang, J. Chem. Commun. 2000, 117-118. Ma, S.; Li, L.
Org. Lett. 2000, 2, 941.
(6) Ma, S.; Zhao, S. J. Am. Chem. Soc. 1999, 121, 7943.
(7) (a) Ahmar, M.; Cazes, B.; Gore, J. Tetrahedron Lett. 1985, 26, 3795.
(b) Ahmar, M.; Cazes, B.; Gore, J. Tetrahedron 1987, 43, 3453. (c) Besson,
L.; Bazin, J.; Gore, J.; Cazes. B. Tetrahedron Lett. 1994, 35, 2881. (d)
Gamez, P.; Ariente, C.; Gore, J.; Cazes, B. Tetrahedron 1998, 54, 14835.
entry
R (2)
time (h) yield (%) of 3
1
2
3
4
5
6
7
8
Ph (2a )
15
16
17
24
24
16
17
23
80 (3a )
67 (3b)
69 (3c)
82 (3d )
58 (3e)
46 (3f)
83 (3g)
86 (3h )
(E)-1-hexenyl (2b)
p-methoxyphenyl (2c)
p-methylphenyl (2d )
p-methoxycarbonylphenyl (2e)
(E)-1-(2′-phenyl)ethenyl (2f)
p-bromophenyl (2g)
naphthyl (2h )
2496
Org. Lett., Vol. 2, No. 16, 2000

halides with 2-(2′,3′-butadienyl)malonate; the results are
summarized in Table 1. It should be pointed out that for all
entries in Table 1 only the vinylic cyclopropane derivatives
were formed, aryl iodides with both an electron-donating or
electron-withdrawing group can be used (entries 3-5), the
reaction afforded 1,3-dienyl cyclopropanes when 1-alkenyl
iodides were used (entries 2 and 6), and with p-bromophenyl
iodide, only the carbon-iodine bond participated in the
oxidative addition reaction while the carbon-bromine re-
mained intact (entry 7).
In conclusion, we have developed an efficient synthesis
of vinylic cyclopropane derivatives. It is obvious that the
selectivity is high and different from that observed by Cazes
et al.7 The relative stability of the intermediates A and B in
the reaction process determined the regioselectivity of this
reaction, indicating the exclusive formation of a B-type
intermediate for the reactions shown in Table 1. Further
studies on the scope and mechanism, especially the factor
controlling the regioselectivity, of this reaction are underway
in our laboratory.
The reaction of methyl 2-(2′,3′-heptadienyl)malonate with
PhI under the same reaction conditions afforded a mixture
of three-membered and five-membered products with the
three-membered product 3i predominating (eq 1).
Acknowledgment. Financial support from Chinese Acad-
emy of Sciences and the Major State Basic Research
Development Program (Grant G2000077500) are greatly
appreciated. Shengming Ma is the recipient of a 1999 Qiu
Shi Award for Young Scientific Workers issued by the Hong
Kong Qiu Shi Foundation of Science and Technology
(1999-2002) and a Special Starting Grant for Outstanding
Young Chemists issued by the National Science Foundation
of China (29525202).
However, the unique regioselectivity seems to be limited
to maolonate derivatives. The reaction of 2-(2′,3′-butadienyl)-
malonitrile with PhI afforded the cyclopentene derivative 4j
as the sole product (eq 2).
Supporting Information Available: Typical experimen-
tal procedure and analytical data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(8) Jeffery, T. Synthesis 1987, 70. Jeffery, T. Tetrahedron Lett. 1985,
26, 2667. Jeffery, T. J. Chem. Soc., Chem. Commun. 1984, 1287.
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