Stannylative cycloaddition of enynes catalyzed by palladium-iminophosphine

Article abstract of DOI:10.1021/ja044429s

Palladium-iminophosphine complex catalyzes stannylative cycloaddition of conjugated enynes using hexabutyldistannoxane as a stannylating agent to afford highly substituted 3-alkenylphenylstannanes regioselectively. Stannylative cross-cycloaddition reactio

Full text of DOI:10.1021/ja044429s

Published on Web 11/11/2004
Stannylative Cycloaddition of Enynes Catalyzed by
Palladium-Iminophosphine
Yoshiaki Nakao,*,† Yasuhiro Hirata,† Shinjiro Ishihara,† Shinichi Oda,† Tomoya Yukawa,†
Eiji Shirakawa,*,‡ and Tamejiro Hiyama*,†
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity, Kyoto 615-8510 Japan, and
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Kyoto 606-8502 Japan
Received September 14, 2004; E-mail: nakao@npc05.kuic.kyoto-u.ac.jp; shirakawa@kuchem.kyoto-u.ac.jp; thiyama@npc05.kuic.kyoto-u.ac.jp
Transition metal-catalyzed regioselective cycloaddition reaction
of unsaturated compounds is a powerful tool for one-step construc-
tion of substituted benzene.1 Metalative versions of the reaction
would broaden its synthetic versatility as the resulting aromatic
organometallics should enjoy a variety of transformations. However,
such a reaction has been limited to titanative cyclotrimerization of
alkynes.2 Although the reaction provides variously substituted
phenyl- and benzyltitanium compounds with perfect chemo- and
regioselectivities, it involves multistep procedures and requires a
leaving group, such as sulfonyl or bromo, in an alkyne molecule.
Herein, we report the regioselective stannylative cycloaddition of
conjugated enynes catalyzed by a palladium complex having N-(2-
diphenylphosphinobenzylidene)cyclohexylamine (1) as a ligand to
and typical ligands, such as PPh3 and dppp, or ligandless conditions
give variously substituted 3-alkenylphenylstannanes 3 (eq 1). The
retarded the reaction.11,12
synthetic potential of the reaction is successfully demonstrated by
With the optimized conditions in hand, we studied the scope of
a concise synthesis of alcyopterosin N, which has been isolated
the reaction and found that a wide variety of functional groups
tolerated the reaction conditions (Table 1). Thus, 2-substituted
recently from sub-Antarctic soft coral, Alcyonium paessleri.3,4 The
nonstannylative version of the present reaction has been studied
extensively by Yamamoto and co-workers.5,6
Table 1. Stannylative Cycloaddition of Enynes Catalyzed by
Pd-1a
entry
enyne
products
yield of 3 (%)b
yield of 4 (%)c
1
2
3
4
5
2b
2c
2d
2e
2f
2g
2h
2i
3b, 4b
3c, 4c
3d, 4d
3e, 4e
3f, 4f
3g, 4g
3h, 4h
3i, 4i
65
71
64
52
65
67
71
67
66
67
20
23 (26)d
22
12
27
6
<5e
7f
8f
9f
10f
4d
20
10
30
2j
2k
3j, 4j
3k, 4k
During our investigation of the alkynylstannylation of 2-methyl-
1-buten-3-yne (2a) with tributyl(phenylethynyl)tin using a Pd-1
catalyst,7 we obtained unexpectedly 2-methyl-5-(propen-2-yl)-1-
(tributylstannyl)benzene (3a) in 57% yield, as estimated by 119Sn
NMR analysis of the crude products (eq 2).8 None of the expected
alkynylstannylation products or the regioisomers of 3a were
detected. GC analysis of the products showed the coproduction of
nonstannylated product 4a in 11% yield.9 As the phenylethynyl
moiety in the stannane reagent was lost, we surveyed various
stannane donors10 to find that hexabutyldistannoxane was the
optimum to give 3a in 74% yield by 119Sn NMR. It is worthy to
note that both of the stannyl groups in the stannoxane participate
in the reaction. We further optimized reaction conditions and found
that a combination of (η5-cylcopentadienyl)(η3-allyl)palladium [Cp-
(allyl)Pd], 1, and maleic anhydride (1:1:1.5, 5 mol % Pd, with
respect to the Bu3Sn group) was the best to give 3a in 81% isolated
yield. The use of the other derivatives of 1 gave inferior results,
a The reaction was carried out using an enyne (0.90 mmol), (Bu3Sn)2O
(0.15 mmol), Cp(allyl)Pd (15 µmol), 1 (15 µmol), and maleic anhydride
(23 µmol) in THF at 50 °C for 24 h. b Isolated yields based on the Bu3Sn
group. c Isolated yields based on the enyne. d Determined by GC based on
the enyne. e Determined by 1H NMR. f The reaction was carried out using
60 µmol of Pd-1 catalyst and 90 µmol of maleic anhydride at 80 °C.
1-buten-3-ynes (2b-2f) having an alkenyl, alkynyl, or siloxy group
reacted to give arylstannanes 3b-3f in good yields (entries 1-5).
Ethyl (Z)-2-penten-3-ynoate (2g) also gave the corresponding
arylstannane 3g in 67% yield, together with only a trace amount
of nonstannylated product 4g (entry 6). Enynes having an internal
triple bond and a methoxy or cyano group underwent the reaction
under conditions that employed more catalyst (20 mol %) at 80
°C, and various 2,6-disubstituted 3-stannylstyrenes were produced
in good yields (entries 7-10). However, 1,2- and 2,4-disubstituted
1-buten-3-ynes, such as 1-ethynylcyclohexene and 2-methyl-1-
decen-4-yne, failed to give the corresponding products.
The reaction was also applicable to cross-cycloaddition reactions
between different enynes or between enynes and diynes.13 For
† Graduate School of Engineering.
‡ Graduate School of Science.
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15650
J. AM. CHEM. SOC. 2004, 126, 15650-15651
10.1021/ja044429s CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Stannylative Cross-Cycloaddition of Enynes
Supporting Information Available: Detailed experimental pro-
cedures, including spectroscopic and analytical data. This material is
available free of charge via the Internet at http:/pubs.acs.org.
References
(1) Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901-2915.
(2) (a) Suzuki, D.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 2001, 123, 7925-
7926. (b) Tanaka, R.; Nakano, Y.; Suzuki, D.; Urabe, H.; Sato, F. J. Am.
Chem. Soc. 2002, 124, 9682-9683.
(3) Palermo, J. A.; Rodr´ıguez Brasco, M. F.; Spagnuolo, C.; Seldes, A. M. J.
Org. Chem. 2000, 65, 4482-4486.
(4) For total synthesis of other families of alcyopterosins, see: Witulski, B.;
Zimmermann, A.; Gowans, N. D. Chem. Commun. 2002, 2984-2985,
and ref 2b.
(5) (a) Saito, S.; Salter, M. M.; Gevorgyan, V.; Tsuboya, N.; Tando, K.;
Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 3970-3971. (b) Gevorgyan,
V.; Tando, K.; Uchiyama, N.; Yamamoto, Y. J. Org. Chem. 1998, 63,
7022-7025. (c) Gevorgyan, V.; Takeda, A.; Homma, M.; Sadayori, N.;
Radhakrishnan, U.; Yamamoto, Y. J. Am. Chem. Soc. 1999, 121, 6391-
6402. (d) Saito, S.; Chounan, Y.; Nogami, T.; Fukushi, T.; Tsuboya, N.;
Yamada, Y.; Kitahara, H.; Yamamoto, Y. J. Org. Chem. 2000, 65, 5350-
5354. (e) Saito, S.; Ohmori, O.; Yamamoto, Y. Org. Lett. 2000, 2, 3853-
3855. (f) Saito, S.; Tando, K.; Kabuto, C.; Yamamoto, Y. Organometallics
2000, 19, 3740-3743. (g) Gevorgyan, V.; Yamamoto, Y. J. Organomet.
Chem. 1999, 576, 232-247. (h) Saito, S.; Yamamoto, Y. J. Synth. Org.
Chem. 2001, 59, 346-354. (i) Rubin, M.; Sromek, A. W.; Gevorgyan,
V. Synlett 2003, 2265-2291 and references therein.
1
a Isolated yields based on the Bu3Sn group. b Determined by H NMR
based on 2a. c Determined by 119Sn NMR based on the Bu3Sn group.
d Determined by GC based on 2a.
Scheme 2. Synthesis of Alcyopterosin Na
(6) For thermal or Lewis acid-mediated intramolecular [4 + 2] cycloadditions
of enynes with alkynes, see: (a) Danheiser, R. L.; Gould, A. E.; Ferna´ndez
de la Pradilla, R.; Helgason, A. L. J. Org. Chem. 1994, 59, 5514-5515.
(b) Burrell, R. C.; Daoust, K. J.; Bradley, A. Z.; DiRico, K. J.; Johnson,
R. P. J. Am. Chem. Soc. 1996, 118, 4218-4219.
(7) (a) Shirakawa, E.; Yoshida, H.; Kurahashi, T.; Nakao, Y.; Hiyama, T. J.
Am. Chem. Soc. 1998, 120, 2975-2976. (b) Yoshida, H.; Shirakawa, E.;
Kurahashi, T.; Nakao, Y.; Hiyama, T. Organometallics 2000, 19, 5671-
5678. For an account of the carbostannylation, see: (c) Shirakawa, E.;
Hiyama, T. Bull. Chem. Soc. Jpn. 2002, 75, 1435-1450.
(8) The structure of the products was determined unambiguously by a
combination of NOE experiments, JH-H and JH-Sn values, and protod-
estannylation. For details, see Supporting Information.
(9) Under the reaction conditions, 4a and hexabutylstannoxane did not give
3a.
(10) For detailed results, see Supporting Information.
(11) As the reaction generates water, we also examined the effect of molecular
sieves 4A (100 mg) under the optimized conditions and found that the
yield of 3a was unchanged (81% by 119Sn NMR), whereas that of 4a was
slightly lowered (8% by GC). On the other hand, addition of water (3.0
equiv with respect to the Bu3Sn group) to the reaction mixture diminished
the yield of 3a (43% by 119Sn NMR) and increased that of 4a (25% by
GC). Thus, the formation of 4a might be derived partially from hydrolysis
of 3a and/or 12 (see ref 16).
(12) Use of [(η3-allyl)PdCl]2 or Pd2(dba)3 for the reaction of enynes 2b-f
caused isomerization of the alkenyl moieties of 3b-f. For detailed results,
see Supporting Information. Maleic anhydride might affect the rapid
reductive elimination of Cp and allyl from Cp(allyl)Pd due presumably
to its strong π-accepting character, generating active Pd(0)-1 effectively.
For the acceleration of reductive elimination by maleic anhydride, see:
Yamamoto, T.; Yamamoto, A.; Ikeda, S. J. Am. Chem. Soc. 1971, 93,
3350-3359.
a Reagents and Conditions: (a) BrCH2CH(CO2Me)dCH2 (1.1 equiv),
Pd2(dba)3 (5 mol %), PPh3 (20 mol %), NMP, 100 °C, 3 h; (b) DIBAL-H
(3.0 equiv), CuMe (10 mol %), THF-HMPA, -50 °C, 1 h, then MeI (20
equiv), -10 °C, 25 h; (c) Me2CHCMe2BH2 (5.0 equiv), THF, 0 °C, 3 h,
then H2O2, NaOH aq., rt, 3 h; (d) LiOH (10 equiv), H2O-MeOH (9:1), 50
°C, 12 h; (e) Ac2O (10 equiv), pyridine (5.0 equiv), CH2Cl2, rt, 9 h; (f)
SOCl2 (10 equiv), CH2Cl2, rt to 40 °C, 4 h, then AlCl3 (1.2 equiv), CH2Cl2,
40 °C, 3 h; (g) K2CO3 (5.0 equiv), H2O-MeOH (1:1), rt, 1 h.
example, the reaction of 2a with ethyl (Z)-2-undecen-4-ynoate or
1,4-diphenylbutadiyne under similar conditions14 afforded the
corresponding arylstannane 5 or 6, respectively, in good yield
(Scheme 1).
The synthetic potential of the reaction is demonstrated by
synthesis of alcyopterosin N starting with 2,6-dimethyl-3-(tributyl-
stannyl)styrene (3h) (Scheme 2). Thus, Pd-catalyzed cross-coupling
reaction of 3h with ethyl R-bromomethylacrylate gave 7 in 87%
yield. Copper-catalyzed 1,4-reduction15 of 7 followed by R-meth-
ylation yielded 8, which was subjected to hydroboration-oxidation
sequence to provide the alcohol 9. Acetylation of the hydroxyl group
in 9 was followed by the intramolecular Friedel-Clafts acylation
and deacetylation to give alcyopterosin N.
(13) For nonstannylative versions of the intermolecular cross-cycloadditions,
see ref 5c,e and refs cited in 5g-i.
(14) Although the reason remains yet to be clarified, a catalyst derived from
a 1:1 molar ratio of Pd and 1 gave slightly lower yields of 5 (74%) and
6 (67%), as estimated by 119Sn NMR. Maleic anhydride is not essential
in these cases.
In conclusion, we have demonstrated regioselective stannylative
cycloaddition of enynes catalyzed by Pd-1. Highly substituted
3-alkenylphenylstannanes obtained by this reaction are demonstrated
to be synthetically useful by the concise synthesis of alcyopterosin
N. Efforts directed toward expansion of the reaction scope and
elaboration of the detailed mechanism16 are currently underway in
our laboratories.
(15) Tsuda, T.; Hayashi, T.; Satomi, H.; Kawamoto, T.; Saegusa, T. J. Org.
Chem. 1986, 51, 537-540.
(16) The mechanism of the present reaction is totally unclear at the present
stage. A referee suggests a mechanism involving interception of a strained
cyclic allene intermediate 12, which is formed via 11 (see ref 5c), with
the Bu3Sn group to give a stannylated product 3. Analogous reactions of
a strained allene intermediate with a chlorine radical or proton has been
reported: Rodr´ıguez, D.; Navarro-Va´zquez, A.; Castedo, L.; Dom´ınguez,
D.; Saa´, C. J. Org. Chem. 2003, 68, 1938-1946, and ref 6a.
Acknowledgment. The authors acknowledge Professor Koichiro
Oshima for allowing us to use 500 MHz NMR. This work has been
supported financially by Grant-in-Aids for Creative Scientific
Research (16GS0209), COE Research on “Elements Science” and
on “United Approach to New Material Science”, and Encourage-
ment for Young Scientists (B) from MEXT. Y.N. also thanks The
Japan Science Society for the Sasakawa Scientific Research Grant.
JA044429S
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