Carbocycle synthesis through facile and efficient palladium-catalyzed allylative de-aromatization of naphthalene and phenanthrene allyl chlorides

Article abstract of DOI:10.1002/anie.200800529

(Chemical Equation Presented) Ring of truth: The palladium-catalyzed reaction of allyltributylstannane with naphthalene or phenanthrene derivatives bearing an allyl chloride group proceeds smoothly to provide de-aromatized products with unique structures

Full text of DOI:10.1002/anie.200800529

Communications
DOI: 10.1002/anie.200800529
Synthetic Methods
Carbocycle Synthesis through Facile and Efficient Palladium-Catalyzed
Allylative De-aromatization of Naphthalene and Phenanthrene Allyl
Chlorides**
Shirong Lu, Zhanwei Xu, Ming Bao,* and Yoshinori Yamamoto*
De-aromatization reactions of arenes have attracted consid-
erable attention because they provide a simple way to
synthesize functionalized alicyclic compounds, which can be
used as intermediates for the preparation of natural products
and bioactive compounds.[1] Over the past four decades, many
methods, including oxidation,[2] reduction,[3] photocycloaddi-
tion,[4] [2,3] s-rearrangement,[5] electrophilic addition,[6]
nucleophilic addition,[7] and other approaches[8] have been
developed for breaking up the conjugated p system. The
complexation of aromatic system to transition metals leads to
the activation of arenes and thus facilitates the electrophilic
addition of [M(h2-arene)] (M = Os, Re, Mo, and W) com-
plexes and the nucleophilic addition of [M(h6-arene)] (M =
Cr, Mn, and Ru) complexes.
intermediate 5, generated from the cinnamyl chlorides and
allyltributyltin in the presence of a palladium catalyst, could
undergo rearrangement to give the h3-benzylpalladium inter-
mediate 5’, and 6’ (or its para isomer) would be produced.
However, only the Stille cross-coupling product 6 was
obtained [Eq. (2)].[10] Thus, extension of the de-aromatization
to the cinnamyl chlorides 4 was not feasible.
We recently reported the facile palladium-catalyzed
allylative de-aromatization reaction of benzylic chlorides 1
with allyltributytin.[9] This process appears to involve the
formation and isomerization of the h3-allyl-h3-benzylpalla-
dium intermediate 2 to give 2’, which led to 3, where an allyl
group is linked para to the exocyclic methylene group
[Eq. (1)]. Our interest in extending the scope of this de-
Herein, we report the facile and efficient allylative de-
aromatization of naphthalene and phenanthrene derivatives
bearing an allyl chloride unit (Tables 1 and 2). These reactions
did not form the corresponding Stille cross-coupling products,
but pleasingly gave the ortho allylated product 8; this
regioselectivity is in marked contrast to the para selectivity
of the de-aromatization of benzylic chlorides. This result
introduces the possibility of synthesizing six-membered ring
systems with three or four fused rings from naphthalenes or
phenanthrenes, respectively.
The allylative de-aromatization reactions of naphthalene
derivatives 7a–i with allyltributylstannane were performed in
the presence of [Pd2(dba)3] (5 mol%) and PPh3 (20 mol%;
Table 1). The simple substrates 7a and 7h underwent the de-
aromatization reaction smoothly to afford 8a and 8h in high
yields (84% and 78%, respectively; Table 1, entries 1 and 8).
Neither the electron-donating group nor the electron-with-
drawing group on the aromatic ring exerted a strong influence
on the reaction (except in terms of the reaction times). The
yields of 8b–g and 8i were in the range of 74 to 89% (Table 1,
entries 2–7 and 9); a longer reaction time was needed for 7b
than for 7a and 7c–i. The lower reactivity of 7b is perhaps due
to steric hindrance from the b methyl group. The de-
aromatization reactions of 7e and 7 f were accelerated by
the electron-withdrawing groups (Br or PhCOO, respec-
tively) at the para position, and were completed in shorter
reaction times compared with 7a–d and 7g–i). Products 8a
and 8c–i were sensitive to acid, but were comparatively more
stable than 3 derived from benzylic chlorides. Product 8b with
a quaternary carbon center was very robust, and could be
purified by standard column chromatography on silica gel.
aromatization reaction led us to examine the cinnamyl
chloride 4. We assumed that, if the bis(h3-allyl)palladium
[*] S. Lu, Z. Xu, Prof. Dr. M. Bao
State Key Laboratory of Fine Chemicals
Dalian University of Technology, Dalian 116012 (China)
Fax: (+86)411-8899-3687
E-mail: mingbao@dlut.edu.cn
Prof. Dr. Y. Yamamoto
Department of Chemistry, Graduate School of Science
Tohoku University, Sendai 980-8578 (Japan)
Fax: (+81)22-795-6784
E-mail: yoshi@mail.tains.tohoku.ac.jp
[**] We are grateful to the National Natural Science Foundation of China
(20572010) for financial support. This work was partly supported by
the Program for Changjiang Scholars and Innovative Research
Teams in Universities (IRT0711).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Each of the new products was characterized through NMR[11]
and IR spectroscopy as well as HRMS.
Table 1: Palladium-catalyzed de-aromatization reaction of naphthalene
derivatives 7a–i with allyltributylstannane.[a]
It occurred to us that the two terminal olefinic groups of 8
might undergo a metathesis reaction to construct a new
alicyclic ring. Indeed, when 8b was treated with the ruthe-
nium-carbene catalyst 9,[12] the cyclized product 10 was
isolated in 62% yield [Eq. (3)]. This result further confirmed
[b]
Entry
1
Substrate
t [h]
ProductYield [%]
12
84
82
2
3
24
12
that the configuration of the 1,3-butadiene moiety of 8b was
identical to that presented in Table 1. The de-aromatization
products were very stable under basic conditions, thus
suggesting that 8 f could be hydrolyzed in an NaOH solution
to produce a cyclic ketone derivative without the formation of
any isomerization product. In fact, the desired product 11 was
isolated in 77% yield [Eq. (4)]; it seemed that the function-
alized product 11 might be useful for further manipulation.
82
87
89
4
5
14
2
6
7
6
87
80
A plausible mechanism for the allylative de-aromatization
reaction is shown in Scheme 1. The oxidative addition of 7a to
a Pd0 species would produce the h3-allylpalladium chloride
intermediate 12, which would react with allyltributylstannane
to generate a bis(h3-allyl)palladium intermediate 13 upon
ligand exchange. Isomerization of 13 would occur to give a
bis(h3-allyl)palladium intermediate 13’, which could undergo
14
8
9
18
12
78
74
[a] A solution of naphthalene derivative 7 (0.5 mmol), allyltributylstan-
nane (0.5 mmol), [Pd2(dba)3] (5 mol%), and Ph3P (20 mol%) in
dichloromethane (3 mL) was stirred at room temperature under N2 for
the period indicated. The reaction progress was monitored by TLC.
[b] Yields of isolated product. dba=trans,trans-dibenzylideneacetone.
Scheme 1. Proposed mechanism for the de-aromatization reaction.
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Communications
reductive elimination to form the de-aromatization product
Experimental Section
8a and regenerate the Pd0 catalyst.
General procedure for the allylative de-aromatization reaction:
Allyltributylstannane (165.6 mg, 0.5 mmol) and 7a (101.3 mg,
The successful extension of the allylative de-aromatiza-
tion to the naphthalene derivatives 7a–i encouraged us to
examine the phenanthrene derivatives 7j–l, and the results
are summarized in Table 2. The simple substrate 7j gave the
0.5 mmol) were added to
a solution of [Pd2(dba)3] (22.8 mg,
0.025 mmol) and PPh3 (26.2 mg, 0.1 mmol) in dichloromethane
(3 mL) at room temperature, and the reaction mixture was stirred
for 12h under N 2. After the allyltributylstannane was consumed (as
evident by TLC), the solvent was removed under reduced pressure.
The residue was filtered through a short column of basic alumina to
remove palladium by-products and eluted with pentane to give 8a in
84% yield (87.5 mg) as a colorless liquid.
Table 2: Palladium-catalyzed de-aromatization reaction of phenanthrene
derivatives 7j–l with allyltributylstannane.[a]
Received: February 1, 2008
Published online: April 29, 2008
Keywords: de-aromatization · naphthalenes · palladium ·
.
phenanthrenes · synthetic methods
[b]
Entry
1
Substrate
t [h]
ProductYield [%]
[1] For recent selected references, see: a) F. López Ortiz, M. J.
Iglesias, I. Fernµndez, C. M. Andffljar Sµnchez, G. Ruiz Gómez,
Chem. Rev. 2007, 107, 1580 – 1691; b) J. Gagnepain, F. Castet, S.
Quideau, Angew. Chem. 2007, 119, 1555 – 1557; Angew. Chem.
Int. Ed. 2007, 46, 1533 – 1535; c) E. N. Pitsinos, V. I. Moutsos, O.
Vageli, Tetrahedron Lett. 2007, 48, 1523 – 1526; d) N. Lebrasseur,
J. Gagnepain, A. Ozanne-Beaudenon, J.-M. LØger, S. Quideau, J.
Org. Chem. 2007, 72, 6280 – 6283; e) L. H. Mejorado, T. R. R.
Pettus, J. Am. Chem. Soc. 2006, 128, 15625 – 15631; f) D. Crich, V.
Krishnamurthy, Tetrahedron 2006, 62, 6830 – 6840; g) J. Zhu,
N. P. Grigoriadis, J. P. Lee, J. A. Porco, Jr., J. Am. Chem. Soc.
2005, 127, 9342– 9343.
[2] For the oxidation of phenol and its derivatives, see: a) P. J. Stang,
V. V. Zhdankin, Chem. Rev. 1996, 96, 1123 – 1178; b) N. Leb-
rasseur, G.-J. Fan, M. Oxoby, M. A. Looney, S. Quideau,
Tetrahedron 2005, 61, 1551 – 1562; c) E. N. Pitsinos, A. Cruz,
Org. Lett. 2005, 7, 2245 – 2248; d) S. Quideau, L. PouysØgu, A.
Ozanne, J. Gagnepain, Molecules 2005, 10, 201 – 216; e) L. H.
Mejorado, C. Hoarau, T. R. R. Pettus, Org. Lett. 2004, 6, 1535 –
1538; f) R. W. Van De Water, C. Hoarau, T. R. R. Pettus,
Tetrahedron Lett. 2003, 44, 5109 – 5113; g) S. Mandal, D.
Macikenas, J. D. Protasiewicz, L. M. Sayre, J. Org. Chem. 2000,
65, 4804 – 4809; h) J. S. Swenton, K. Carpenter, Y. Chen, M. L.
Kerns, G. W. Morrow, J. Org. Chem. 1993, 58, 3308 – 3316; also
see Ref. [1g]; for microbial oxidation, see: i) V. Bui, T. V.
Hansen, Y. Stenstrøm, D. W. Ribbons, T. Hudlicky, J. Chem.
Soc. Perkin Trans. 1 2000, 1669 – 1672; j) D. R. Boyd, N. D.
Sharma, N. I. Bowers, J. Duffy, J. S. Harrison, H. Dalton, J.
Chem. Soc. Perkin Trans. 1 2000, 1345 – 1350; k) D. R. Boyd,
N. D. Sharma, S. A. Barr, H. Dalton, J. Chima, G. Whited, R.
Seemayer, J. Am. Chem. Soc. 1994, 116, 1147 – 1148.
[3] For catalytic hydrogenation, see: a) E. Heller, W. Lauten-
schläger, U. Holzgrabe, Tetrahedron Lett. 2005, 46, 1247 – 1249;
b) T. J. Donohoe, R. Garg. C. A. Stevenson, Tetrahedron: Asym-
metry 1996, 7, 317 – 344; for Birch reduction, see: c) A. J. Birch,
Pure Appl. Chem. 1996, 68, 553 – 556.
[4] a) For a review, see: J. Cornelisse, Chem. Rev. 1993, 93, 615 – 669;
b) S. Kohmoto, H. Masu, C. Tatsuno, K. Kishikawa, M.
Yamamoto, K. Yamaguchi, J. Chem. Soc. Perkin Trans. 1 2000,
4464 – 4468, and references therein; c) A. Yokoyama, K.
Mizuno, Org. Lett. 2000, 2, 3457 – 3459, and references therein.
[5] For nitrogen-ylide rearrangement, see: a) N. Shirai, Y. Wata-
nabe, Y. Sato, J. Org. Chem. 1990, 55, 2767 – 2770, and references
therein; for sulfur-ylide rearrangement, see: b) C. C. McComas,
D. L. Van Vranken, Tetrahedron Lett. 2003, 44, 8203 – 8205, and
references therein; c) M. G. Burdon, J. G. Moffatt, J. Am. Chem.
Soc. 1967, 89, 4725 – 4735; d) C. R. Hauser, S. W. Kantor, W. R.
12
87
84
86
2
3
9
21
[a] A solution of phenanthrene derivative 7 (0.5 mmol), allyltributylstan-
nane (0.5 mmol), [Pd2(dba)3] (5 mol%), and Ph3P (20 mol%) in
dichloromethane (3 mL) was stirred at room temperature under N2 for
the period indicated. The reaction progress was monitored by TLC.
[b] Yields of isolated product.
corresponding product 8j in 87% yield (Table 2, entry 1).
Even 7k, with a C(sp3)-H b-hydrogen atom, underwent the
reaction smoothly and afforded 8k as the only product in
84% yield (Table 2, entry 2).[13] The substrate 7l, bearing an
nPr group a to the chlorine atom, also provided the de-
aromatization product 8l in 86% yield, without the formation
of any b-hydride elimination product (Table 2, entry 3). The
products 8j–l are very stable, and each was purified by
standard column chromatography on silica gel. No re-
aromatized compounds were observed.
Even though the de-aromatization of the benzene deriv-
atives 4 bearing allyl chloride was not successful, that of the
naphthalene and phenanthrene derivatives 7 proceeded
readily and efficiently. Perhaps, this difference is due to
lower resonance energies of the aromatic rings of 7 compared
to those of 4.[14] The facile and efficient construction of 8 and
their rather unexpected stability allows the synthesis of
extended fused and functionalized ring systems from naph-
thalenes and phenanthrenes.
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Chemie
Brasen, J. Am. Chem. Soc. 1953, 75, 2660 – 2663; for Still–Wittig
rearrangement, see: e) P. Monje, P. Grana, M. R. Paleo, F. J.
Sardina, Org. Lett. 2006, 8, 951 – 954; f) P. A. Caruana, A. J.
Frontier, Tetrahedron 2004, 60, 10921 – 10926.
de-aromatization reaction involving naphthylborate anions, see:
d) E. Negishi, R. E. Merrill, J. Chem. Soc. Chem. Commun. 1974,
860 – 861.
[9] M. Bao, H. Nakamura, Y. Yamamoto, J. Am. Chem. Soc. 2001,
123, 759 – 760.
[6] For reviews, see: a) J. M. Keane, W. D. Harman, Organometallics
2005, 24, 1786 – 1798; b) W. D. Harman, Coord. Chem. Rev. 2004,
248, 853 – 866; c) A. R. Pape, K. P. Kaliappan, E. P. Kündig,
Chem. Rev. 2000, 100, 2917 – 2940; also see: d) D. A. Delafuente,
W. H. Myers, M. Sabat, W. D. Harman, Organometallics 2005,
24, 1876 – 1885.
[10] H. Nakamura, M. Bao, Y. Yamamoto, Angew. Chem. 2001, 113,
3308 – 3310; Angew. Chem. Int. Ed. 2001, 40, 3208 – 3210.
[11] The structural assignment of product 8 was based on 1D (1H and
13C) and 2D (1H-1H COSY and NOESY) spectrocopic analysis.
For example, the connection and configuration of products 8c
1
and 8h were obtained from H-1H COSY and NOESY spectra.
[7] Arenes were activated by electron-withdrawing groups, see:
a) A. M. Ramallal, I. Fernµndez, F. López Ortiz, J. Gonzµlez,
Chem. Eur. J. 2005, 11, 3022 – 3031, and references therein; b) Z.
Wang, Z. Xi, Synlett 2006, 1275 – 1277; c) J. Clayden, F. E.
Knowles, I. R. Baldwin, J. Am. Chem. Soc. 2005, 127, 2412 –
2413; d) J. Clayden, R. Turnbull, M. Helliwell, I. Pinto, Chem.
Commun. 2004, 2430 – 2431; e) J. Clayden, R. Turnbull, I. Pinto,
Org. Lett. 2004, 6, 609 – 611; f) J. Clayden, M. N. Kenworthy, M.
Helliwell, Org. Lett. 2003, 5, 831 – 834; g) J. Barluenga, S. K.
Nandy, Y. R. S. Laxmi, J. R. Suµrez, I. Merino, J. Flórez, S.
Garcꢀa-Granda, J. Montejo-Bernardo, Chem. Eur. J. 2003, 9,
5725 – 5736; arenes can be activated by complexation to
transition metals, see: h) L. Zhou, L.-Z. Wu, L.-P. Zhang, C.-
H. Tung, Organometallics 2006, 25, 1707 – 1711; i) E. P. Kündig,
A. Bellido, K. P. Kaliappan, A. R. Pape, S. Radix, Org. Biomol.
Chem. 2006, 4, 342– 351; j) F. C. Pigge, J. J. Coniglio, R. Dalvi, J.
Am. Chem. Soc. 2006, 128, 3498 – 3499; k) F. C. Pigge, J. J.
Coniglio, N. P. Rath, Org. Lett. 2003, 5, 2011 – 2014; also see
Ref. [6c].
[12] W. Zhang, C. Bai, X. Lu, R. He, J. Organomet. Chem. 2007, 692,
3563 – 3567.
[13] In the Stille cross-coupling reaction of C(sp3)-X electrophiles,
the b hydride elimination often gave alkenes in preference to
coupling products, see: a) D. J. Cµrdenas, Angew. Chem. 2003,
115, 398 – 401; Angew. Chem. Int. Ed. 2003, 42, 384 – 387; b) T.-Y.
Luh, M.-k. Leung, K.-T. Wong, Chem. Rev. 2000, 100, 3187 –
3204.
[8] For organolanthanide-induced de-aromatization, see: a) R. Liu,
C. Zhang, Z. Zhu, J. Luo, X. Zhou, L. Weng, Chem. Eur. J. 2006,
12, 6940 – 6952; for radical addition, see: b) D. Crich, M.
Sannigrahi, Tetrahedron 2002, 58, 3319 – 3322; c) J. Boivin, M.
Yousfi, S. Z. Zard, Tetrahedron Lett. 1997, 38, 5985 – 5988; for a
[14] DFT computation of intermediates and products are now under
investigation, and a detailed mechanistic discussion will appear
in due course.
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