Rhodium-catalysed cyclisation reaction of allenynes with arylboronic acids

Article abstract of DOI:10.1039/b810665g

Allenynes having malonate-based tethers reacted with arylboronic acids in the presence of a rhodium(I) catalyst to sequentially form three carbon-carbon bonds, and arylated bicyclic skeletons were constructed in a stereoselective manner. The Royal Society of Chemistry.

Full text of DOI:10.1039/b810665g

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Rhodium-catalysed cyclisation reaction of allenynes with
arylboronic acidsw
Tomoya Miura, Keita Ueda, Yusuke Takahashi and Masahiro Murakami*
Received (in Cambridge, UK) 24th June 2008, Accepted 22nd July 2008
First published as an Advance Article on the web 16th September 2008
DOI: 10.1039/b810665g
Allenynes having malonate-based tethers reacted with arylboro-
nic acids in the presence of a rhodium(I) catalyst to sequentially
form three carbon–carbon bonds, and arylated bicyclic skeletons
were constructed in a stereoselective manner.
Recently, the rhodium-catalysed cyclisation reaction with
organoboron reagents has been demonstrated to be a powerful
method for the synthesis of carbocyclic compounds.1 An
organorhodium(I) species, generated through transmetalation
Scheme 1 Reaction of allenyne 1a with phenylboronic acid (2a).
between rhodium(I) and boron, can undergo multiple carbo-
rhodation steps onto acceptor compounds bearing two and
more functional groups to form cyclic skeletons.2 An alkyne
moiety provides an expedient entry point for incorporation of
an organorhodium(I) species in the molecule, which then adds
intramolecularly to another functional group.3 We have pre-
viously described the rhodium-catalysed cyclisation reaction
of 1,6-enynes with arylboronic acids to form arylated bicyclic
compounds with a stereodefined exocyclic double bond.4
Allenyl compounds present a versatile platform for syn-
thetic manipulations due to their unique structure and high
reactivity.5 In pursuit of a new reaction involving multiple
carborhodation steps, we became interested in affecting an
arylative cyclisation reaction using allenynes,6 which have
been employed in other types of cyclisation reactions.7 In this
paper is described a new cyclisation reaction of allenynes with
arylboronic acids.
regioselective 1,2-addition of A across the carbon–carbon
triple bond of 1a occurs to form the alkenylrhodium(I) inter-
mediate B.10 From here, B undergoes intramolecular carbo-
rhodation onto the allene moiety in a 5-exo mode to give
(cyclopentylvinyl)rhodium(I) intermediate C. Finally, intra-
molecular acylation of C with the methoxycarbonyl group
on the tether via addition–elimination affords 3aa regenerating
the catalytically active (methoxo)rhodium(I) species.
The results obtained with various combinations of allenynes
1 and arylboronic acids 2 are summarised in Table 1.z Both
electron-donating and -withdrawing arylboronic acids 2b–2f
were suitably reactive (Entries 1–5). Even sterically hindered
o-tolylboronic acid (2g) participated in the cyclisation reaction
with 1a (Entry 6). The reaction of allenynes 1b–1d having
primary and secondary alkyl groups at the alkyne termini
afforded the corresponding products 3ba–3da in yields ranging
from 61% to 93% (Entries 8–10). Allenynes 1e and 1f having a
di-substituted allene terminus were also converted to the
corresponding products 3ea and 3fa, albeit in lower yields
than that of 1a (Entries 11 and 12). On the other hand, the
When allenyne (1a, 1.0 equiv.) was treated with phenyl-
boronic acid (2a, 1.5 equiv.) in the presence of [RhCl(cod)]2
(5 mol% Rh, cod = cycloocta-1,5-diene) and KOH (0.5 equiv.)
in THF at 50 1C for 12 h, bicyclo[2.2.1]heptan-2-one 3aa was
obtained in 24% yield together with the starting material 1a
(28%) and the cycloisomerisation product 4 (10%)8 (Scheme 1).
The (Z)-configuration of the exocyclic double bond of 3aa was
determined by an NOE study. Remarkably, the use of
[RhCl(nbd)]2 (5 mol% Rh, nbd = norborna-2,5-diene) as
the catalyst suppressed the formation of 4 and the yield of
3aa increased to 76%.
We speculate the possible reaction pathway as depicted in
Scheme 2 for the production of 3aa starting from 1a and 2a,
although we have no experimental evidence for the intermedi-
ate species. Initially, phenylrhodium(I) species A is generated
by the transmetalation between rhodium(I) and 2a.9 Then,
Department of Synthetic Chemistry and Biological Chemistry, Kyoto
University, Katsura, Kyoto, 615-8510, Japan.
E-mail: murakami@sbchem.kyoto-u.ac; Fax: +81 75 383 2748;
Tel: +81 75 383 2747
w Electronic supplementary information (ESI) available: General ex-
perimental information and spectral data. See DOI: 10.1039/b810665g
Scheme 2 A plausible mechanism for the catalysed cyclisation
reaction.
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Table 1 Rh(I)-catalysed cyclisation reaction of 1 with 2a
Entry Substrate
ArB(OH)2
Product Yield (%)b
1
2
3
4
5
6
7
8
9
10
1a R = Me
1a R = Me
1a R = Me
1a R = Me
1a R = Me
1a R = Me
1a R = Me
1b R = Et
2b 4-Br-C6H4
2c 3-Br-C6H4
2d 3-Cl-C6H4
2e 3-MeO-C6H4
3ab
3ac
3ad
3ae
70
62
65
73
61
61
46
87
61
93c
2f 3-MeO2C-C6H4 3af
2g 2-Me-C6H4
2h 3-Thienyl
2a Ph
2a Ph
2a Ph
3ag
3ah
3ba
3ca
3da
1c R = CH2OMe
1d R = i-Pr
Scheme 3 Reaction of substrates having a four-carbon tether with 2a.
11
12
13
a
1e R,R0 = -(CH2)5- 2a Ph
1f R,R0 = Me, Ph 2a Ph
1g R,R0 = Me, H 2a Ph
3ea
3fa
3ga
71
36
—
be considerably less reactive than 1a. When 5a and 5b were
treated with 2a (5.0 equiv.) in the presence of [Rh(OH)(cod)]2
(5 mol% Rh) under more forcing conditions, intramolecular
carborhodation onto the allene moiety occurred in a 6-exo
mode, and bicyclo[2.2.2]octan-2-ones 6a and 6b were obtained
in 60% and 58% yields, respectively. In contrast, 1,7-enyne 7
failed to cyclise in a 6-exo mode, instead afforded the 1,2-adduct
8 by protonolysis as the major product (72%). Thus, the allenyl
groups of 5a and 5b were more reactive than the isopropenyl
group of 7. In the reaction of allenyne 9 having a four-carbon
tether, bicyclo[3.2.1]octan-6-one 10 was produced in 45% yield.
In summary, we have developed a new rhodium-catalysed
cyclisation reaction of allenynes with arylboronic acids, which
provides a unique access to bicyclic compounds that were
otherwise difficult to form. The reaction also demonstrates
that the allene moiety serves as the acceptor of the in situ
generated organorhodium(I) species in a cascade reaction.11
We thank Mr H. Fujita (Kyoto University) for his assis-
tance in the structural determination by NMR. This work was
supported in part by Grant-in-Aids for Young Scientists (B)
18750084 and Scientific Research on Priority Areas 18032040
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Conditions: 1 (0.1 mmol), 2 (0.15 mmol), [RhCl(nbd)]2 (2.5 mmol,
5 mol%), KOH (50 mmol) in THF (1.5 mL) at 50 1C for 12 h under
Ar. Isolated yield unless otherwise noted. c 1H NMR yield using
CHBr2CHBr2 as an internal standard.
b
allenyne 1g with a mono-substituted allene terminus gave a
complex mixture, and none of the desired product 3ga was
obtained (Entry 13).
Interestingly, allenynes 1h and 1i possessing malononitrile
and acetylacetone tethers underwent an analogous cyclisation
reaction to afford the bicyclic products 3ha and 3ia through
intramolecular addition onto the cyano and ketocarbonyl
groups [eqn (1)].
Notes and references
z General procedure: To an oven-dried flask was added [RhCl(nbd)]2
(1.3 mg, 2.7 mmol, 5 mol% Rh), KOH (3.0 mg, 53 mmol), organo-
boronic acid 2 (0.15 mmol, 1.5 equiv.) and a solution of allenyne 1
(0.10 mmol, 1.0 equiv.) in dry THF (1.5 mL). The reaction mixture was
stirred at 50 1C for 12 h under an argon atmosphere, and then
quenched with addition of water (2.0 mL). The resulting aqueous
solution was extracted with ethyl acetate (4 ꢁ 10 mL). The combined
extracts were washed with brine and dried over MgSO4. The solvent
was removed under reduced pressure and the residue was purified by
ð1Þ
Next, we examined the possibility of a cyclisation reaction in
a 6-exo mode using allenynes equipped with a tether longer by
one carbon (Scheme 3). The allenynes 5a and 5b were found to
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preparative thin-layer chromatography (hexane–ethyl acetate = 10 : 1
or 5 : 1) to give the corresponding bicyclic compounds 3.
5 Modern Allene Chemistry, ed. N. Krause and A. S. K. Hashmi,
Wiley-VCH, Weinheim, 2004.
6 For the palladium-catalysed reaction, see: A. K. Gupta, C. Y.
Rhim and C. H. Oh, Tetrahedron Lett., 2005, 46, 2247.
7 For recent examples, see: (a) C. V. Bray, S. Derien, P. H. Dixneuf
´
1 For a review, T. Miura and M. Murakami, Chem. Commun., 2007,
217.
2 For representative examples, see: (a) M. Lautens and J. Mancuso, Org.
Lett., 2002, 4, 2105; (b) D. F. Cauble, J. D. Gipson and M. J. Krische,
J. Am. Chem. Soc., 2003, 125, 1110; (c) M. Lautens and J. Mancuso,
J. Org. Chem., 2004, 69, 3478; (d) N.-W. Tseng, J. Mancuso and M.
Lautens, J. Am. Chem. Soc., 2006, 128, 5338; (e) T. Miura, T.
Harumashi and M. Murakami, Org. Lett., 2007, 9, 741.
3 For representative examples, see: [aldehyde] (a) R. Shintani, K.
Okamoto, Y. Otomaru, K. Ueyama and T. Hayashi, J. Am. Chem.
Soc., 2005, 127, 54; [ketone] (b) T. Miura, M. Shimada and M.
Murakami, Tetrahedron, 2007, 63, 6131; [nitrile] (c) T. Miura, H.
Nakazawa and M. Murakami, Chem. Commun., 2005, 2855;
[isocyanate] (d) T. Miura, Y. Takahashi and M. Murakami, Org.
Lett., 2007, 9, 5075; [electron-deficient alkene] (e) M. Lautens and
T. Marquardt, J. Org. Chem., 2004, 69, 4607; (f) Y. Chen and C.
Lee, J. Am. Chem. Soc., 2006, 128, 15598; [alkene] (g) M. Shimada,
T. Harumashi, T. Miura and M. Murakami, Chem.–Asian J., 2008,
3, 1035; [alkyne] (h) T. Miura, M. Yamauchi and M. Murakami,
Synlett, 2007, 2029; [halide] (i) Y. Harada, J. Nakanishi, H.
Fujihara, M. Tobisu, Y. Fukumoto and N. Chatani, J. Am. Chem.
Soc., 2007, 129, 5766.
and M. Murakami, Synlett, 2008, 193; (b) O. Buisine, V. Gandon,
L. Fensterbank, C. Aubert and M. Malacria, Synlett, 2008, 751; (c)
K. M. Brummond, D. Chen, T. O. Painter, S. Mao and D. D.
Seifried, Synlett, 2008, 759; (d) C. H. Oh and A. Kim, Synlett,
2008, 777; (e) T. Hirose, N. Miyakoshi and C. Mukai, J. Org.
Chem., 2008, 73, 1061; (f) P. H. Cheong, P. Morganelli, M. R.
Luzung, K. N. Houk and F. D. Toste, J. Am. Chem. Soc., 2008,
130, 4517. See references therein for other examples.
8 For previous reports on cycloisomerisation forming 4, see: (a) K.
M. Brummond, H. Chen, P. Sill and L. You, J. Am. Chem. Soc.,
2002, 124, 15186; (b) T. Shibata, Y. Takesue, S. Kadowaki and K.
Takagi, Synlett, 2003, 268.
9 P. Zhao, C. D. Incarvito and J. F. Hartwig, J. Am. Chem. Soc.,
2007, 129, 1876.
10 (a) T. Hayashi, K. Inoue, N. Taniguchi and M. Ogasawara, J. Am.
Chem. Soc., 2001, 123, 9918; (b) M. Lautens and M. Yoshida, Org.
Lett., 2002, 4, 123; (c) M. Murakami and H. Igawa, Helv. Chim.
Acta, 2002, 85, 4182; (d) E. Genin, V. Michelet and J.-P. Genet,
J. Organomet. Chem., 2004, 689, 3820.
11 For intermolecular addition of organorhodium(I) species to
allenes, see: T. Nishimura, S. Hirabayashi, Y. Yasuhara and
T. Hayashi, J. Am. Chem. Soc., 2006, 128, 2556.
4 T. Miura, T. Sasaki, H. Nakazawa and M. Murakami, J. Am.
Chem. Soc., 2005, 127, 1390.
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5368 | Chem. Commun., 2008, 5366–5368