Rhodium-catalyzed olefin isomerization/allyl claisen rearrangement/ intramolecular hydroacylation cascade

Article abstract of DOI:10.1021/ol400574s

It has been established that a cationic Rh(I)/dppf complex catalyzes the olefin isomerization/allyl Claisen rearrangement/intramolecular hydroacylation cascade of di(allyl) ethers to produce substituted cyclopentanones in good yields under mild conditions.

Full text of DOI:10.1021/ol400574s

ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Rhodium-Catalyzed Olefin Isomerization/
Allyl Claisen Rearrangement/
Intramolecular Hydroacylation Cascade
Ryuichi Okamoto† and Ken Tanaka*,‡
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of
Agriculture and Technology, Koganei, Tokyo 184-8588, Japan, and JST, ACT-C,
4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan
tanaka-k@cc.tuat.ac.jp
Received March 2, 2013
ABSTRACT
It has been established that a cationic Rh(I)/dppf complex catalyzes the olefin isomerization/allyl Claisen rearrangement/intramolecular
hydroacylation cascade of di(allyl) ethers to produce substituted cyclopentanones in good yields under mild conditions.
The transition-metal-catalyzed intramolecular hydro-
acylation of 4-alkenals is a useful method for the synthesis
of substituted cyclopentanones.1À4 However, the synthesis of
Scheme 1
substituted 4-alkenals is sometimes troublesome. Further-
more, theyare unstable under air and gradually oxidized to
† Tokyo University of Agriculture and Technology.
‡ JST, ACT-C.
(1) For a review, see: Willis, M. C. Chem. Rev. 2010, 110, 725.
(2) For pioneering work, see: Sakai, K.; Ide, J.; Nakamura, N.
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(3) For examples, see: (a) Hoffman, T. J.; Carreira, E. M. Angew.
Chem., Int. Ed. 2011, 50, 10670. (b) Vautravers, N. R.; Regent, D. D.;
Breit, B. Chem. Commun. 2011, 47, 6635. (c) Hyatt, I. F. D.; Anderson,
H. K.; Morehead, A. T., Jr.; Sargent, A. L. Organometallics 2008, 27,
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(e) Kundu, K.; McCullagh, J. V.; Morehead, A. T., Jr. J. Am. Chem. Soc.
2005, 127, 16042. (f) Morgan, J. P.; Kundu, K.; Doyle, M. P. Chem.
Commun. 2005, 3307. (g) Tanaka, M.; Sakai, K.; Suemune, H. Cur. Org.
Chem. 2003, 7, 353. (h) Tanaka, M.; Imai, M.; Fujio, M.; Sakamoto, E.;
Takahashi, M.; Eto-Kato, Y.; Wu, X.-M.; Funakoshi, K.; Sakai, K.;
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C. G. J. Organomet. Chem. 1985, 285, 321. (q) Sakai, K.; Ishiguro, Y.;
Funakoshi, K.; Ueno, K.; Suemune, H. Tetrahedron Lett. 1984, 961. (r)
James, B. R.; Young, C. G. J. Chem. Soc., Chem. Commun. 1983, 1215.
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190. (t) Lochow, C. F.; Miller, R. G. J. Am. Chem. Soc. 1976, 98, 1281.
the corresponding carboxylic acids. Therefore, the use
of readily prepared and stable 4-alkenal equivalents is
(4) For selected recent examples of the Rh(I)-catalyzed alkene hydro-
acylation, see: (a) von Delius, M.; Le, C. M.; Dong, V. M. J. Am. Chem.
Soc. 2012, 134, 15022. (b) Chaplin, A. B.; Hooper, J. F.; Weller, A. S.;
Willis, M. C. J. Am. Chem. Soc. 2012, 134, 4885. (c) Shibata, Y.; Tanaka,
K. J. Am. Chem. Soc. 2009, 131, 12552. (d)Coulter, M. M.; Dornan, P. K.;
Dong, V. M. J. Am. Chem. Soc. 2009, 131, 6932. (e) Moxham, G. L.;
Randell-Sly, H. E.; Brayshaw, S. K.; Woodward, R. L.; Weller, A. S.;
Willis, M. C. Angew. Chem., Int. Ed. 2006, 45, 7618 and references therein.
r
10.1021/ol400574s
XXXX American Chemical Society

highly desired. In 1995, Eilbracht and co-workers reported
the transition-metal-catalyzed olefin isomerization/allyl
Claisen rearrangement/intramolecular hydroacylation cas-
cade of di(allyl) ether A to produce substituted cyclopenta-
none D by using a neutral Rh(I)/dppe or Ru(II)/PPh3
complex (Scheme 1).5a In this cascade reaction, the metal-
catalyzed chemoselective olefin isomerization of the mono-
substituted alkene moiety of A proceeds to give alkenyl
ether B. Subsequent thermal allyl Claisen rearrangement
affords 4-alkenal C. Metal-catalyzed intramolecular hydro-
acylation of C affords cyclopentanone D. However, harsh
reaction conditions (140À220 °C under CO atmosphere)
were required and the yields of D were not satisfactory.
On the other hand, our research group reported the
cationic Rh(I)/bisphosphine complex-catalyzed olefin iso-
merization/propargyl Claisen rearrangement/carbonyl mi-
gration cascade of allyl propargyl ethers possessing the 1,
1-disubstituted alkene moiety at 80 °C.6 In this cascade
reaction, the olefin isomerization of the 1,1-disubstituted
alkene moiety proceeds smoothly. Thus, we designed the
following Rh(I)-catalyzed cascade reaction using di(allyl)
ether 1 possessing the 1,1- and 1,2-disubstituted alkene
moieties (Scheme 2). If the cationic Rh(I)/bisphosphine
complex catalyzes the chemoselective isomerization of the
1,1-disubstituted alkene moiety of 1, the corresponding
alkenyl ether 2 would be generated.7 The subsequent
thermal allyl Claisen rearrangement of 2, which would be
accelerated by the Lewis acidic cationic Rh(I) complex,
would proceed at a lower temperature to afford 4-alkenal 3.8
The Rh(I)-catalyzed intramolecular hydroacylation of 3
would afford cyclopentanone 4. Herein, we disclose our
successoftheabove-mentioned cascadereactionby usinga
cationic Rh(I)/dppf catalyst under mild conditions.
Scheme 2
Table 1. Optimization of Reaction Conditionsa
We first investigated the reaction of di(allyl) ether 1a in
the presence of a cationic Rh(I)/dppe complex (10 mol %)
at 80 °C (Table 1, entry 1). Pleasingly, the desired cyclo-
pentanone 4a was obtained in moderate yield, while
3-alkenal 5a was generated as a byproduct. Screening of
bisphosphine ligands (entries 1À5) revealed that the use of
(5) (a) Eilbracht, P.; Gersmeir, A.; Lennartz, D.; Huber, T. Synthesis
1995, 330. For examples of the transition-metal-catalyzed allyl Claisen
rearrangement/intramolecular hydroacylation cascade, see: (b) Sattelkau,
T.; Eilbracht, P. Tetrahedron Lett. 1998, 39, 1905. (c) Dygutsch, D. P.;
Eilbracht, P. Tetrahedron 1996, 52, 5461.
a [Rh(cod)2]BF4 (0.010 mmol), ligand (0.010 mmol), 1a (0.10 mmol),
and (CH2Cl)2 (1.5 mL) were used. b Isolated yield. c [Rh(nbd)2]BF4 was
used. d NMR yield. e [Rh(cod)2]BF4 (0.015 mmol), ligand (0.015 mmol),
1a (0.30 mmol), and (CH2Cl)2 (1.5 mL) were used.
(6) Tanaka, K.; Okazaki, E.; Shibata, Y. J. Am. Chem. Soc. 2009,
131, 10822.
(7) For a recent review of the transition-metal-catalyzed olefin iso-
merization, see: Tanaka, K. In Comprehensive Organometallic Chemis-
try III; Crabtree, R. H., Mingos, D. M. P., Ojima, I., Eds.; Elsevier: Oxford,
2007; Vol. 10, p 71.
dppf afforded 4a in the highest yield without the formation
of 5a (entry 5). At rt, the chemoselective isomerization of
the 1,1-disubstituted alkene moiety of 1a proceeded to give
the corresponding alkenyl ether 2a without forming dienes E
and F, while 4-alkenal 3a was generated in low yield and
cyclopentanone 4a was not generated at all (entry 6). Finally,
the catalyst loading could be reduced to 5 mol % without
erosion of the product yield and ee value (entry 7).
With the optimized reaction conditions in hand, the
scope of this cascade reaction was examined (Table 2).9
With respect to substituents at the 1,2-disubstituted alkene
moiety (R1), di(allyl) ethers 1aÀh possessing electronically
(8) For recent examples of the sequential olefin isomerization/allyl
Claisen rearrangement of di(allyl) ethers, see: (a) McLaughlin, M. G.;
Cook, M. J. J. Org. Chem. 2012, 77, 2058. (b) Geherty, M. E.; Dura,
R. D.; Nelson, S. G. J. Am. Chem. Soc. 2010, 132, 11875. (c) Kerrigan,
N. J.; Bungard, C. J.; Nelson, S. G. Tetrahedron 2008, 64, 6863. (d)
Wang, K.; Bungard, C. J.; Nelson, S. G. Org. Lett. 2007, 9, 2325. (e)
Stevens, B. D.; Bungard, C. J.; Nelson, S. G. J. Org. Chem. 2006, 71,
6397. (f) Trost, B. M.; Zhang, T. Org. Lett. 2006, 8, 6007. (g) Nelson,
S. G.; Wang, K. J. Am. Chem. Soc. 2006, 128, 4232. (h) Nevado, C.;
Echavarren, A. M. Tetrahedron 2004, 60, 9735. (i) Schmidt, B. Synlett
2004, 1541. (j) Nelson, S. G.; Bungard, C. J.; Wang, K. J. Am. Chem. Soc.
2003, 125, 13000. (k) Le Notre, J.; Brissieux, L.; Semeril, D.; Bruneau,
C.; Dixneuf, P. H. Chem. Commun. 2002, 1772. (l) Ben Ammar, H.; Le
Notre, J.; Salem, M.; Kaddachi, M. T.; Dixneuf, P. H. J. Organomet.
Chem. 2002, 662, 63 and references therein.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 2. Scope of 1,6-Dienesa
Scheme 4
Scheme 5
a Reactions were conducted using [Rh(cod)2]BF4 (0.015 mmol), dppf
(0.015 mmol), 1aÀl (0.30 mmol), and (CH2Cl)2 (1.5 mL) at 80 °C for
16 h. b Isolated yield. c MS4A (100 wt % of 1l) was used.
Scheme 3
diastereoselectivities of 4j and 4k were low (entries
11 and 10). The reaction of monosubstituted 1,6-diene 1l was
examined, but a partial hydrolysis of the allyl ether moiety
was observed. The addition of MS4A suppressed the un-
desired hydrolysis to give the corresponding cyclopentanone
4l in 37% yield with high diastereoselectivity (entry 12).
In general, rhodium-catalyzed hydroacylation reactions
require high catalyst loadings due to the formation of
catalytically inactive rhodium carbonyl complexes3o and
the presence of small amounts of carboxylic acid impu-
rities. Especially, sterically demanding R,R-disubstituted
4-alkenals require a higher catalyst loading. Pleasingly, the
large-scale reaction of 1a proceeded in the presence of 1
mol % of the cationic Rh(I)/dppf complex to give 4a in
high yield, presumably as a result of the gradual in situ
formation of 4-alkenal 3a from 1a under an inert atmo-
sphere (Scheme 3).
and sterically diverse aryl groups could be employed for
this process (entries 1À8). Heteroaryl-substituted di(allyl)
ether 1i could also be employed (entry 9). Unfortunately,
the reaction of alkyl-substituted di(allyl) ether 1j afforded
the corresponding cyclopentanone 4j in low yield due
to the formation of a mixture of undesired olefin isomer-
ization products (entry 10). With respect to substituents at
the 1,1-disubstituted alkene moiety (R2), phenyl-substituted
di(allyl) ether 1k afforded the corresponding cyclopenta-
none 4k in good yield (entry 11). Unfortunately, the
Importantly, the present cascade process can also em-
ploy di(allyl) ethers possessing the trisubstituted alkene
moiety. The reaction of 3-(p-tolyl)but-2-en-1-ol derivative
1m, which was prepared from 1-(p-tolyl)ethanone (6) and
ethyl 2-(diethoxyphosphoryl)acetate (7) via ester 8, also
proceeded to give cyclopentanone 4m [(()-R-cuparenone10]
in good yield (Scheme 4).
(9) The reaction of di(allyl) ether 1p possessing two 1,2-disubstituted
alkene moieties afforded 4-alkenal 10 presumably through the chemo-
selective isomerization of the methyl-substituted alkene moiety to form
alkenyl ether H followed by a 1,3-allylic rearrangement. The reaction of
di(allyl) ether 1q possessing two 1,1-disubstituted alkene moieties
afforded di(alkenyl) ether 11.
The reaction of cyclopentadiene derivative 1n
proceeded to give spirocyclic cyclopentanone 4n in
(10) For examples of the synthesis of R-cuparenone, see: (a) Nishii,
T.; Miyamae, F.; Yoshizuka, M.; Kaku, H.; Horikawa, M.; Inai, M.;
Tsunoda, T. Tetrahedron: Asymmetry 2012, 23, 739. (b) Gottumukkala,
A. L.; Matcha, K.; Lutz, M.; de Vries, J. G.; Minnaard, A. J. Chem.;
Eur. J. 2012, 18, 6907. (c) Zhang, P.; Le, H.; Kyne, R. E.; Morken, J. P.
J. Am. Chem. Soc. 2011, 133, 9716. (d) Shivakumar, I.; Salunke, G. B.;
Kumar, S. Synth. Commun. 2011, 41, 1952 and references therein.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 6
Scheme 8
Scheme 7
Furthermore, we have established that the present cas-
cade reaction is an intramolecular process. Treatment of a
1:1 mixture of deuterated di(allyl) ether 1a-d2 and non-
deuterated di(allyl) ether 1c with the cationic Rh(I)/dppf
complex furnished deuterated 4a-d2 and nondeuterated 4c,
and thus no deuterium crossover was observed (Scheme 7).
Scheme 8 depicts a plausible mechanism for the present
cascade reaction. The rhodium-catalyzed chemoselective
isomerization of the 1,1-disubstituted alkene moiety of
di(allyl) ether 1 proceeds to afford alkenyl ether 2 through
the intramolecular hydrogen migration.13 The thermal
allyl Claisen rearrangement of 2 affords 4-alkenal 3.14,15
An oxidative addition of the aldehyde CÀH bond of 3 to
rhodium affords rhodium acyl hydride G. Endo addition
of the rhodium hydride to the alkene followed by reductive
elimination furnishes cyclopentanone 4 and regenerates
the Rh(I) catalyst. On the other hand, in the reaction of 1o,
exo addition followed by reductive elimination also pro-
ceeds to give cyclobutanone 9o. Deuterium scrambling at
the R- and β-positions of cyclopentanone4a-d2 was already
explained by a reversible rhodium hydride addition/
β-hydride elimination sequence.3n
moderate yield (Scheme 5).11 Interestingly, that of
cyclohexadiene derivative 1o afforded spirocyclic
cyclobutanone 9o with perfect diastereoselectivity along
with spirocyclic cyclopentanone 4o, although the prod-
uct yields were low (Scheme 5). It is worthy of note that
this is the first example of the cyclobutanone synthesis via
the metal-catalyzed intramolecular hydroacylation of the
4-alkenal.12
In order to gain mechanistic insight into this reaction,
the reaction of a deuterated 1,6-diene in the presence of the
cationic Rh(I)/dppf complex was investigated. Deuterium
from di(allyl) ether 1a-d2 was incorporated into three
different positions of cyclopentanone 4a-d2 as shown in
Scheme 6.
In conclusion, it has been established that a cationic
Rh(I)/dppf complex catalyzes the olefin isomerization/
allyl Claisen rearrangement/intramolecular hydroacyla-
tion cascade of di(allyl) ethers to produce substituted cyclo-
pentanones in good yields under mild conditions. Future
work will focus on further utilization of the cationic Rh(I)
catalysts for the development of novel cascade reactions.
(11) For examples of the spirocyclic cyclopentanone synthesis via the
transition-metal-catalyzed intramolecular hydroacylation of 4-alkenals,
see: (a) Bjoernstad, V.; Undheim, K. Synthesis 2008, 962. (b) Tanaka,
M.; Takahashi, M.; Sakamoto, E.; Imai, M.; Matsui, A.; Fujio, M.;
Funakoshi, K.; Sakai, K.; Suemune, H. Tetrahedron 2001, 57, 1197. (c)
See also refs 3s, 5a, and 5b.
(12) The cyclobutanone synthesis via the transition-metal-catalyzed
intramolecular hydroacylation of 4-alkynals was reported. See: Tanaka,
K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 8078.
(13) A mechanism via π-allyl intermediates has been proposed for the
cationic Rh(I)/bisphosphine complex-catalyzed isomerization of allyl
Acknowledgment. This work was supported partly by
Grants-in-Aid for Scientific Research (Nos. 20675002 and
23105512) from MEXT and ACT-C from JST (Japan). We
are grateful to Umicore for the generous support in
supplying rhodium complexes.
ꢀ
ethers. See: (a) Fatig, T.; Soulie, J.; Lallemand, J.-Y.; Mercier, F.;
Mathey, F. Tetrahedron 2000, 56, 101. (b) Hiroya, K.; Kurihara, Y.;
Ogasawara, K. Angew. Chem., Int. Ed. Engl. 1995, 34, 2287.
(14) For reviews, see: (a) Castro, A. M. M. Chem. Rev. 2004, 104,
2939. (b) Ziegler, F. E. Chem. Rev. 1988, 88, 1423.
(15) The reaction of 1a in the presence of a cationic Rh(I)/(R)-BINAP
complex (10 mol %) at rt afforded 3a with 14% ee. This result suggests
that the cationic Rh(I) complex might partly contribute to the allyl
Claisen rearrangement step.
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.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX