Rh(I)-catalyzed cyclization of 1-arylprop-2-yn-1-ol derivatives utilizing rhodium 1,4-migration

Article abstract of DOI:10.1021/ja042581o

A highly useful method for the construction of cyclopentanone derivatives fused with aromatic ring based on hydrorhodation-1,4-rhodium migration sequence is achieved. Treatment of 1-aryl-prop-2-yn-1-ols, which are easily accessible via an addition of acetylides to the corresponding aryl aldehydes, with a catalytic amount of [Rh(cod)₂]₂(BF₄) and P(p-tolyl)₃ in the presence of a base gives cyclopentanone derivatives in moderate to good yield. Copyright

Full text of DOI:10.1021/ja042581o

Published on Web 02/16/2005
Rh(I)-Catalyzed Cyclization of 1-Arylprop-2-yn-1-ol Derivatives Utilizing
Rhodium 1,4-Migration
Hokuto Yamabe, Akio Mizuno, Hiroyuki Kusama, and Nobuharu Iwasawa*
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
Received December 10, 2004; E-mail: niwasawa@chem.titech.ac.jp
Construction of a cyclopentanone ring onto aromatic compounds
is highly useful, as these bicyclic compounds have abundant use
as synthetic intermediates.1-4 The most direct method for this
transformation is the intramolecular Friedel-Crafts acylation of
3-arylpropanoic acid derivatives;2 however, this method usually
Table 1. Reaction of Propargyl Alcohol 1aa
necessitates the use of strong acids such as AlCl3, CF3SO3H, and
so forth, and is not easy to be applied for the heteroaromatic
compounds. For example, pyridine derivatives are well-known to
be resistant to standard Friedel-Crafts acylation conditions, and
other heteroaromatics such as furan, thiophene, pyrrole, and indole
derivatives have not been employed extensively compared with
benzene derivatives.5 Thus, it is desirable to develop a concise
method for the formation of a cyclopentanone ring onto aromatic
systems, which is applicable to various heteroaromatic compounds.
To carry out this process under mild conditions in a catalytic
manner, we have designed the following reaction based on
transition-metal-catalyzed intramolecular C-H bond activation
(Scheme 1). Treatment of propargyl alcohols 1, easily accessible
via an addition of acetylides to the corresponding aryl aldehydes,
with a certain transition-metal complex in the presence of a base
would give alkoxo complexes A, which would give alkynyl ketones
B and hydride complex (M-H) via â-hydride elimination. Suc-
cessive hydrometalation6 of the alkynyl ketones would give
alkenylmetallic species C. Then, 1,4-metal migration would occur
through the C-H insertion of the alkenylmetallic species to the
ortho-position of the aryl group to give arylmetallic intermediates
D.7 Conjugate addition of the intermediates D would give enolates
E,8 which undergo proton exchange with the alcoholic substrate 1
to regenerate the alkoxo complex A.
entry
PR3
base (equiv)
temp (
°
C)
solvent
time
yield (%)
1
2
3
4
5
6
7
PPh3
BuLi (0.1)
TMP (1.0)
TMP (1.0)
TMP (1.0)
rt
rt
toluene 14 d
toluene 7 d
toluene 17 h
toluene 14 h
toluene 3 h
36
40
36
N. R.
80
PPh3
PPh3
PCy3
90
90
90
67
67
P(p-toyl)3 TMP (1.0)
P(p-toyl)3 TMP (1.0)
P(p-toyl)3 TMP (0.1)
THF
THF
4 h
17 h
86
64
a TMP ) 2,2,6-tetramethylpiperidine; rt ) room temperature.
the reaction conditions, we examined the effect of the base and the
phosphine, and the results are summarized in Table 1. Not only a
strong base such as BuLi but also a weak base such as 2,2,6,6-
tetramethylpiperidine (TMP) is employable in this reaction (entry
2). Higher temperature accelerated the reaction considerably (entry
3). As for the effect of the phosphine and the solvent, P(p-tolyl)3
in either toluene or THF was found to be the most effective to
give the cyclized product 2a in 80 and 86% yield, respectively
(entries 5 and 6), while alkyl phosphine did not promote the reaction
at all (entry 4). Use of a catalytic amount of TMP retarded the
reaction (entry 7).
The reactions of several substrates 1b to 1k were examined under
the optimized conditions (Table 2). Not only electron-donating
(entries 1 and 4) but also electron-withdrawing substituents (entry
2) on the phenyl ring were tolerated for this cyclization to give the
corresponding indanone derivatives in good yield. The phenyl
substituent on alkyne was also employable to give the cyclized
product in moderate yield (entry 3). In the case of the reaction using
naphthalene derivative 1f, cyclopenta[b]naphthalene derivative 2f
was obtained as a major product, which is not easily available by
the standard Friedel-Crafts reaction (entry 5). It is noteworthy that
3-pyridyl derivative 1g also gave the cyclized product in 51% yield,
which cannot be obtained by intramolecular Friedel-Crafts acy-
lation due to the inherent basicity of the substrate (entry 6).
Furthermore, substrates possessing a five-membered heteroaromatic
ring can also be employed; reaction of 2-pyrrolyl-, 2-thienyl-,
3-thienyl-, and 1-(3-furyl)-prop-2-yn-1-ol derivatives all gave the
corresponding cyclopentanones in moderate to good yield (entries
7-10).10
On the basis of these considerations, we examined the reaction
of propargyl alcohol 1a with several transition-metal complexes in
the presence of a base. Late transition metals such as Ru(II), Pt-
(II), and Ir(I)-phosphine complexes did not show the activity for
this transformation.9 Gratifyingly, treatment of 1a with 10 mol %
of [Rh(cod)2](BF4) and 40 mol % of PPh3 in the presence of 10
mol % of BuLi as a base at room temperature gave the desired
indanone derivative 2a in 36% yield (Table 1, entry 1). To optimize
Scheme 1
To elucidate the mechanism of this reaction, we next carried
out a deuterium-labeling study. The reaction of deuterium-labeled
1a-d (>98% d incorporated in the propargyl position) revealed that
the deuterium at this position was exclusively transferred to the
â-position of the carbonyl group (Scheme 2). Additionally, when
the substrate possessing deuterium at the ortho- and para-positions
of the phenyl ring (1a-d3) was employed, deuterium was incor-
porated in the position R to the carbonyl.11 Furthermore, when a
9
3248
J. AM. CHEM. SOC. 2005, 127, 3248-3249
10.1021/ja042581o CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Catalytic Cyclization of Aryl- or
Scheme 3
Heteroaryl-prop-2-yn-1-olsa
1,4-rhodium migration sequence. This method allows a very easy
preparation of various types of cyclopentanone derivatives fused
with aromatic ring from the corresponding aryl and heteroaromatic
aldehydes.
Acknowledgment. This research was partly supported by the
Novartis Science Foundation and a Grant-in-Aid for Scientific
Research from Ministry of Education, Culture, Sports, Science and
Technology of Japan. H.Y. was granted a Research Fellowship of
the Japan Society for the Promotion of Science for Young Scientists.
Supporting Information Available: Preparative methods and
spectral and analytical data of compounds 1-4 (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
References
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a Conditions: 10 mol % [Rh(cod)2](BF4), 40 mol % P(p-tolyl)3, 100 mol
% TMP, toluene, 90 °C. b Reaction in THF at 67 °C. c Reaction in toluene
at 100 °C. d 20 mol % of [Rh(cod)2](BF4) and 80 mol % of P(p-tolyl)3
were used.
(5) For examples of Friedel-Crafts-type acylation onto heteroaromatic
compounds, see: Komoto, I.; Matsuo, J.; Kobayashi, S. Top. Catal. 2002,
19, 43 and references therein.
Scheme 2
(6) For examples of hydrorhodation, see: (a) Sato, S.; Matsuda, I.; Shibata,
M. J. Organomet. Chem. 1989, 377, 347. (b) Sato, S.; Matsuda, I.; Izumi,
Y. J. Organomet. Chem. 1989, 359, 255. (c) Sato, S.; Matsuda, I.; Izumi,
Y. J. Organomet. Chem. 1988, 344, 71.
(7) For a review of 1,4-Pd migration, see: (a) Dyker, G. In Transition Metals
for Organic Synthesis; Beller, M., Bolm, C., Eds.; Wiley: Weinheim,
Germany, 1998; p 241. For recent examples of synthetic use of 1,4-Pd
migrations, see: (b) Campo, M. A.; Larock, R. C. J. Am. Chem. Soc.
2002, 124, 14326. (c) Campo, M. A.; Huang, Q.; Yao, T.; Tian, Q.; Larock,
R. C. J. Am. Chem. Soc. 2003, 125, 11506. (d) Huang, Q.; Campo, M.
A.; Yao, T.; Tian, Q.; Larock, R. C. J. Org. Chem. 2004, 69, 8251. The
corresponding 1,4-Rh migration has scarcely been utilized. See: (e)
Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem. Soc. 2000,
122, 10464. (f) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J.
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H.; Murakami, M. J. Am. Chem. Soc. 2005, 127, 1390.
1:1 mixture of deuterium-labeled 1a (1a-d) and unlabeled 1c was
treated with a catalytic amount of [Rh(cod)2](BF4) and P(p-tolyl)3
at room temperature, no deuterium was incorporated to 2c.
These results indicated that the reaction proceeded as designed
in the beginning (Scheme 1), and importantly, hydrorhodation of
the alkynyl ketone intermediate B′ occurred without dissociation
of the Rh-hydride complex to produce alkenyl rhodium complex
C′ directly (Scheme 3).
(8) For a review of Rh(I)-catalyzed reactions involving 1,4-addition of aryl
rhodium species, see: (a) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103,
169. See also: (b) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829.
(9) When RuCl2(PPh3)2 or [Ir(cod)2](BF4) + P(p-tolyl)3 or PtCl2(cod)2 + P(p-
tolyl)3 was used instead of [Rh(cod)2](BF4) + P(p-toyl)3, oxidation of
alcoholic substrate 1 was observed.
(10) The TMS group of the cyclized products 2i-2k were readily desilylated
under the reaction conditions.
(11) When TMP was employed as a base, a substantial amount of proton was
incorporated to the R-position of the carbonyl. We believe that the proton
comes from N-H of TMP via enolization under basic conditions.
In summary, we have developed a concise method for the
construction of a cyclopentanone ring based on hydrorhodation-
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