Rhodium-catalyzed aryl transfer from trisubstituted aryl methanols to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1002/anie.200700902

(Chemical Equation Presented) A process of elimination: The rhodium-catalyzed arylation of α,β-unsaturated carbonyl compounds with 9-aryl-10-benzyl-9,10-dihydroacridin-9-ols 1 as arylating reagents proceeds efficiently via β-aryl elimination of the rhodium alkoxide intermediates, to give the 1,4-addition products in high yields (see scheme; Bn = benzyl, cod = cycloocta-1,5-diene).

Full text of DOI:10.1002/anie.200700902

Angewandte
Chemie
DOI: 10.1002/anie.200700902
b-Aryl Elimination
Rhodium-Catalyzed Aryl Transfer from Trisubstituted Aryl Methanols
to a,b-Unsaturated Carbonyl Compounds**
Takahiro Nishimura,* Taisuke Katoh, and Tamio Hayashi*
In transition-metal-catalyzed organic reactions involving
carbon–carbon bond formation, a carbon–metal catalyst
bond is often generated by transmetalation of the organic
group in an organometallic reagents. For example, in the
rhodium-catalyzed conjugate arylation of electron-deficient
alkenes, a wide variety of arylating reagents composed of B,
Si, Zn, Sn, and Ti have been used for the formation of aryl
rhodium intermediates by transmetalation (Scheme 1).[1] On
and co-workers, in which rhodium tert-alkoxide complexes
[Rh(OCR2Ph)(PEt3)3] generate the phenylrhodium complex
[RhPh(PEt3)3] and the corresponding ketones under mild
conditions.[8] During our efforts to realize catalytic organic
transformations utilizing the b-hydrocarbyl elimination pro-
cess on transition-metal alkoxides,[5b,6a–d] we found that the
acridinols 1 (Bn = benzyl), which are readily obtained by
Grignard addition to 10-benzylacridin-9(10H)-one (2), are
Scheme 1. Rhodium-catalyzed 1,4-addition of aryl organometallic
reagents.
highly reactive towards b-aryl elimination on their alkoxide
complexes. Herein, we describe the rhodium-catalyzed con-
jugate arylation of a,b-unsaturated carbonyl compounds with
the trisubstituted aryl methanols 1 as aryl transfer reagents.
In the first set of experiments, several types of a,a-
substituted benzylalcohols were examined for their reactivity
in the rhodium-catalyzed 1,4-addition to 3-nonen-2-one (3a;
Scheme 3, Table 1). In the presence of [{Rh(OH)(cod)}2]
(cod = cycloocta-1,5-diene) as a catalyst in toluene at 1108C
for 3 h, the starting enone 3a was recovered intact with 2-
phenyl-2-propanol (4m), triphenylmethanol (5m), and cyclic
alcohols 6m and 7m.[9] The reaction of xanthenol 8m, which
has been reported to be a good phenyl donor in the
palladium-catalyzed cross-coupling with aryl halides,[3a] gave
the 1,4-addition product 9am, but its yield was low (22%;
Table 1, entry 1). Acridinol 1m was found to be much more
reactive than the others towards the present rhodium-
catalyzed 1,4-addition to give 9am in quantitative yield
(Table 1, entry 2). The eliminated ketone, acridinone 2, was
recovered in high yield (86%).
the other hand, it has been recently reported that organo-
transition-metal species can be generated from metal alk-
oxides through b-hydrocarbyl elimination (Scheme 2) in some
catalytic organic transformations.[2–7]
Scheme 2. b-Hydrocarbyl elimination.
As for b-aryl group elimination, Miura and co-workers
disclosed that the palladium-catalyzed cross-coupling of aryl
halides to give biaryls proceeds with trisubstituted aryl
methanols as coupling partners.[3] They also reported the
palladium-catalyzed hydroarylation of enones with trisubsti-
tuted aryl methanols, although the reaction requires severe
reaction conditions (xylene, 1608C).[3c] Recently, stoichiomet-
ric b-phenyl elimination on rhodium was reported by Hartwig
[*] Dr. T. Nishimura, T. Katoh, Prof. T. Hayashi
Department of Chemistry
Graduate School of Science
Sakyo, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3988
E-mail: tnishi@kuchem.kyoto-u.ac.jp
thayashi@kuchem.kyoto-u.ac.jp
[**] This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science, and
Technology, Japan (Priority Areas “Advanced Molecular Transfor-
mations of Carbon Resources”).
Supportinginformation for this article is available on the WWW
under http://www.angewandte.org or from the author.
Scheme 3. Rhodium-catalyzed conjugate arylation of a,b-unsaturated
carbonyl compounds through b-aryl elimination.
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Table 1: Rhodium-catalyzed hydroarylation of a,b-unsaturated carbonyl
compounds through b-aryl elimination.[a]
example, the reaction of enone 3b with acridinol 1p
(5 mol% Rh of 10, in toluene at 1108C for 3 h) gave the
corresponding b-aryl ketone 9bp (68% yield, 77% ee).
The formation of a phenylrhodium species by phenyl
transfer from the acridinol was confirmed by 31P NMR studies
of a stoichiometric reaction of complex 10. Thus, treatment of
complex 10 with acridinol 1m in the presence of enone 3c and
PPh3 brought about the formation of two rhodium complexes
in a ratio of 6:4 (Scheme 5). The major complex, which shows
Entry
Alkene
Ar
Product
Yield[b]
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3c
3d
Ph (8m)
Ph (1m)
9am
9am
9an
9ao
9ap
9aq
9ar
– (22)
96 (99)
99
99
94
2-MeC6H4 (1n)
3-MeC6H4 (1o)
4-MeC6H4 (1p)
4-MeOC6H4 (1q)
3,4-(OCH2O)C6H3 (1r)
1-naphthyl (1 s)
4-ClC6H4 (1t)
4-CF3C6H4 (1u)
4-MeC6H4 (1p)
4-MeC6H4 (1p)
4-MeC6H4 (1p)
Ph (1m)
94
98
91
9as
9at
9[c]
10[c]
11
12
13[f]
14
91[d]
96[e]
99
9au
9bp
9cp
9cp
9dm
99
99
94
[a] Reaction conditions: alkene 3 (0.20 mmol), alcohol (0.22 mmol),
[{Rh(OH)(cod)}2] (5 mol% Rh), and toluene (1.0 mL) at 1108C for 3 h.
[b] Yield of isolated product. Values in parentheses are NMR yields.
[c] For 10 h. [d] 87% yield of 9at for 3 h. [e] 48% yield of 9au for 3 h.
[f] Performed with 1 mol% Rh for 6 h.
Scheme 5. Reaction of rhodium complex 10 with acridinol 1m.
three ddd multiplets at d = 29.5, 32.8, and 35.4 ppm,[13] was
assigned to be complex 11.[12] The minor complex, which was
formed as a sole product on heating complex 11 at 1108C for
24 h, was assigned to be the cyclometalated rhodium complex
12 by the similarity of its 31P NMR spectrum[14] to that of
[Rh(o-C6H4PPh2)(PPh3)2].[15] The formation of phenylrho-
dium complex 11 was not observed with the trisubstituted
phenylmethanols 7m or 8m under the same conditions (at
1108C for 2 h), which indicates that an efficient b-aryl
elimination that generates an aryl rhodium species is charac-
teristic of the alkoxorhodium intermediate derived from
acridinol 1.
A catalytic cycle of this process is illustrated in Scheme 6.
b-Aryl elimination of an alkoxorhodium intermediate B,
generated from the rhodium complex A and an acridinol 1,
results in an aryl rhodium species C. Insertion of the alkene
moiety into the aryl–rhodium bond in C, followed by ligand
exchange between the resulting oxa-p-allylrhodium inter-
mediate D[12] and the alcohol 1, gives the 1,4-addition product
and alkoxorhodium B, which carries the catalytic cycle
further.
Several trisubstituted aryl methanols[10] 1n–1u, which
bear different substituents on the benzene ring, were success-
fully applied to the conjugate arylation of enone 3a to give the
corresponding ketones 9an–9au in high yields (91–99%;
Table 1, entries 3–10). Although the transfer of aryl groups
with electron-withdrawing substituents (Cl and CF3) was
slower, high yields of the arylation products were obtained by
carrying out the reaction for a prolonged period of time
(Table 1, entries 9 and 10). The addition to a,b-unsaturated
ketones 3b and 3c and ester 3d also proceeded smoothly to
give the 1,4-addition products 9bp (99%), 9cp (99%), and
9dm (94%), respectively (Table 1, entries 11–14).
On the basis of the high catalytic activity of cod complex
[{Rh(OH)(cod)}2], as demonstrated in Table 1, chiral diene
ligands were tested for the asymmetric arylation by using the
present aryl transfer from acridinols. The use of (S,S)-Bn-
bod*[11] enabled the arylation to proceed with high enantio-
selectivity. Thus, the reaction of enone 3a with acridinol 1p in
the presence of Cs2CO3 and a chiral diene–rhodium catalyst,
generated in situ from [{RhCl(C2H4)2}2] and (S,S)-Bn-bod*, at
908C for 24 h gave the 1,4-addition product 9ap in 95% yield
and with an enantiomeric excess (ee) of 94% (Scheme 4).
The asymmetric aryl transfer reaction was also catalyzed
by bisphosphine–rhodium complex [{Rh(OH)((R)-binap)}2]
In summary, we have developed a rhodium-catalyzed
conjugate arylation of a,b-unsaturated carbonyl compounds
by use of trisubstituted aryl methanols derived from acridi-
none 2. The b-aryl elimination on an alkoxorhodium inter-
mediate, which is involved as a key step in the catalytic cycle,
(10;
binap = 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl),
which is known to be one of the best chiral catalysts for the
asymmetric 1,4-addition,[12] although its catalytic activity is
lower than that of the diene–rhodium complexes. For
Scheme 6. Proposed catalytic cycle of the rhodium-catalyzed 1,4-addi-
tion of acridinols 1 to enones 3.
Scheme 4. Asymmetric 1,4-addition to enone 3a.
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Chemie
Nishimura, H. Araki, Y. Maeda, S. Uemura, Org. Lett. 2003, 5,
2997; c) A. Funayama, T. Satoh, M. Miura, J. Am. Chem. Soc.
2005, 127, 15354.
was strongly dependent on the structure of the backbone of
the tertiary alcohol bearing the aryl group. Studies on some
other catalytic arylation reactions utilizing the trisubstituted
aryl methanols are under way.
[6] For examples of b-alkyl elimination of 1-substituted cyclobuta-
nols, see: a) T. Nishimura, K. Ohe, S. Uemura, J. Am. Chem. Soc.
1999, 121, 2645; b) T. Nishimura, S. Uemura, J. Am. Chem. Soc.
1999, 121, 11010; c) S. Matsumura, Y. Maeda, T. Nishimura, S.
Uemura, J. Am. Chem. Soc. 2003, 125, 8862; d) T. Nishimura, S.
Uemura, Synlett 2004, 201; e) T. Matsuda, M. Makino, M.
Murakami, Org. Lett. 2004, 6, 1257; f) T. Matsuda, M. Makino,
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[7] For an example of b-alkyl elimination through reductive
cleavage of a carbon–carbon bond, see: H. Harayama, T.
Kuroki, M. Kimura, S. Tanaka, Y. Tamaru, Angew. Chem.
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128, 3124.
Experimental Section
3-Nonen-2-one (3a; 28.0 mg, 0.20 mmol) was added to a mixture of
acridinol 1m (79.9 mg, 0.22 mmol) and [{Rh(OH)(cod)}2] (2.3 mg,
0.005 mmol) in toluene (1.0 mL), and the mixture was stirred at
1108C for 3 h under a N2 atmosphere. After cooling to room
temperature, the reaction mixture was passed through a short column
of silica gel with diethyl ether as eluent. After evaporation of the
solvent, the residue was subjected to preparative thin-layer chroma-
tography (hexane/ethyl acetate 10:1) to give 4-phenylnonan-2-one
(9am; 96% yield).
Received: February 28, 2007
Published online: May 16, 2007
[9] Catalytic or stoichiometric b-aryl elimination of metal alkoxides
of trisubstituted aryl methanols 4m–6m and 8m has been
known; see references [3a–c] and [8].
[10] The X-ray crystal structure of 1o is shown in Figure S1 in the
Supporting Information.
Keywords: 1,4-addition · aryl carbinols · arylation · elimination ·
rhodium
.
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[13] Complex 11: 31P NMR (C6D6): d = 29.5 (ddd, JP, P, trans = 324,
J
J
Rh,P = 178, JP, P,cis = 39 Hz), 32.8 (ddd, JP, P, trans = 324, JRh,P = 170,
P, P, cis = 30 Hz), 35.4 ppm (ddd, JRh,P = 121, JP, P,cis = 39, JP, P, cis
=
30 Hz).
[14] Complex 12: 31P NMR (C6D6): d = À50.0 (ddd, JP, P, trans = 320,
JRh,P = 113, JP, P, cis = 25 Hz), 38.4 (ddd, JRh,P = 118, JP, P, cis = 32,
JP, P, cis = 25 Hz), 44.5 ppm (ddd, JP, P, trans = 320, JRh,P = 185, JP, P, cis
=
32 Hz).
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