Highly selective 1,6-addition of aryl boronic acids to α,β, γ,δ-unsaturated carbonyl compounds catalyzed by an indium complex

Article abstract of DOI:10.1002/anie.200601719

(Chemical Equation Presented) Perfect control: The catalytic 1,6-addition of aryl boronic acids to electron-deficient dienes was realized by use of an iridium catalyst (see scheme). High yields of the corresponding δ-arylated carbonyl compounds were obtai

Full text of DOI:10.1002/anie.200601719

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Regioselectivity
cyclooctadiene),[7] efficiently catalyzes the addition to
simple dienones with perfect 1,6-regioselectivity. Thus, treat-
ment of (3E,5E)-3,5-heptadien-2-one (1) with phenylborox-
ine (1.0 equiv)[8] in the presence of a catalytic amount of
[{Ir(OH)(cod)}2] (5 mol% Ir) and H2O (0.5 equiv relative to
B) in toluene at 808C for 3 h gave a mixture of 1,6-adducts, 6-
phenylhepten-2-ones 2,[5] in 88% yield (Scheme 2). The
DOI: 10.1002/anie.200601719
Highly Selective 1,6-Addition of Aryl Boronic
Acids to a,b,g,d-Unsaturated Carbonyl
Compounds Catalyzed by an Iridium Complex**
Takahiro Nishimura, Yuichi Yasuhara, and
Tamio Hayashi*
The transition-metal-catalyzed 1,4-addition of organometallic
reagents to electron-deficient olefins is one of the most
reliable methods for selective C C bond formation,[1] but, on
À
the contrary, there is considerable difficulty in controlling the
regioselectivity of the addition to extended conjugate sys-
tems; for example, 1,6- or 1,4-addition to electron-deficient
dienes (Scheme 1). In this field of research, in which copper
Scheme 2. Iridium-catalyzed 1,6-addition of phenylboronic acid to
dienone 1.
mixture consists of (Z)-6-phenyl-4-hepten-2-one (2a) as the
major isomer (93%), its E isomer 2b (2%), and conjugate
ketone 2c (5%). The formation of the 1,4-addition product 3
was not detected at all under the present reaction conditions.
The formation of a small amount of diphenylation product 4
(2%), probably formed by the 1,4-addition of phenylboronic
acid to the conjugate ketone 2c, was also observed.
Scheme 1. 1,6-Addition versus 1,4-addition in a,b,g,d-unsaturated car-
bonyl compounds.
salts have been mainly used as the active catalysts,[1e,2]
Fukuhara and Urabe recently reported notable 1,6-selectivity
with iron as a catalyst in the addition of aryl Grignard
reagents to 2,4-dienoates and -dienamides.[3] Although rho-
dium-catalyzed conjugate addition has been developing very
rapidly,[4] only a few reports have appeared that describe 1,6-
or 1,4-selectivity in the addition to electron-deficient
dienes.[5,6] High 1,6-selectivity in the rhodium-catalyzed
reactions has been reported for a limited combination of
substrates: Examples include the addition of aryl zinc
reagents to dienones with b-substituents[5] and the addition
of aryl and alkenyl boronic acids to d-unsubstituted dien-
oates.[6] Herein, we report perfect 1,6-selectivity in the
addition of aryl boronic acids to a standard type of a,b,g,d-
unsaturated carbonyl compound, realized by use of an iridium
complex as a catalyst.
Although rhodium catalysts have been often used for the
addition of aryl metal reagents to electron-deficient alkenes,[4]
the iridium catalyst system employed in this addition has not
been well demonstrated so far. As a related reaction, Mori
and co-workers reported the first example of the iridium-
catalyzed addition/elimination reaction of aryl silicon
reagents with acrylates to give Mizoroki–Heck-type prod-
ucts.[9] To the best of our knowledge, the present 1,6-addition
is the first example of an iridium-catalyzed addition of aryl
boronic acids to electron-deficient alkenes or dienes.[10] The
unique 1,6-selectivity observed in the iridium-catalyzed
addition is made clear by comparison with the result obtained
with [{Rh(OH)(cod)}2][11] as a catalyst under the same
reaction conditions (Scheme 3). The rhodium-catalyzed reac-
tion gave the 1,4-adduct 3 as the main isomer (55% yield) and
a minor amount (34% yield) of 1,6-adducts 2a and 2b.
Competition experiments with a 1:1 mixture of dienone 1
and 3-penten-2-one (5) gave us insight into the origin of the
difference in regioselectivity between the iridium and rho-
dium catalysts in the addition of phenylboronic acid to the
dienone (Scheme 4). Thus, in the reaction of a 1:1 mixture of 1
During our efforts to realize the 1,6-addition of aryl
boronic acids to a,b,g,d-unsaturated carbonyl compounds, we
found that an iridium complex, [{Ir(OH)(cod)}2] (cod =
[*] Dr. T. Nishimura, Y. Yasuhara, Prof. T. Hayashi
Department of Chemistry
Graduate School of Science
Sakyo, Kyoto 606–8502 (Japan)
Fax: (+81)75-753-3988
E-mail: thayashi@kuchem.kyoto-u.ac.jp
[**] This work has been supported in part by a Grant-in-Aid for Scientific
Research, the Ministry of Education, Culture, Sports, Science and
Technology, Japan (Priority Areas “Advanced Molecular Transfor-
mations of Carbon Resources”).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or fromthe author.
Scheme 3. Rhodium-catalyzed addition of phenylboronic acid to dien-
one 1.
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Table 1: Iridium-catalyzed 1,6-addition to dienes.[a]
Entry
Diene
Ar
Yield [%][b]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
7
8
9
Ph
86 (11)[c]
82 (12)[c]
88 (13)[c]
75 (14)
84 (15)[c]
86 (16)
86 (17)
94 (18)
82 (19)
90 (20)
4-MeC6H4
4-MeOC6H4
4-CF3C6H4
4-FC6H4
2-naphthyl
Ph
Ph
Ph
Ph
10
10
Scheme 4. Competitive reaction of dienone 1 and enone 5 with phenyl-
boronic acid in the presence of [{Ir(OH)(cod)}2] or [{Rh(OH)(cod)}2].
[a] Reaction conditions: [{Ir(OH)(cod)}2] (0.025 mmol Ir), diene
(0.50 mmol), (ArBO)3 (0.50 mmol), H2O (0.75 mmol), toluene
(1.0 mL), 808C, 3 h. After short column chromatography on silica gel,
the products were subjected to hydrogenation in the presence of Pd/C
(10 mol%) under H2 (1 atm). [b] Yield of the isolated products. [c] A
diarylation product was also obtained in 2% yield in each case.
and 5 with phenylboronic acid in the presence of [{Ir(OH)-
(cod)}2], dienone 1 was consumed exclusively to give the 1,6-
adducts 2 (65%), thus leaving enone 5 unreacted. These
results indicate that the iridium catalyst has much a stronger
reactivity toward the dienone than enone. On the other hand,
the competition experiment with [{Rh(OH)(cod)}2] as a
catalyst gave a high yield (77%) of 4-phenyl-2-butanone
(6), which is the 1,4-addition product of enone 5, and a small
amount of 2 (6%) and 3 (9%), the addition products of the
dienone 1.
catalyzed hydroarylation were subjected to palladium-cata-
lyzed hydrogenation to give saturated ketones (Scheme 6).
On the basis of the high reactivity toward the diene
moiety and the high Z selectivity in the 1,6-addition product,
the catalytic cycle of the present iridium-catalyzed reaction is
speculated as shown in Scheme 5. Transmetalation of a phenyl
Scheme 6. Iridium-catalyzed 1,6-addition of aryl boronic acids to
electron-deficient dienes.
The reaction of dienone 1 with several aryl boronic acids with
electron-donating and -withdrawing substituents on the
benzene ring gave the corresponding d-aryl ketones in high
yields (75–88% yields, entries 1–6) after hydrogenation. The
1,4-addition to dienone 1 was not detected in any case. The
1,6-selectivity was also observed in the addition to dienones 7
(R1 = Me, R2 = Bu) and 8 (R1 = tBu, R2 = Me; entries 7 and 8,
respectively). This iridium-catalyzed reaction can be applied
to a,b,g,d-unsaturated ester 9 and amide 10 to give the
corresponding 1,6-addition products in 82 and 90% yield,
respectively (entries 9 and 10).
Scheme 5. Proposed catalytic cycle of the iridium-catalyzed 1,6-addi-
tion of phenylboronic acid to enone 1.
groupfrom the boron to iridium center forms a phenyl–
iridium species II.[9,12] The coordination of the dienone to the
phenyl–iridium complex with a cisoid diene moiety results in
the formation of a (h4-diene)–iridium complex III.[13] Inser-
tion of the diene into the phenyl–iridium bond, thus forming
p-allyl–iridium moiety IV,[14] followed by subsequent hydrol-
ysis with the assistance of phenylboronic acid or boric acid
gives the 1,6-addition product 2a with Z configuration and
the hydroxo–iridium species I. The selective incorporation of
deuterium at the a-position in [D]2a was observed in the
addition to dienone 1 by using D2O in place of H2O, which
aids the hydrolysis stepof p-allyl–iridium complex IV and
gives 2a.
In summary, the catalytic 1,6-addition of aryl boronic
acids to electron-deficient dienes was realized by use of an
iridium catalyst, which gave high yields of the corresponding
d-arylated carbonyl compounds with perfect 1,6-selectivity.
Experimental Section
(3E,5E)-3,5-Heptadien-2-one (1; 55.1 mg, 0.50 mmol) and H2O
(13.5 mL, 0.75 mmol) were added to a solution of [{Ir(OH)(cod)}2]
(8.3 mg, 0.025 mmol Ir) and phenylboroxine (156 mg, 0.50 mmol) in
toluene (1.0 mL) at room temperature. The reaction mixture was
heated at 808C for 3 h. After the usual workup, column chromatog-
raphy on silica gel gave a mixture of the 1,6-addition products. The
mixture was hydrogenated in the presence of Pd/C (10 mol% Pd)
The results of the 1,6-addition of aryl boronic acids to
a,b,g,d-unsaturated carbonyl compounds are summarized in
Table 1. The addition products provided by the iridium-
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Communications
under H2 (1 atm) in EtOAc (2.0 mL) at room temperature for 3 h to
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Received: May 2, 2006
Published online: July 3, 2006
Keywords: 1,6-addition · arylation · boronic acids · iridium·
.
regioselectivity
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