Rhodium catalysed addition of boronic acids to anhydrides: A new method for the synthesis of ketones

Article abstract of DOI:10.1039/b107633g

The efficient transmetalation from boron to rhodium is exploited in a new synthesis of aryl and alkenyl ketones.

Full text of DOI:10.1039/b107633g

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Rhodium catalysed addition of boronic acids to anhydrides: a new
method for the synthesis of ketones
Christopher G. Frost* and Kelly J. Wadsworth
Department of Chemistry, University of Bath, Bath, UK BA2 7AY. E-mail: c.g.frost@bath.ac.uk;
Fax: 01225 826231; Tel: 01225 826142
Received (in Cambridge, UK) 22nd August 2001, Accepted 26th September 2001
First published as an Advance Article on the web 24th October 2001
The efficient transmetalation from boron to rhodium is
exploited in a new synthesis of aryl and alkenyl ketones.
To demonstrate this concept, initial experiments examined
the reaction of phenylboronic acid (1.6 equiv.) 1 with acetic
anhydride 2 in the presence of 5 mol% of various rhodium
complexes (Scheme 1).6 As summarised in Table 1, the
formation of acetophenone 3 is symptomatic of an effective
protocol for ketone synthesis.
The rhodium catalysed addition of boronic acids to organic
electrophiles has recently emerged as an important tool for
1
organic synthesis. An efficient transmetalation between boron
and rhodium permits the addition of organoboronic acids to a
The first point to note is that in the absence of catalyst no
product formation is observed. It was interesting to learn that the
Rh(acac) complexes favoured for addition to activated olefins,
were not particularly effective in this case (entries 2–7).
2
range of activated olefins. Significant advances have also been
made in the coupling of unactivated olefins in aqueous media.3
Further to this the addition of aryl boronic acids to aldehydes
and imines has been achieved.4 The mechanism of these
transformations is proposed to involve transmetalation between
Similarly, the use of [Rh(OAc)
disappointing results (entries 10 and 11). Gratifyingly, the use
of [Rh(alkene)Cl] complexes showed more promise (entry 9)
2 2 3 2
] and RhCl ·3H O afforded
the boronic acid and the rhodium(
I
) complex to afford an R–
2
Rh( ) species. The nucleophilic R group then adds to the
I
coordinated electrophile yielding either a Rh bound enolate or
alkoxide which is subsequently hydrolysed. As part of our
research programme developing catalysts for the functionalisa-
tion of aromatics, we were interested in the boron–rhodium
transmetalation process as a means to promote the equivalent of
a Friedel–Crafts acylation reaction of deactivated aryl deriva-
tives. This is a demanding transformation which is not readily
Table 2 Rhodium catalysed synthesis of ketones
Entry
Boronic acid
Product
Yield (%)
86
1
5
achieved by even the most effective Lewis acid catalysts. In
this communication we wish to report our development of an
efficient rhodium catalysed addition reaction that allows the
synthesis of ketones from boronic acids under mild condi-
tions.
2
3
68
67
4
5
56
54
Scheme 1 Rhodium catalysed acylation.
Table 1 Rhodium catalysed addition of 1 to acetic anhydride 2
Entry
Catalyst
Solvent (Temp./°C)
Yield of 3 (%)
6
7
76
70
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
—
Dioxane (100)
Dioxane (100)
0
0
0
16
18
27
29
20
57
27
0
83
84
17
37
85
[Rh(acac)(ethylene)
[Rh(acac)(ethylene)
[Rh(acac)(cod)]
[Rh(acac)(cod)]
[Rh(acac)(nbd)]
[Rh(acac)(nbd)]
[Rh(nbd)Cl]
[Rh(cod)Cl]
[Rh(OAc)
RhCl ·3H O
2
[Rh(ethylene)Cl]
[Rh(ethylene)Cl]
[Rh(ethylene)Cl]
[Rh(ethylene)Cl]
[Rh(ethylene)Cl]
[Rh(ethylene)Cl]
2
2
]
]
a
DME–H
Dioxane (100)
DME–H O (65)
Dioxane (100)
DME–H O (65)
2
O (65)
a
2
a
2
2
Dioxane (100)
Dioxane (100)
Dioxane (100)
Dioxane (100)
Dioxane (100)
2
8
9
88
1
1
1
1
1
1
1
1
a
2 2
]
3
2
2
2
2
2
2
a
DME–H
2
O (65)
Toluene (100)
THF (65)
DME (65)
DME (20)
59
74
b
c
76
1
0
DME–H
2
O (6+1). b Yield after 2 hours. c Yield after 16 hours.
2316
Chem. Commun., 2001, 2316–2317
DOI: 10.1039/b107633g
This journal is © The Royal Society of Chemistry 2001

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resulting in the formation of 3 in excellent overall yield in the
best case (entry 12). The choice of solvent had a clear effect on
the efficiency of the reaction (entries 12–16) with the reaction
proceeding smoothly in dioxane and 1,2-dimethoxyethane
This transformation proceeds in good yield for a range of
boronic acids. Importantly, this new methodology offers
specific advantages over traditional Lewis acid catalysed
acylation reactions in that it allows the regiospecific functional-
isation of activated, unactivated and deactivated aromatics.
C. G. F. thanks Astra-Zeneca for a generous award from their
strategic research fund.
(
(
DME). The insensitivity of this protocol towards air and water
entry 13) is extremely beneficial from a practical perspective.
At 65 °C in DME the reaction was complete within two hours,
whilst at room temperature the reaction required 24 hours to
afford comparable yields (entries 16 and 17). Furthermore, the
catalyst loading could be lowered to 1.5 mol% with the product
Notes and references
† General experimental procedure: to a pressure tube charged with
2
[Rh(ethylene)Cl] (0.006 mmol, 1.5 mol%) was added 1,4-dioxane (4 ml),
3
being obtained in an 87% yield after 16 hours. Upon lowering
to 0.1 mol% of catalyst, a modest 33% of 3 was isolated after the
same period of time.
Under the optimised conditions the reaction was examined
with respect to the scope of the boronic acid (Table 2).† An
attractive feature of this methodology is the commercial
availability of a wide range of boronic acids. An important point
to note about the presented reaction is the regiospecific
formation of product with the electrophile substituting the
boronic acid group. Therefore, whilst electronic effects (in-
ductive and resonance) may influence the rates of the reactions,
as a consequence of the nucleophilicity dictating the trans-
metalation and transfer processes, the composition of product is
unaffected by the nature and position of substituent in the
starting boronic acid. This offers a significant tactical advantage
over Lewis acid catalysed electrophilic substitution processes.
Thus, the reaction can be designed to mirror typical electro-
philic substitution reactions (Table 2, entry 3). Conversely, the
formation of meta- or para-substituted deactivated aromatics
can be achieved in excellent isolated yield (Table 2, entries 1, 2
and 4). The results also confirm the scope of the reaction with
the alternative electrophile, benzoic anhydride (Table 2, entries
boronic acid (0.56 mmol) and anydride (1 ml of 0.4 M solution). The tube
was sealed, placed in a cold oil bath which was then heated to the required
temperature and stirred for 16 hours. The mixture was allowed to cool to
room temperature then worked up by extracting with ethyl acetate, washing
with brine, drying over magnesium sulfate and concentrating in vacuo. The
crude product was then purified by flash chromatography (ethyl acetate–
hexane, 1+8 by volume). All the products have been satisfactorily
1
13
characterised by H NMR, C NMR and IR spectroscopy.
1 (a) M. Sakai, H. Hayashi and N. Miyaura, Organometallics, 1997, 16,
4229; (b) Y. Takaya, M. Osgawara, T. Hayashi, M. Sakai and N.
Miyaura, J. Am. Chem. Soc., 1998, 120, 5579; (c) S. Sakuma, M. Sakai,
R. Itooka and N. Miyaura, J. Org. Chem., 2000, 65, 5951; (d) T. Hayashi,
T. Senda, Y. Takaya and M. Ogasawara, J. Am. Chem. Soc., 2000, 122,
1
0716.
2
3
For an excellent review, see: T. Hayashi, Synlett, 2001, 879.
M. Lautens, A. Roy, K. Fukuoka, K. Fagnou and B. Martin-Matute, J.
Am. Chem. Soc., 2001, 123, 5358.
4 (a) M. Sakai, M. Ueda and N. Miyaura, Angew. Chem., Int. Ed., 1998, 37,
3279; (b) M. Ueda and N. Miyaura, J. Org. Chem., 2000, 65, 4450; (c) A.
Fürstner and H. Krause, Adv. Synth. Catal., 2001, 343, 343.
5
(a) Lewis Acids in Organic Synthesis, ed. H. Yamamoto, Wiley-VCH,
Weinheim, 2000; (b) C. J. Chapman, C. G. Frost, J. P. Hartley and A. J.
Whittle, Tetrahedron Lett., 2001, 42, 773.
6–10). Furthermore, the reaction can be extended to alke-
nylboronic acids with no significant loss in efficiency. At the
present time, difficulties have been encountered in extending
6
7
All rhodium salts were purchased (Aldrich, Strem) and used as
received.
For corresponding palladium catalysed protocol, see: (a) C. S. Cho, K.
Itotani and S. Uemura, J. Organomet. Chem., 1993, 433, 253; (b) N. A.
Bumagin and D. N. Korolev, Tetrahedron Lett., 1999, 40, 3057; (c) M.
Haddach and J. R. McCarthy, Tetrahedron Lett., 1999, 40, 3109.
7
the methodology to acid chlorides. Further investigations are
directed towards accomplishing this and the addition of
organoboronic acids to other electrophiles.
In summary, a new rhodium catalysed addition of boronic
acids has been developed that allows the synthesis of ketones.
Chem. Commun., 2001, 2316–2317
2317