Tandem catalysis: Alcohol oxidation and C-C bond formation via Ci-H bond activation

Article abstract of DOI:10.1002/adsc.201000884

A tandem process involving oxidation of a benzylic alcohol functionality followed by hydroarylation is described. These two atom-economic sequences are very convenient to access functionalized aromatic ketones, using simple ruthenium trichloride as cataly

Full text of DOI:10.1002/adsc.201000884

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DOI: 10.1002/adsc.201000884
À
Tandem Catalysis: Alcohol Oxidation and C C Bond Formation
À
via C H Bond Activation
Marc-Olivier Simon,a Gaꢀl Ung,a and Sylvain Darsesa,*
a
Laboratoire Charles Friedel (UMR 7223, CNRS), Ecole Nationale Supꢁrieure de Chimie de Paris, 11 rue P&M Curie,
75231 Paris cedex 05, France
Fax : (+33)-1-4407-1062; e-mail: sylvain-darses@chimie-paristech.fr
Received: November 24, 2010; Revised: February 24, 2011; Published online: April 28, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000884.
À
Abstract: A tandem process involving oxidation of
a benzylic alcohol functionality followed by hydro-
arylation is described. These two atom-economic se-
quences are very convenient to access functional-
ized aromatic ketones, using simple ruthenium tri-
chloride as catalyst precursor. Moreover they
appear to be highly compatible, tolerant, and selec-
tive toward various functional groups, and the ease
of the protocol should make it very convenient for
synthetic purposes.
C H bond activation have been described in the liter-
ature,[6,7] and only one example has appeared of a
tandem reaction involving oxidation/hydroaryla-
tion.[8,9,10]
We report here a tandem catalytic reaction allowing
the selective functionalization of the ortho-position of
benzylic alcohols, via the hydride transfer oxidation
of the alcohol into a keto functionality,[11] followed by
À
À
C C bond formation via C H activation (Scheme 1).
À
Keywords: alcohols; arylation; C H activation; oxi-
dation; ruthenium
Scheme 1. Tandem oxidation/hydroarylation.
À
To develop environmentally friendly processes for C
C bond formation, much attention has been paid to
We previously reported highly convenient condi-
green and sustainable reactions. Among them, catalyt- tions for the hydroarylation of alkenes using aceto-
À
ic reactions involving C H bond activation are highly phenones as reagents and simple ruthenium chloride
desirable, not only because they allow the functionali- as catalyst precursor.[12,13] We wondered if this catalyst
À
zation of more easily available starting materials system would not only effect C H bond activation
(atom economy concept[1]) but also because they pro- but also alcohol oxidation via hydride transfer, as
duce clean reactions (reduced amounts of salts).[2] In many ruthenium catalyst can do.[7]
À
À
the field of C C bond formation via C H activa-
We were pleased to find that, using our previously
tion,[2] several catalytic reactions have been recently published conditions[13] namely ruthenium trichloride
developed,[3] and hydroarylation reactions, allowing as catalyst precursor, and simply by adding acetone as
the functionalization of alkenes with a total atom hydride acceptor, the reaction of 1-phenylethan-1-ol
economy, appear quite promising.[2,4]
(1a) with vinyltriisopropylsilane afforded a nearly
Another point of concern is the development of quantitative yield of ketone 3a (Table 1, entry 1).
“one-pot” tandem or domino processes involving mul- These conditions proved to be quite general as a large
tiple catalytic transformations, ideally using a single variety of benzyl alcohols could be easily functional-
catalyst, avoiding multiple work-up stages and allow- ized by this tandem reaction (Table 1).
ing minimization of wastes.[5] Indeed, catalytic tandem
Indeed, cyclohexylACTHNGUTERNNU(G phenyl)methanol (1b) is con-
À
reactions involving multiple C H bond activations, verted into the corresponding alkylated ketone 3b
that are combining these two concepts, would be with an 82% yield (entry 2). When the aromatic ring
highly desirable. But, to the best of our knowledge, is substituted by an ortho-methyl group, the oxida-
only a limited number of tandem reactions involving tion/hydroarylation products 3c and 3d were isolated
Adv. Synth. Catal. 2011, 353, 1045 – 1048
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Marc-Olivier Simon et al.
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Table 1. Tandem oxidation/hydroarylation.[a]
reacted equally well (entries 5–7), affording the ex-
pected alkylated ketones in 63–80% yield. Dialkyla-
tion products are generally obtained as major prod-
ucts because of the excess of vinylsilane and the long
reaction time. The reaction of 1-(2,3-dihydro-1,4-ben-
zodioxin-6-yl)ethanol (1h) leads exclusively to the for-
mation of the monoalkylated product 3h on the more
crowded position (5 position) because of possible che-
lation of the meta-oxygen atom to the ruthenium
complex (entry 8).[13] Similarly, 1-(naphthalen-2-yl)-
Entry Ar
R
Yield[b] [%] Mono/di[c]
AHCTUNGTREGeNNUN thanol (1i) leads to the formation of a single regio-
1
2
3
4
5
6
7
Ph
Ph
Me
Cy
Me
98 (3a)
82 (3b)
88 (3c)
63:37
50:50
isomer, the monoalkylated product in position 1, 3i
being the only compound obtained (entry 9). This re-
action has also been successfully conducted on heter-
oaryl alcohol substrates (entries 13–15). Thus, furan,
thiophene and indole nuclei (protected by a tert-butyl-
2-MeC6H4
2-MeC6H4
4-FC6H4
4-CF3C6H4
4-MeOC6H4
n-Bu 85 (3d)
Me
Me
Me
80 (3e)
63 (3f)
69 (3g)
8:92
8:92
0:100
AHCTUNGTREGoNNUN xycarbonyl) were easily functionalized to produce
the desired tandem oxidation/hydroarylation products
with yields ranging from 68 to 70%.
8
Me
Me
68[d] (3h)
100:0[e]
100:0[f]
In order to get some insights into the reaction
mechanism, some experiments were conducted. First
of all, it should be pointed out that the conversion of
the reaction is low when acetone is removed as co-sol-
vent. To elucidate the way the alcohol is oxidized and
the role of acetone, deuterium labelling studies were
conducted. Under the previous conditions, the reac-
tion of deuteriated carbinol 1a-d was monitored by
9
2-naphthyl
1-naphthyl
96 (3i)
10
11
12
n-Bu 89 (3j)
87 (3k)
76 (3kꢀ)[d,g]
13
14
2-furyl
2-thienyl
n-Bu 69 (3l)
Me
2
2
1H and H NMR (Scheme 2). The H NMR spectra of
the reaction mixture revealed the formation of 2-deu-
teriopropan-2-ol (d=3.64 ppm), formed by the reduc-
tion of acetone by a deuterioruthenium species. But
we also observed the formation of deuterioethyl-
70 (3m)
15
Me
68 (3n)
AHCTUNGTREG(NNUN triethyl)silane, where deuterium incorporation was
[a]
Reaction conducted using 0.5 mmol of 1, 1.5 mmol of 2,
RuCl3·xH2O 4 mol%, HCO2Na 30 mol%, (4-CF3C6H4)3P
15 mol% in 0.5 mL dioxane/acetone (1:1) at 1008C for
22 h.
Yields of mono- and di-substituted adducts.
Proportion of mono-/di-substituted adducts for 4-substi-
tuted substrates, and selectivity for 6- and 2-substituted
either observed in position 1 or 2. Indeed, it appeared
that the vinylsilane and the acetone are both acting as
hydride acceptors under these reaction conditions.[14]
The following mechanism can be proposed for this
tandem oxidation/hydroarylation reaction (Scheme 3).
The in situ generated ruthenium(0) can oxidatively
À
[b]
[c]
products for 3-substituted substrates determined by GC add into the O H bond of the starting alcohol to
1
form a hydridoACTHNUTRGNEUNG
(alkoxy)ruthenium species,[15] leading,
and H NMR.
[d]
[e]
40 h reaction.
The regioisomer alkylated in the 5 position was the only
product obtained.
The regioisomer alkylated in the 1 position was the only
product obtained.
[f]
[g]
Reaction conducted using trimethylvinylsilane.
with 88% and 85% yields, respectively, for arylmetha-
nols functionalized by a methyl, n-butyl or chain (en-
tries 3 and 4). In the latter case, the yield is even
higher than the one that had been obtained starting
directly from the corresponding acetophenone
(67%).[13] The reaction course does not seem to be in-
fluenced by the electronic properties of the substitu-
ents on the aromatic ring, as carbinols bearing elec-
tron-releasing or electron-withdrawing substituents Scheme 2. About the hydride acceptor.
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Adv. Synth. Catal. 2011, 353, 1045 – 1048

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À
Tandem Catalysis: Alcohol Oxidation and C C Bond Formation via C H Bond Activation
Scheme 3. Proposed reaction mechanism.
after b-H elimination, to acetophenone and generat- analysis). After concentration under reduced pressure, the
crude mixture was purified by silica gel chromatography.
ing a ruthenium dihydride (cycle 1). The latter can
then react with the hydride acceptor (acetone or vi-
nylsilane) to regenerate an active ruthenium(0) spe-
cies.[16] The hydroarylation of acetophenone (cycle 2)
then occurs as describe in the literature and involves
Acknowledgements
À
directed oxidative addition into the C H bond fol-
M.-O. Simon thanks the Ministꢀre de l’Education et de la Re-
cherche for a grant.
À
lowed by the insertion of the olefin into the Ru H
bond and by reductive elimination.
We have thus described an unusual tandem process
involving oxidation of an alcohol functionality fol-
lowed by a hydroarylation process. Reaction condi-
tions are very simple, using simple ruthenium trichlor-
ide as catalyst precursor and acetone as co-solvent.
Moreover they appear to be highly compatible, toler-
ant, and selective toward various functional groups,
and the ease of the protocol should make it very con-
venient for synthetic purposes.
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