Formation and cleavage of C-H, C-C, and C-O bonds of ortho-methyl- substituted anisoles by late transition metals

Article abstract of DOI:10.1021/ja0586790

2,6-Dimethyl-substituted anisoles can be converted into the corresponding 2-ethyl-6-methylphenols in a several-step reaction mediated by a Tp^Me₂Ir(III) complex; use of the ¹³C-enriched anisoles, ArO¹³CH₃

Full text of DOI:10.1021/ja0586790

Published on Web 02/25/2006
Formation and Cleavage of C-H, C-C, and C-O Bonds of
ortho-Methyl-Substituted Anisoles by Late Transition Metals
†
,†
†
‡
†
Patricia Lara, Margarita Paneque,* Manuel L. Poveda, Ver o´ nica Salazar, Laura L. Santos, and
,
†
Ernesto Carmona*
Instituto de InVestigaciones Qu ´ı micas, Departamento de Qu ´ı mica Inorg a´ nica, CSIC, UniVersidad de SeVilla,
AVda. Am e´ rico Vespucio no 49, 41092 SeVilla, Spain, and CIQ, UniVersidad Aut o´ noma del Estado de Hidalgo,
Pachuca, Hidalgo, M e´ xico
Received December 22, 2005; E-mail: guzman@us.es; paneque@iiq.csic.es
Rearrangement of alkyl aryl ethers, ROAr, to alkyl phenols (eq
Scheme 1
1
) is an important reaction that occurs with (or without) various
1
Lewis acid catalysts. ortho-Substituted phenols are commonly
obtained (as in the Claisen rearrangement for R ) allyl ), but
1
3
blocking the o-positions with aliphatic groups (e.g., CH ) yields
usually the corresponding p-R-substituted phenols instead of those
resulting from aliphatic C-C coupling of the R group with one of
2
the o-substituents. Herein we wish to report the conversion of the
anisoles of Scheme 1 into the corresponding 2-ethyl-6-methyl-
phenols 2, through the intermediacy of the hydride aryloxide iridium
1
3
13
3
compounds 1. The use of the C-enriched anisoles, ArO CH ,
demonstrates that the 13C label distributes across the two olefinic
sites of compounds 1 and thereby across the two ethyl positions of
the phenols 2. Hence the irreversible cleavage of the unstrained
R-OAr bond3 is accompanied by multiple C-H bond activations
and by reversible and irreversible C-C and C-O bond forming
and breaking reactions.7
-6
-9
Scheme 2
Heating the anisoles 2,6-Me
in the presence of the unsaturated species [Tp
2
C
6
H
3
OMe and 2,4,6-Me
3
C
6
H
2
OMe
Me
]10 gives
2
Ir(C H )
6 5 2
compounds 1a and 1b, respectively, in spectroscopic yields close
1
to 90%. These compounds feature a characteristic high-field H
1
13
NMR resonance around δ -17.5 ppm, whereas the H and C-
{
1
H} NMR data for their olefinic ligands are very similar to those
found for an analogous complex generated in the reaction of 2-ethyl-
11a
phenol with the same Ir(III) precursor. Obtention of phenols 2a
and 2b from 1a and 1b, respectively, can be achieved by treatment
Me
11b
with SiHEt
3
under 4 atm of H
2
to yield Tp
2
(H)
3
(SiEt
3
)
along
with the corresponding silyl ethers, which are then easily hydrolyzed
to the phenols 2. The reaction steps of Scheme 1 can be effected
sequentially without isolating the intermediate products.
To gain mechanistic insight into this complex transformation,
Even though analytically pure samples of 3a and 4a have not
Me
the reaction of Tp
2
Ir(C
6
H
5
)
2
(N
2
) and 2,6-dimethylanisole has been
12, Ar atmosphere).
been obtained (contamination by minor amounts of the other
carbene intermediate and the hydride alkene product was unavoid-
able), the structural characterization of the two compounds by 1D
and 2D NMR techniques is unambiguous (see Supporting Informa-
tion). Their formation can be proposed to take place as depicted in
Scheme 2 for the 2,6-dimethylanisole reaction. Following initial
1
6
monitored by H NMR spectroscopy (60 °C, C D
Two hydride carbene intermediates can be detected (Scheme 2)
and are characterized by 1H carbene and hydride resonances,
respectively, at 15.49 and -15.06 ppm (3a) and 15.75 and -17.03
ppm (4a). Further heating results in the progressive disappearance
of the signals due to 3a and the emergence of resonances
corresponding to the reaction product 1a. The NMR monitoring
reveals conclusively that 3a converts into 4a which then rearranges
to 1a without any other observable intermediate. 2,4,6-Trimethyl-
anisole exhibits an almost identical behavior.
3
sp C-H bond activation within the -OMe unit, reversible R-H
12
elimination would give the hydride carbene 3a, whereas a second
3
sp C-H bond activation, this time involving one of the ortho-Me
groups of the anisole, along with another reversible R-H elimination
step would account for the formation of the second intermediate
13
†
4a. The isomeric hydride alkylidene resulting from R-H elimina-
tion from the other Ir-CH unit of B has not been detected. Similar
CSIC and Universidad de Sevilla.
Universidad Aut o´ noma del Estado de Hidalgo.
‡
2
3512
9
J. AM. CHEM. SOC. 2006, 128, 3512-3513
10.1021/ja0586790 CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
CTQ 2004-00409/BQU, FEDER support), the Junta de Andaluc ´ı a,
and cooperation project CSIC-CONACyT are gratefully acknowl-
edged. L.L.S. and P.L. thank the MEC for research grants.
Supporting Information Available: Synthetic procedures and
spectroscopic and analytical data for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
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1
3
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9
a,c,d,17,18
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,16
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Acknowledgment. Dedicated to Prof. Victor Riera on the
occasion of his retirement. Financial support from the DGI (Project
JA0586790
J. AM. CHEM. SOC.
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VOL. 128, NO. 11, 2006 3513