5500
G. Le Bras et al. / Tetrahedron Letters 47 (2006) 5497–5501
O
PTSA, EtOH
R
R
R
MWI, 170 °C
O
OCH3
OCH3
1t R = H
1u R = CH3
3t 39%
3u 63%
2t 58%
2u 14%
EtOMe
H+
R
R
O
O
CH3
CH3
EtOH
Scheme 1. Hydration of ortho-methoxydiarylalkynes 1 under microwaves irradiation: a plausible explanation of 2-arylbenzo[b]furans 3 formation.
and 1q efficiently reacted to give their corresponding
ketones with similar yields (entries 11 and 12). Surpri-
singly, the 3,4,5-trimethoxyaryl unit, which is frequently
found in natural substances,11 was found to disable the
triple bond. To circumvent this, the reactional tempera-
ture was increased to 170 ꢁC for 30 min (conditions C)
and ketones 2r and 2s were regioselectivity obtained in
good yields (entries 13 and 14).
starting from diarylalkynes with good outputs and by
preserving some various functional groups. The experi-
mental microwave experiments13 described in this letter
are well established and controlled to be safely and
beneficially reported.
Acknowledgements
Next, we studied the hydration of hindered diarylalky-
nes bearing in the ortho position a methoxy substituent
(Scheme 1). Surprisingly, hydration of 1t under condi-
tions B afforded beside the expected arylketone 2t
(58%) a 39% yield of 2-phenylbenzo[b]furan 3t. More
interestingly, under these conditions, the ortho meth-
oxytolylalkyne 1u reacted to mainly give the 2-substi-
tuted benzo[b]furan 3u (63%), together with a small
amount (14%) of arylketone 2u (Scheme 1). A plausible
explanation for the obtention of 2-arylbenzo[b]furans 3
(unoptimized in the present study) is depicted in Scheme
1. The 2-arylbenzo[b]furan 3 formation could not be ex-
plained by the well known12 intramolecular cyclization
of 2-alkynylphenol derivatives. Indeed we never ob-
served during this study any phenol formation resulting
from the methoxy cleavage even at higher temperatures
(see Table 2, entries 13 and 14), and 4-methylanisole
itself did not react under these conditions.
The CNRS is gratefully acknowledged for financial
support of this research. We wish to thank also ADIR
(Servier Group) for a doctoral fellowship to G.L.B.
Supplementary data
Supplementary data associated with this article can be
References and notes
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In summary, the purpose of this study was to expand the
chemistry scope of the hydration of arylalkylalkynes as
well as diarylalkynes under MWI. We have demon-
strated the positive effect of the microwaves heating
towards arylpropargylic alcohols, which could be
hydrated with reduced reaction times (50 times faster
than with conventional heating) under PTSA-catalysis.
Furthermore, the present process was extended to
the synthesis of various functionalized diarylketones