Recently, we reported a novel transformation leading
to the formation of a rare heterocyclic motif, the (Z)-
chloromethylene ketal15 substructure 9 (Scheme 2). Thus,
addition of t-BuOK to dichloroethylene 8 leads rapidly to
the formation of the acetylenide anion 10, which adds to
the ketone 7 to afford the adduct 11. Condensation of 11
with a second equivalent of ketone produces the hemi-
ketal alkoxide 12 that undergoes an irreversible 5-exo-dig
cyclization, culminating in the obtention of the geome-
trically pure chloromethylene ketal 9.
Repeating the experiment but obviating the purifica-
tion step afforded the expected chloroacetylene addition
product 15 in essentially quantitative yields. This inter-
mediate could be isolated and characterized by NMR
after workup. However, its lifetime, even in a pure phase,
is too short for fully detailed analyses. Submitting 15 to
silica gel treatment smoothly gave rise to aldehyde 14 in
85% yield. These experiments strongly suggest that 15 is
the likely precursor of 14. A plausible mechanism is
depicted in Scheme 4.
Scheme 2
Scheme 4
Protonation of 15 by the acidic silica generates the
hydronium cation 16 which loses a water molecule, lead-
ing to the oxonium species 17. Conjugate addition of
water at the terminal position provides, after loss of a
proton, the R-chlorohydroxybenzofuran 18. Sponta-
neous elimination of HCl finally yields aldehyde 14.
While the silica gel treatment proved to be efficient in
some cases, it was not generally applicable. Therefore, the
acid-catalyzed rearrangementÀhydrolysis step was sub-
sequently performed using sulfuric acid in the biphasic
system16 H2O/CH2Cl2. Under these conditions, a variety
of commercially available o-hydroxyphenones were suc-
cessfully transformed into the corresponding benzofur-
ans in 59À97% isolated yield. Some pertinent examples
are collected in Table 1.
In an attempt to further broaden the scope of this
condensation, ketone 13 was employed as the substrate.
Much to our surprise, benzofuran carbaldehyde 14 was
obtained in excellent yield after purification of the crude
product by silica gel column chromatography (Scheme 3).
Scheme 3
As can be seen from Table 1, the reaction proves to be
quite general and high yielding, proceeding efficiently
with both alkyl- and aryl-substituted phenones (entries
1À5). It tolerates various substituents, including halides
(entries 2 and 3) and methoxy group (entries 6 and 7).
A limitation of the tert-butoxide-based protocol was
uncovered when aromatic aldehydes were used as sub-
strates. In these cases, a rapid degradation of the reaction
mixture was observed. Therefore, it was decided to mod-
ify our procedure, and LDA, instead of t-BuOK, was
employed to prepare the chloroacetylene anion. Drop-
wise addition of salicylaldehyde 28 to the lithiated alkyne,
followed by the usual acid-catalyzed rearrangement,
^
(9) Amatore, C.; Blart, E.; Genet, J. P.; Jutand, A.; Lemaire-Audoire,
S.; Savignac, M. J. Org. Chem. 1995, 60, 6829.
(10) Sogawa, A.; Tsukayama, M.; Nozaki, H.; Nakayama, M.
Heterocycles 1996, 43, 101.
(11) Cacchi, S.; Fabrizi, G.; Moro, L. Tetrahedron Lett. 1998, 39,
5101.
(14) Patel, V.; Pattenden, G.; Russell, J. Tetrahedron Lett. 1986, 27,
2303.
ꢀ
(12) Furstner, A.; Davies, P. J. Am. Chem. Soc. 2005, 127, 15024.
(13) Oppenheimer, J.; Johnson, W.; Tracey, M.; Hsung, R.; Yao,
P. Y.; Liu, R.; Zhao, K. Org. Lett. 2007, 9, 2361.
(15) Schevenels, F.; Marko, I. Chem. Commun. 2011, 47, 3287.
(16) When HCl was employed as the acid, fomation of the corre-
sponding dichloride was observed.
Org. Lett., Vol. 14, No. 5, 2012
1299
Schevenels, Florian
