C. Noonan et al. / Tetrahedron Letters 49 (2008) 4003–4006
4005
donating or electron withdrawing substituents were found
to be compatible with the methodology at ambient temper-
ature (entries 1, 3 and 5–8)—only the strongly deactivated
substrates 14 and 16 required elevated temperatures of
of related synthetically useful coupling processes using
alternative nucleophiles. Investigations along these lines
are currently underway in our laboratory.
4
0–60 °C (entries 2 and 4). Interestingly, o-substituted
aldehydes provided the corresponding methyl esters in
reproducibly) higher yields than their p-substituted
Acknowledgements
(
Financial support from Science Foundation Ireland
counterparts, the reason for which is unclear at this time.
Cinnamaldehyde (18) and 2-naphthaldehyde (19) could
also be esterified under the influence of thiazolium ion
catalysis, however, aliphatic aldehydes such as hexanal
(SFI) and Trinity College Dublin is gratefully
acknowledged.
References and notes
(
20) proved problematic, furnishing 28 in low yield.
The use of alternative alcohol nucleophiles was also
1
. (a) Otera, J. Esterification: Methods, Reactions and Applications;
Wiley: New York, 2003; (b) Larock, R. C. Comprehensive Organic
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investigated. We were pleased to find that the oxidative
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isopropanol could be smoothly coupled with benzaldehyde
2
. Representative recent examples: (a) Lerebours, R.; Wolf, C. J. Am.
Chem. Soc. 2006, 128, 13052; (b) Yoo, W.-J. ; Li, C.-J. J. Org. Chem.
1
7
to give 29 in good yield at ambient temperature. Synthet-
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be similarly prepared (Table 3).
2
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In summary, we have studied the oxidative esterification
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1
8
conditions were identified under which aromatic and a,b-
unsaturated aldehydes could be coupled efficiently with
either a primary or secondary alcohol in the presence of
a stoichiometric oxidant. Both activated and deactivated
aldehydes can be esterified, however aliphatic aldehydes
give poor results. Thiazolium catalysts proved superior to
their triazolium analogues and can be employed at low
loadings in conjunction with a single equivalent of the alco-
hol nucleophile at ambient temperature for the first time.
We would contend that this convenient methodology rep-
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1
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3
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1
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1
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ROH (1.0 equiv.)
THF (3.0 M)
O
O
9
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Ph
12 (1.0 equiv.)
Ph
OR
8
a (10 mol%)
3
NEt (7.5 mol%)
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a
Entry
1
Product
Yield (%)
O
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1
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O
87
1
503.
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b) White, F. G.; Ingraham, L. L. J. Am. Chem. Soc. 1962, 84,
109.
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2
9
1
(
3
O
O
2
O
76
55
‘
3
0
2
Am. Chem. Soc. 2004, 126, 9519; (c) Burstein, C.; Glorius, F. Angew.
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3
O
3
1
a
Refers to isolated yield after chromatography.