C O M M U N I C A T I O N S
Table 2. Diels-Alder Reaction of Representative â-alkyl and â-aryl
time and with excellent yield and diastereoselectivity. Once again,
although the reaction with cyclopentadiene to give 15 proceeded
without the need for any catalyst, it gave a low endo:exo selectivity
ratio, which could be improved when TfOH was used. The â-aryl-
substituted enones 7-10, in turn, also proved to be good substrates
for the present Diels-Alder reaction, regardless of the electron-
neutral, electron-rich, or electron-poor nature of the aryl substituent.
The stereochemical assignment for the adducts was made by optical
rotation measurements of the products obtained after detachment
of the auxiliary, and by X-ray analyses.11
Enones with Dienes Catalyzed by TfOHa
In conclusion, we have documented a highly diastereoselective
strategy for metal-free, Brønsted acid-activated Diels-Alder reac-
tions and have set up the minimum structural requirements of the
substrate dienophile.
Acknowledgment. We thank The University of the Basque
Country and Ministerio de Ciencia y Tecnologia (Spain) for
financial support. A grant to A. Lecumberri from UPNA is
acknowledged.
Supporting Information Available: Complete experimental pro-
cedures, determination of stereoisomeric mixtures, and spectroscopic
data (PDF); crystallographic data (CIF). This material is available free
References
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a Reactions conducted on a 1 mmol scale in CH2Cl2 at -78 °C; ratio
diene:enone:TfOH 5:1:0.1, unless otherwise stated. b Determined by HPLC
or by 13C NMR. c Diastereomeric ratio of the endo or major regioisomer
(as applicable) determined by 13C NMR. d Reaction conducted in the absence
of catalyst. e Yield not determined. f Reaction performed with 30% of TfOH.
g A byproduct is formed when a longer reaction time was applied. Not
characterized.
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Riant, O.; Kagan, H. B. Tetrahedron Lett. 1989, 30, 7403-7406. (b) Kelly,
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temperature). Enone 3 reacted in a similar manner when cyclic
dienes were employed. Even in the absence of any promoter, the
highly reactive cyclopentadiene reacted with 3 to give 12c with a
16:1 ratio of isomers. Notably, when the reaction was carried out
with either TFA (30 mol %) or TfOH (10 mol %) catalysis, the
endo:exo ratio of the produced isomers improved to 49:1. On the
other hand, the reaction with cyclohexadiene once again required
the presence of either TFA (30 mol %) or TfOH (10 mol %), which
lead to 12d, essentially as the only isomer.
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(8) Pulz, R. Synlett 2000, 1697.
On the basis of these results, which demonstrate the crucial effect
that the Brønsted acid has, not only on the reactivity but also on
the stereoselectivity,10 TfOH was selected as the optimal catalyst
for further experiments. To this end, enones 6-10 were prepared
easily from 2 and 3,11 and their reactions with representative dienes
were examined (Table 2). In the presence of TfOH (10 mol %),
enone 6 reacted with both acyclic and cyclic dienes 11a-d at -78
°C in CH2Cl2 to give the respective cycloadducts within a short
(9) CH3CO2H, BrCH2CO2H, Br2CHCO2H, Cl2CHCO2H, HCO2H led to
inferior results compared to those with TFA in terms of reaction efficiency
and stereoselectivity.
(10) While essentially the same effect was observed when toluene was
employed, the unchanged starting materials were recovered when Et2O
or THF were the solvents used. The ability of ethereal solvents to interfere
during the hydrogen-bonding activation process might account for the
differential behavior.
(11) See Supporting Information for details.
JA025906E
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