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a 1:1 mixture of diasteroisomers.
Diels-Alder Reaction Facilitated by Physical and Chemical Methods 187
The fluoboric acid-catalyzed aza-Diels-Alder reaction of aldimine and Danishefsky’s diene proceeds smoothly to afford dihydro-4-pyridones in high yields  (Equation 4.16). Unstable aldimines generated from aliphatic aldehydes can be prepared in situ and allowed to react under one-pot reaction conditions. This one-pot Bronsted acid-catalyzed three-component aza-Diels-Alder reaction affords the adducts in good to high yields.
% + ^OSMT HBF4, -40 °C> R^Y°
%r + f MeOH, 0.5 ^ AKN-^ ^
OMe 87-98% (4-16)
Ar = Ph, pMeO-C6H4; R = Ph, PhCH=CH, pX-C6H4 (X = NO2, Me)
Fluoboric acid is also an efficacious promoter of cyclic oxo-carbenium ions (Scheme 4.24) bearing an activated double bond which, in the presence of open-chain and cyclic dienes, rapidly undergo a Diels-Alder reaction . Chiral a,^-unsaturated ketones bearing a'-hydroxy substituents, protected as acetals, react with various dienes in the presence of HBF4, affording Diels-Alder adducts that were isolated as alcohols by hydrolysis of the acetal group by TsOH. Some examples of reactions with isoprene are reported in Table 4.23. The enantios-electivity of the reaction is dependent on the size of the substituent R on the a'-carbon: high levels of asymmetric induction were observed with R = i-Pr (90:1) and R = t-Bu (150:1) and low levels with R = Me (2.7:1) and R = Ph (3.0:1). Scheme 4.24 shows the postulated reaction mechanism.
Gassman  has been a pioneer of ionic Diels-Alder reactions that proceed via in situ generation of cationic species (allylic cations) from olefinic precursors
188 Bransted-Acid-Catalyzed Diels-Alder Reaction
Table 4.23 Diels-Alder reactions via vinyloxocarbenium ions
1. HBF4, DCM
2. TsOH, MeOH
R T (°C) / (h) Yield (%)
Me -78 2 58
/-Pr -45 10 70
/-Bu -20 16 60
Ph 20 16 70
by Bransted acids. Some of these procedures that use protic acids and aminium cation radicals as catalysts are illustrated in Scheme 4.25. A stepwise mechanism has been proposed [92d].
© 0 (pBrC6H4)3NSbCl6 95, 88%
-23 °C, 6min, 88%
An alternative strategy for promoting Diels-Alder reaction by proton involves the activation of dienophile by hydrogen bonding . Biphenylene diol 143 (Scheme 4.26) forms doubly hydrogen-bonded complexes with a,^-unsaturated carbonyl compounds, which strongly accelerate the Diels-Alder
Diels-Alder Reaction Facilitated by Physical and Chemical Methods 189
Ri r2 T(°C) t (h) with 143 without 143
Me H r.t. 0.16 90 3
H H r.t. 0.5 76 10
H Me 55 45 95 21
H Ph 55 73 74 13
Me Me 55 3 83 25
OMe Ph 55 144 13 13
reactions. An ester group of acrylates blocks the formation of hydrogen bonds and consequently no acceleration is observed.
Examples of hydrogen-bonding-promoted Diels-Alder reactions obtained by using alcoholic and phenolic solvents are illustrated in Section 6.2.4.
Nafion-H (144), a perfluorinated resin-sulfonic acid, is an efficient Bransted-acid catalyst which has two advantages: it requires only catalytic amounts since it forms reversible complexes, and it avoids the destruction and separation of the catalyst upon completion of the reaction . Thus in the presence of Nafion-H, 1,4-benzoquinone and isoprene give the Diels-Alder adduct in 80% yield at 25 °C, and 1,3-cyclohexadiene reacts with acrolein at 25 °C affording 88 % of cycloadduct after 40 h, while the uncatalyzed reactions give very low yields after boiling for 1 h or at 100 °C for 3.5 h respectively . Other examples are given in Table 4.24. In the acid-catalyzed reactions that use highly reactive dienes such as isoprene and 2,3-dimethylbutadiene, polymerization of alkenes usually occurs; with Nafion-H, no polymerization was observed.
Recently Nafion-H was successfully used in the Diels-Alder reaction of olefin acetals with isoprene and cyclopentadiene (Scheme 4.27). The reactions work well in DCM at room temperature and Nafion-H did not cleave the acetal group . The recovered Nafion-H was used four or five times without affecting the yield of the cycloadducts.
190 Miscellaneous Diels-Alder Reactions
Table 4.24 Nafion-H catalyzed Diels-Alder reactions in refluxing benzene
t (h) Yield (%)
MA + AN 5 87
BQ + AN 2 92
DMM + AN 15 95