Dienophiles, chiral

Keywords acrylates, acrylamides, fumarates, a, -unsaturated ketones, vinyl ethers, vinyl sulphoxides, chiral dienophiles, chiral dienes, chiral catalysts polymer-supported chiral Lewis acids... 

Asymmetric Diels-Alder reactions. Unlike methyl crotonate, which is a weak dienophile, chiral (E)-crotonyl oxazolidinones when activated by a dialkylaluminum chloride (1 equiv.) are highly reactive and diastereoselective dienophiles. For this purpose, the unsaturated imides formed from oxazolidinones (Xp) derived from (S)-phenylalanol show consistently higher diastereoselectivity than those derived from (S)-valinol or (IS, 2R)-norephedrine. The effect of the phenyl group is attributed in part at least to an electronic interaction of the aromatic ring. The reactions of the unsaturated imide 1 shown in equation (I) are typical of reactions of unsaturated N-acyloxazolidinones with cyclic and acyclic dienes. All the Diels-Alder reactions show almost complete endo-selectivity and high diastereoselectivity. Oxazolidinones are useful chiral auxiliaries for intramolecular Diels-Alder... 

Stereoselective Diels-Alder reactions have been performed variously, using chirally modified sulfines as dienophiles, chiral ynamines, SMP enamines, SMP acrylamides, and the in situ preparation of SMP A-acylnitroso dienophiles. The [2 + 2] cycloaddition reactions of chiral keteniminium salts obtained from SMP amides with alkenes have been studied. ... 

I.6.I.1.1.1.3. Nonauxiliary-Controlled Dienophiles 1.6.1.1.1.1.3.1. Open-Chain Dienophiles Chiral Enones... 

Asymmetric Diels-Alder reactions using a dienophile containing a chiral auxiliary were developed more than 20 years ago. Although the auxiliary-based Diels-Alder reaction is still important, it has two drawbacks - additional steps are necessary, first to introduce the chiral auxiliary into the starting material, and then to remove it after the reaction. At least an equimolar amount of the chiral auxiliary is, moreover, necessary. After the discovery that Lewis acids catalyze the Diels-Alder reaction, the introduction of chirality into such catalysts has been investigated. The Diels-Alder reaction utilizing a chiral Lewis acid is truly a practical synthetic transformation, not only because the products obtained are synthetically useful, but also because a catalytic amount of the chiral component can, in theory, produce a huge amount of the chiral product. 

To overcome these problems with the first generation Brmsted acid-assisted chiral Lewis acid 7, Yamamoto and coworkers developed in 1996 a second-generation catalyst 8 containing the 3,5-bis-(trifluoromethyl)phenylboronic acid moiety [10b,d] (Scheme 1.15, 1.16, Table 1.4, 1.5). The catalyst was prepared from a chiral triol containing a chiral binaphthol moiety and 3,5-bis-(trifluoromethyl)phenylboronic acid, with removal of water. This is a practical Diels-Alder catalyst, effective in catalyzing the reaction not only of a-substituted a,/ -unsaturated aldehydes, but also of a-unsubstituted a,/ -unsaturated aldehydes. In each reaction, the adducts were formed in high yields and with excellent enantioselectivity. It also promotes the reaction with less reactive dienophiles such as crotonaldehyde. Less reactive dienes such as isoprene and cyclohexadiene can, moreover, also be successfully employed in reactions with bromoacrolein, methacrolein, and acrolein dienophiles. The chiral ligand was readily recovered (>90%). 

Chiral 3-alkenoyl-l,3-oxazolidin-2-ones have been developed and used in highly diastereoselective Diels-Alder reactions by Evans et al. [26] (Scheme 1.34). In this reaction these dienophiles are highly reactive compared with the corresponding... 

The reaction has wide scope in respect of the dienophUe / -substituent. The representative less reactive dienophiles, crotonoyl- and cinnamoyl-oxazolidinone, react with cyclopentadiene at -15 °C and 25 °C for 20 h and 24 h giving cycloadducts in 99% ee and 96% ee, respectively. The 3-chloropropenoyl derivative also affords the adduct in high optical purity (96% ee) this adduct is transformed to 2-(methoxycar-bonyl)norbornadiene, a useful chiral building block. Thus, the 3-chloropropenoyl derivative can be regarded as a synthetic equivalent of an acetylene dienophile. 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

Several highly enantioselective Diels-Alder reactions are known for which the di-enophile does not fit any of the above classes. Corey and coworkers applied the chiral aluminum reagent 36 with a C2-symmetric stilbenediamine moiety (videsu-pra) to the Diels-Alder reaction of maleimides as dienophiles [54] (Scheme 1.68). In most asymmetric Diels-Alder reactions the reactants are usually relatively simple dienes such as cyclopentadiene or monosubstituted butadienes, and unsym-... 

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

The assumed transition state of this reaction is shown in Scheme 5.3. Yb(OTf)3, (J )-(-h)-BINOL, and DBU form a complex with two hydrogen bonds, and the axial chirality of (J )-(-h)-BINOL is transferred via the hydrogen bonds to the amine parts. The additive would interact with the phenolic hydrogen of the imine, which is fixed by bidentate coordination to Yb(III). Because the top face of the imine is shielded by the amine, the dienophiles approach from the bottom face to achieve high levels of selectivity. 

In the presence of 10 mol% chiral Cu(II) catalyst 25, 2-azadienes 26 reacted with dienophiles 27 to afford the corresponding piperidone derivatives in high yields... 

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