Symmetrical dienophiles

Most examples of Diels-Alder reactions reported for both 2-vinyl and 3-vinylindoles involve typical electrophilic dienophiles such as benzoquinone, A"-phenylmaleimide and dimethyl acetylenedicarboxylate (see Table 16.1). T hese symmetrical dienophiles raise no issues of rcgiosclectivity. While there arc fewer examples of use of mono-substituted dienophiles, they appear to react... 

Zamojski A. Chiral (E,E)-l,4-Dialkoxy-l,3-Butadienes. Synthesis, Conformational Studies and Diels-Alder Reactions with Symmetric Dienophiles Chemtracts 2000 13 62-65... 

As the Diels-Alder reactions of 2( lff)-pyrazinones with richly substituted acetylenes can be used to generate diversely substituted pyridines and pyridi-nones, these cyclo additions were investigated under microwave irradiation conditions on the 1,2,3-triazole decorated pyrazinone scaffold. As a proof of concept, the pyrazinones bearing a 1,4-disubstituted-1,2,3-triazole unit, linked via a C-0 bond, were reacted with the symmetrical dienophile dimethyl acetylenedicarboxylate (DMAD), in view of minimizing regioselect-ivity problems (Scheme 28). 

If the reaction of the 2,3-disubstituted-l, 3-butadienes is with a symmetric dienophile, such as maleic anhydride, the 2 and 3 positions in the diene are equivalent, and therefore... 

The generation and Diels Alder reaction of 4,5-bis(bromomethylene)-4,5-dihydrothiazole 39 has been investigated. 39 is a heterocyclic analogue of ortho-quinodimethanes and is generated by treating 4,5-bis(dibromomethyl)thiazole 38 with sodium iodide in dimethylformamide. 39 can be trapped in situ with symmetrical dienophiles to give substituted benzothiazoles such as 40 <98EJOC2047>. 

Chiral (.S, .S )-diazaaluminolidine catalyst brought about the first highly enantioselective catalytic Diels-Alder reaction of an achiral C2v-symmetric dienophile with an achiral diene. Addition of 2-methoxybutadiene to A-o-tolylmaleimide in the presence of 20 mol % (5,5)-diazaaluminolidine gave rise to the cycloadduct in 98% yield and 93% ee one recrystallization from i-PrOH-hexane furnished the enantiomerically pure compound [57] (Eq. 8A.34). The Diels-Alder reaction of 2-((trimethylsilyl)methyl)butadiene and A-aryimaleimide promoted by this catalyst has been successfully applied to the enantioselective total synthesis of Gracilins B and C [58],... 

In spite of the fact that the major product is often predictable, such systems are rarely regiospecific. Because mixtures of regioisomers which must be separated are the rule, either a symmetric diene or a symmetric dienophile is usually employed to avoid such regiochemical issues. 

Diels-Alder reactions.1 This diene (I) undergoes stereospecific Diels-Alder reactions with symmetrical dienophiles (equations 1 and II). The reaction of 1 with... 

Subsequent studies have expanded the scope of this catalyst to include male-imides 5 [49]. In order to obtain enantiomerically enriched cycloadducts with this symmetrical dienophile an unsymmetrical diene was used (Scheme 5) this constitutes the first example of such a process. Ortho substitution on the N-aryl group was found to be crucial to the reaUzation of high enantioselectivity, perhaps to discourage catalyst binding the carbonyl lone pair syn to the M-aryl moiety a transition state analogous to that depicted for the imides (Fig. 15) was invoked. The fact that the dienophile is locked in the s-trans conformer could lend... 

One might expect that a D-A reaction of butadiene with any symmetrical dienophile would have a synchronous TS, since the new bonds that are being formed are identical However, that does not seem to be the case, at least for highly electrophilic dienophiles. For example, highly asynchronous TSs are found for maleic acid and 1,2,4-triazoline, as shown in Figure 10.9. ... 

These heterocycles (Scheme 7) have a plane of symmetry perpendicular to the plane of the molecule therefore, they are expected to form symmetric transition state structures for cycloaddition reactions with symmetric dienophiles such as... 

The heterocycles with heteroatoms in 1, 2, and 4 positions (Scheme 8) have the highest probability to be engaged in Diels-Alder reactions as dienes because two new CC bonds should be formed in the course of the reaction. Due to their symmetry, one can also expect that transition states for reactions with symmetric dienophiles should be symmetric and support synchronous formation of both C-C bonds. The AMI computed transition state structures... 

Symmetrical dienophiles such as dimethyl ethynedicarboxylate and benzyne avoid this regio-chemical problem. Vinylsulfones can serve as ethyne equivalents in this reaction <90JCS(P1)2156>. 

The two successive Diels-Alder additions (tandem cycloadditions) of the C2v-symmetrical tetraene 11 are not regioselective, i.e., mixtures of all the possible regioisomeric bis-adducts are obtained when utilizing non-symmetrical dienophiles. There is no control of the monoadduct on the regio-selectivity of the second cyclo addition. As we have seen with the synthesis of daunomycinone, control of the substitution pattern of the two remote rings A and D of the anthracyclinones can be achieved provided a number of adequate manipulations are carried out with the benzoquinone monoadduct of 11. A more efficient and more versatile way to control the regioselectivity of the tandem cycloadditions is through appropriate and stereoselective double substitutions of tetraene 11. 

Houk s model (Fig. 3 [206,207]) assiunes that the factors that are responsible for the non-planarity of the norbornene double bond intervene in the transition states of the cycloadditions of 5-cis-butadiene moieties grafted at C(2), C(3) of norbornane and 7-oxanorbornane systems. The tighter the transition states, the higher the endo face selectivity. The less synchronous the cycloaddition (e.g., with non-symmetrical dienophiles coordinated to Lewis acids), the lower the endo face preference, steric factors competing in favor of the exo mode of addition. This theory is verified for a large number of cycloadditions including those we reported for deuterated 2,3-dimethylidenebicyclo [2.2.1] heptane [208]. 

The Diels-Alder cycloaddition reaction is a concerted reaction, with no change in the charge density upon going from reactants to the activated complex and finally to the products. Therefore, from the Hughes-Ingold approach, litde solvent effect is expected upon these reactions. In spite of this, dramatic solvent effects are often observed when a non-symmetric dienophile is used, and a mixture of products is formed. For instance, the reaction of methyl acrylate with cyclopentadiene gives a mixture of two products (see Scheme 10.61. 

Diels-Alder Reactions. ( )-I-Trimethylsilyl-1,3-butadiene undergoes Diels-Alder reactions with the usual dienophiles, with unimpaired endo stereoselectivity, but at a somewhat slower rate than 1,3-butadiene itself (eq 1). The regioselectivity with un-symmetrical dienophiles is poor (eq 2). The adducts are allylsilanes, which react with electrophiles in the usual way (eqs 3 and 4) to give cyclohexenes with a double bond shifted from the original position. ... 

Attempts have been made to eliminate the first of these disadvantages by two methods by the use of symmetrical dienophiles not giving structural isomers and by the introduction into the dienes and dienophiles of substituents arranged in a suitable manner that change the structural direction of the reaction (Scheme 18). 

---