Highly Oxygenated and Reactive Dienes

A major advance in the Diels-Alder chemistry of carbonyl compounds has come with the recognition that simple aldehydes will react readily with many electron-rich oxygenated dienes under Lewis acid cataly- 

The ready availability of optically active NMR lanthanide shift reagents led Danishefsky to investigate the possibility of inducing absolute chirality in these cycloadditions. Using Eu(hfc)3 as catalyst, it was possible to induce modest (20-50%) enantiomeric excesses, depending on the oxygenated diene used and on the reaction conditions. Equation (10) shows one typical result. 

In an exceptionally elegant series of papers, the Danishefsky group has described investigations into the mechanism,stereochemistry, and synthetic applications of this Diels-Alder process. Unfortunately, an in- 

Mechanistically, the cycloaddition reaction is rather complex. Depending on the catalyst or solvent used and the reaction substrates, pericyclic and/or Mukaiyama aldol-like pathways may be involved. The pericyclic mechanism, generally favored by zinc chloride and the lanthanide catalysts, tends to produce adducts having the cis relative stereochemistry at C-5,6. It is assumed that chelation of the aldehyde with the Lewis acid occurs in an anti fashion and that the steric bulk of R is less than that of the Lewis acid-solvent complex L [Eq. (11)], thus favoring a Diels-Alder transition state with R endo. 

Interestingly, when boron triiluoride etherate was used as catalyst, reversal of C-5,6 stereochemistry was observed, affording primarily trana compounds. It was postulated that these reactions involve an aldol-likfl mechanism [Eq. (12)] that is trans (threo) selective. Combinations of thtf pericyclic and aldol mechanisms are probably operative in some cases. 

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The Danishefsky group has examined the uncatalyzed and Lewis adic-catalyzed cycloadditions of highly oxygenated dienes with simple imines in preparation of yohimbine50b analogs and the indolizidine alkaloid ipalbi-dine (Scheme 2-VII).50c What is quite interesting is that some of these dienes are sufficiently reactive that catalysis was not necessary with neutral imines. Also, the reaction seems to show excellent facial stereoselectivity with respect to the imine. 

A series of unconjugated dienes having two double bonds with different reactivity were therefore synthesized. The EPDM rubbers prepared with them on a commercial scale found many important applications especially where oxygen and ozone resistance were needed. However, one drawback limited their growth. Blends of conventional highly unsaturated diene based elastomers and of low unsaturated EPDM rubbers were not readily covulcanizable owing to the large difference in double bond concentration. 

Fumarates. Asymmetric cycloaddition to fumarates has been accomplished by modification of either one or both ends of the diacid. In fact, addition of butadiene to dimenthyl fumarate, reported by Walborsky in 1961, was the first highly selective (89% ds) asymmetric Diels-Alder reaction ever recorded [186,187]. Scheme 6.45 shows examples of cycloadditions of several dienes to dimenthyl fumarate [186-189]. Scheme 6.45a illustrates the presumed reactive conformation of dimenthyl fumarate This conformation features (c/. Figure 6.13a) an trans conformation at C1-C2, cis orientation of the ester ligand relative to the carbonyl oxygen, and orientation of the menthyl moiety to relieve Af3 strain. In this conformation, preferred approach of the diene is from the (rear) C2 Si face. In addition to menthol (Figure 6.12a) 1-mesityl trifluoroethanol (Figure 6.12d) has beep used as a Z w-auxiliary [169]. 

The usual number of publications have appeared within the review year concerning the reactions of singlet oxygen, and Huang et al. have published an order of effectiveness of metal phthalocyanines for the generation of this species. The ethenyl hydrogens of the twisted 1,3-diene (40) have unusually high reactivity towards 02( Ag) (Mori et ai), and Maras et ai have described a convenient route... 

Nafion-H is an efficent catalyst for Diels-Alder reactions (Table 3.39). The reactions of anthracene with maleic anhydride, dimethyl maleate, and dimethyl fuma late were carried out at 333 — 353 K in the presence of Nafion-H catalyst in either chloroform or benzene solvent. It should be noted that the reaction of dienophiles with very reactive dienes such as isoprene and 2,3-dimethylbutadiene can be carried out at room temperature to give the adduct in hi( yields. In usual systems, highly reactive dienophiles undergo polymerization during the desired reactions. In Diels-Alder reactions catalyzed by Friedel-Crafts Lewis acid catalysts, excess amounts of Lewis acid halides are required because of the formation of the complex between the halide and carbonyl oxygen atoms. Here again, Nafion-H catalysts allow easy and clean separation of products and the catalysts are not destroyed upon work up. 

An interesting phenomenon has been observed in the high pressure Diels-Alder reactions of the l-oxa[4.4.4]propella-5,7-diene (117) with 1,4-naphthoquinone, maleic anhydride and N-phenylmaleimide, where the diene 117 undergoes a rearrangement to the diene isomer 118 which, although thermodynamically less favored, exhibits a greater reactivity [40]. The reactivities of the three dienophiles differed since maleic anhydride and N-phenylmaleimide reacted only in the presence of diisopropylethylamine (DIEA) and camphorsulfonic acid (CSA), respectively (Scheme 5.15). The distribution of the adduct pairs shows that the oxygen atom does not exert a consistent oriental dominance on TT-facial selectivity. 

Katsumura, Kitaura and their coworkers [74] found and discussed the high reactivity of vinylic vs allylic hydrogen in the photosensitized reactions of twisted 1,3-dienes in terms of the interaction in the perepoxide structure. Yoshioka and coworkers [75] investigated the effects of solvent polarity on the product distribution in the reaction of singlet oxygen with enolic tautomers of 1,3-diketones and discussed the role of the perepoxide intermediate or the perepoxide-Uke transition state to explain their results. A recent review of the ene reactions of was based on the significant intervention of the perepoxide structure [76], which can be taken as a quasi-intermediate. 

The polyperoxidation of 1,3-dienes is even more dangerous because they are more reactive and some of their polyperoxides are insoluble. With butadiene, the polyperoxidation takes place at temperatures lower than -113 C the oxygen is absorbed very quickly and forms insoluble polyperoxides that precipitate. It was estimated that at a temperature of 25°C the critical mass of such a compound consists of a sphere of diameter 9 cm. This diameter decreases quickly with the temperature. Isoprene behaves in the same way, but its polyperoxide is soluble, in these conditions, the monomer can absorb any temperature rise which would be caused by the beginning of a decomposition, thus reducing risks. If the monomer evaporates, a gum that detonates at 20°C is formed if the medium is stirred. With cyclopentadiene, polyperoxide is more stable and only detonates at a high temperature. 

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