Alder-ene-type reactions

Reactions of the allylic position of alkenes with carbonyl or imine electrophiles are known as Prins reactions and have been discussed in previous sections (3.2.9). More examples of similar Alder-ene-type reactions (the Prins reaction) will be discussed in Chapter 8. 

Trost, B.M., Probst, G.D. and Schoop, A. (1998) Ruthenium-catalyzed Alder ene type reactions. A formal synthesis of alternaric acid. Journal of the American Chemical Society, 120, 9228-9236. 

In a similar manner to normal Alder ene type reactions, transition metals also catalyze the ene reactions of dienes with olefins36 -38,50. This type of reaction can be considered as a 1,4-addition of an alkene to a diene. Diastereoselective asymmetric induction can be achieved if the alkene unit is incorportated into a chiral acetal37. 

Catalyst 2 can also be used in a butenolide synthesis on the basis of a ruthenium catalyzed Alder ene type reaction. [6-9] In the course of a reaction sequence directed to the synthesis of acetogenins, Trost et al. coupled alkene 16 with propargyl alcohol 17 in the presence of 2 to give butentolide 18 in up to 82 % yield (Scheme 6). 

Diels-Alder condensations of fumaric and maleic acid polyesters with various dienes can serve as another example. These reactions require 20 hours at room temperature. Diels-Alder condensations can also be carried out on polymers of 1,3,5-hexatriene, 1,3,5-heptatriene, and 2,4,6-octatriene. Sulfonate-substituted maleic anhydride adds to low-functionality hydrocarbon elastomers, like EPDM, presumably via an Alder-ene-type reaction ... 

Catalytic intermolecular coupling of alkene and alkyne is quite a challenging task. Nevertheless, cyclopentadienyl rutheniumcomplexes are able to catalyze alkyne-alkene coupling (an Alder-ene type reaction) to a mixture of the re-gioisomeric products 120 and 121 (Scheme 52). The most efficient catalysts are the complexes 78 or 53. The latter is more reactive. The scope of the reaction with respect to substituents attached to the both reactants is enormous ester, hydroxy, nitrile, ether, amino, and arylhalide groups are tolerated. Both terminal and internal alkynes and alkenes can be used. Some typical examples are summarized in Table 24 [67,69]. 

Alder-ene cyclizations involve enyne substrates with an aUylic hydrogen at the olefinic termini. The pioneering work of Trost initially demonstrated that palladium acetate efficiently promote intramolecular Alder-ene type reactions of 1,6- and 1,7-enynes, leading to 5- or 6-membered rings with exocyclic methylene bonds (Fig. 10.2) [16]. These processes generate a tetrahedral stereogenic centre from a planar sp -carbon in the starting material. Therefore, asymmetric variants... 

Hetero-Diels-Alder reactions performed with trifluoromethyl-substituled heterodienes or with trifluoromcthyl-substituted heterodienophiles have resulted in the synthesis of a large number of fluoro-heterocyclic compounds. Ketones, thioketones, imincs, nitriles, and their parent a,/3-unsaturated systems have been studied in cycloaddition reactions. Cycloadditions are regioselec-tive. An interesting aspect is the competition with ene-type reactions, aldol reactions and, depending on the partners, with [2 + 2]-cycloaddition reactions. 

In some palladium-catalyzed cyclizations of enynes a [2 + 2] cycloaddition with subsequent metathesis-like rearrangement leads to other cyclic products50,51. The transition metal catalyzed Alder ene type cyclization reactions can also be applied to diynes52 and to enal-lenes53-55. The latter reaction is best performed using a polystyrene-supported nickel(II)/ chromium(II) catalyst. With the appropriate choice of substituents complete stereoselectivity can be achieved using this method55. 

MO calculations have been carried out for the [4-f2] Diels-Alder-like cyclization of aminoboranes R2B = NR 2 with substituted m-1,3-butadienes <2003OM3748>, and for the [4-1-2] ene-type reactions between iminoboranes... 

An inverse electron demand Alder-Ene reaction has been reported in which a nitrilium ion acts as the ene and an arene as enophile. The reaction occurred at room temperature and was proposed to be a double Alder-Ene reaction. The first step provided compound 133, which could undergo a stepwise addition of the vinyl sulphide to the azonia-allene followed by elimination or alternatively, a second concerted Alder-Ene type mechanism was suggested. The heterobicycle 134 was isolated in 90% yield. 

A catalyst system consisting of Pd2(dba)3 and AcOH or PhC02H effectively promotes the Alder-ene-type cycloisomerization of 1,6-enyne 34 to give 1,4-diene 35 (phosphine ligand is sometimes necessary). A cationic Pd(II) hydride species is believed to be generated in these reactions, the anion of which affects catalyst activity and selectivity (eq 22). 

Catalyst Cl promoted Alder-ene type cyclizations of 1,6-enynes with sterically congested, trisubstituted double bonds and either ether or amide functions in the tethering chain (Fig. 10.27). These reactions afforded the expected dihydrofuranes and pyrrolines with high levels of enantioselectivity. Minor amounts of the isomerized endo-olefin product B were occasionally isolated. 

From this short overview it appears that the majority of the recent studies on enantioselective cycloisomerizations have been focused so far on asymmetric Alder-ene type cyclizations with Pd and Rh catalysts, since these reactions represent an economical access into synthetically usefiil cyclopentene and cyclohexene frameworks (Sects. 10.2.1 and 10.3.1). For these processes, efficient chiral catalysts have been afforded mainly by atropisomeric diphosphines, but also DuPHOS, Skewphos and phosphine-oxazolines can occasionally represent suitable auxiliaries. 

Recent study of silenes has clearly established their ability to act as dienophiles in [2 + 4] Diels-Alder-type reactions involving 1,3-dienes. However, it has also been clearly demonstrated that products of the ene reaction commonly accompany the [2 + 4] cycloadducts and may on occasion be the major products. In addition, unlike those in carbon chemistry, [2 + 2] cycloadditions are often observed to occur in competition with the above processes—not only from reactions of silenes with dienes... 

The chemistry and utility of zinc-based Lewis acids are similar to those of their magnesium analogs. Their mild Lewis acidity promotes several synthetic reactions, such as Diels-Alder reactions, hetero Diels-Alder reactions,229 radical-mediated reactions,230 ene-type cyclization, and Simmons-Smith reactions. 

Trost et al 2 briefly explored using non-enone enophiles. Simple alkenes led to the formation of complex mixtures of isomers due to the presence of an additional set of /3-hydrogens. Many other types of substrates were incompatible with reaction conditions. Vinyl ketones were, therefore, the only coupling partners shown to be effective in the ruthenium-catalyzed Alder-ene couplings of allenes and alkenes. 

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