Diels-Alder reaction Schmidt reaction

Aube and Golden (dJ) have demonstrated the utility of a combined intramolecular Diels-Alder/intramolecular Schmidt reaction to construct the azepinoindole intermediate 110 (Scheme 5). The Lewis add-catalyzed tandem intramolecular Diels-Alder/Schmidt reaction required azidodiene 109, which was prepared after five steps as a 85 15 mixture of diastereoisomers from diene 108 via a modified Julia olefination between aldehyde... 

Quite recently, a domino Diels-Alder/Prins/pinacol reaction was reported by Barriaulfs group [38]. This novel method is very reliable and efficient for the synthesis of highly functionalized bicyclo[m.n.l]alkanones. In addition, Aube and coworker [39] used a combination of a Diels-Alder and a Schmidt reaction within the total synthesis of the Stemona alkaloid stenine [40]. 

Huisgen et have pointed out that in the Diels-Alder reaction the electronic character of the substituents has practically no influence on the direction of addition. The same point of view has been taken by Fields et cdf and by Schmidt to explain certain apparent anomalies... 

R. R. Schmidt, Hetero-Diels-Alder reactions in highly functionalized natural product synthesis, Acc. Chem. Res. 19 250 (1986). 

The Diels-Alder reaction of benzenoid aromatic hydrocarbons with dienophiles was discovered more than fifty years ago [61, 62]. A classical example is the reaction of anthracene with maleic anhydride (Scheme 5). Although this type of reaction, termed endogenic or endocyclie Diels-Alder reaction, could be expected to be particularly well suited for correlating structure (topology) of benzenoid hydrocarbons with kinetic data, the problem has been systematically studied only very recently. Biermann and Schmidt in a series of publications [12, 29, 45, 63, 64] reported second-order rate constants (k2), measured under standard conditions (1,2,4-trichlorobenzene, 91.5 + 0.2 °C), for the endocyclie Diels-Alder reaction between maleic anhydride and 102 benzenoid hydrocarbons. Each rate constant was measured twice, the values usually... 

Schmidt, R R, Frick, W, Haag-Zeino, B, Apparao, S, De-novo synthesis of carbohydrates and related natural products. Part 28. C-arylglycosides and 3-deoxy-2-glyculosonates via inverse type hetero-Diels-Alder reaction, Tetrahedron Lett., 28, 4045 -4048, 1987. 

Where, as illustrated in the above described example, the Diels-Alder reaction provides avenues into the formation of C-glycosides from furan-derived dienes, the hetero Diels-Alder reaction allows for the direct formation of sugar rings from carbonyl groups. As shown in Scheme 7.5.2, Schmidt, et al.,25 effected reactions between conjugated carbonyl compounds and olefins. The illustrated reaction proceeded in 81% yield giving an adduct which, after further manipulations, was converted to a C-aryl glycoside. 

Diels-Alder reactions of glyoxylates have recently found application in natural product total synthesis. For example, Schmidt and Wagner used such a cycloaddition as a key step in synthesis of uracinine derivative 3, a component of the nucleoside antibiotic blasticidin S (Scheme 4-II).13 Interestingly, when unsymmetrical diene 1 undergoes [4 + 2] cycloaddition with a glyoxylate, only one series of regioisomers is produced, which has the incorrect orientation for synthesis of 3.14 However, if the o-benzoyl... 

Polyoxygenated Natural Products , Aldrichimica Acta, 1986, 1959. R.R.Schmidt, Hetero-Diels-Alder Reaction in Highly Functionalised Natural Product Synthesis, Acc.Chem.Res., 1986, 19, 250. 

Intramolecular variants are the most common type of Diels-Alder reactions employed in total syntheses with carbocycles the most popular targets. Among the broad variety of structures in this class, bicyclic decalin structures, both cis and trans, are readily available on intramolecular Diels-Alder reactions. Aube demonstrated the use of a tandem intramolecular Diels-Alder/Schmidt reaction sequence in his synthesis of three stemona alkaloids. The first steps generates cw-decalin intermediate 124, which undergoes a ring expansion in the Schmidt reaction to furnish tricycle 125. ° ... 

Aube and collaborators reported an expeditious total synthesis of ( )-stenine in only nine steps and 14% overall yield through a cascade intermolecular Diels-Alder reaction/intramolecular Schmidt reaction sequence (Scheme 13.17) [20]. The cascade sequence allowed the construction of the BCD ring system of the natural product in one step, and the routine was also the shortest one among all the completed synthetic strategies so far. 

Scheme 13.17 Total synthesis of ( )-stenine (117) by using cascade intermolecular Diels-Alder reaction/intramolecular Schmidt reaction sequence.

The chemistry of o-benzoquinones, especially their involvement in cycloadditions, has been the subject of extensive investigations in recent years (Nair and Kumar 1994, 1996a, b). In contrast, their aza analogs, viz., o-quinonediimines, have received only scant attention (Friedrichsen and Bottcher 1981), the available information on their cycloadditions being mainly concerned with their participation in Diels-Alder reactions with alkenes (Friedrichsen and Schmidt 1978). 

While catalyst 22/23 has been known to be valuable in other C-C bond-forming strategies, for example, 1,3-dipolar cycloaddition [149], hetero-Diels-Alder reaction [150], Friedel-Crafts-type alkylation [151], double-Michael reaction [152], [2,3]-Wittig rearrangement [153], and Claisen-Schmidt condensation [154], only references are given here. 

Schmidt RK, Mtither K, Miick-Lichtenfeld C, Grimme S, Oestreich M (2012) Silylium ion-catalyzed challenging Diels-Alder reactions the danger of hidden proton catalysis with strong Lewis acids. J Am Chem Soc 134 4421... 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Partially hydrogenated indoles are useful heterocycles. They can easily be obtained by a domino Diels-Alder/Schmidt process, as described by Aube and coworkers [30]. An example is the reaction of the enone 4-90 with a butadiene 4-91 in the presence of the Lewis acid MeAlCl2, which led to tricyclic compounds as 4-93 via 4-92 in over 80% yield (Scheme 4.20). The procedure has also been used for the synthesis of pyrroloisoquinolones, azepinoindolones, and perhydroindoles. 

Also propiogeninic type macrolide moieties should be accessible via this inverse type hetero-Diels-Alder methodology. This was recently exhibited starting from cis-propenylether as heterodienophile (Schmidt, R.R. Haag-Zeino, B. Hoch, M. Liebigs Ann. Chem., in press). In a highly endo-selective cycloaddition reaction and in subsequent diastereoselective transformations of the methyl substituted dihydropyran obtained a 2,4-dimethyl-... 

---