Hetero Diels-Alder reaction ring contraction

The array of dienophiles amenable to these hetero Diels-Alder reactions is not limited to enol ethers and enamines since allylsilanes and simple alkenes have also been successfully employed [370, 371]. More recently, it has been shown that methoxy allenes such as 4-41 undergo formation of 6H-l,2-oxazines 4-43 upon cycloaddition to nitrosoalkenes such as 4-34 and subsequent tauto-merisation of the intermediate exo-methylene compound 4-42 (Fig. 4-9) [372, 373]. In these studies, 4-43 proved to be a versatile synthetical intermediate allowing oxidative demethylation or reductive removal of the methoxy group as well as nucleophilic substitutions after the generation of an azapyrylium ion [372 - 374]. Furthermore, ring contraction reactions of these oxazines leading to pyrroles [373] and y-lactames [375] are known. 

Cyclic nitrones generated by [4+ 2]-cycloaddition of nitroalkenes undergo various, synthetically very valuable reactions. Thus, Denmark et al. have developed an elegant access to different enantiopure, 3- and 3,4-substituted pyrrolidine derivatives by reductive ring contraction of the cyclic nitrone resulting from a hetero Diels-Alder reaction [389,390]. Upon reaction of -2-nitrostyrene 4-51 with the chiral enol ether 4-52 in the presence of the bulky Lewis acid MAPh (4-53), three diastereomeric cycloadducts 4-54, 4-55 and 4-56 were formed. Hydrogenolysis of the main product 4-54 yielded the desired pyrrolidine 4-57 in excellent optical purity and allowed nearly quantitative recovery of the chiral auxiliary (Fig. 4-12) [391]. It is noteworthy that the nature of the Lewis acid catalyst, especially its steric demand, decisively influences the stereochemical course of such cycloadditions [392]. 

Taken as a whole, the proposed synthetic route amounts to a retro-synthetic blueprint of extraordinary symmetry and appeal with two different hetero-Diels—Alder reactions comprising the essence of the strategy. Without question, achieving this total synthesis would be predicated on successful execution of each step in a tandem manner, a matter of some consequence as none of the proposed transformations had ever been demonstrated in non-monomeric contexts. For instance, the numerous intermediates of the assumed mechanism for the Komfeld reductive ring contraction conversion (vide infra) could provide ample opportunity for undesired side reactions in the projected isochrysohermidin synthesis. Thus, con-... 

Several groups of workers have been occupied with the synthesis of spiro-ketals and polyoxa-polyspiro-alkanes. The hetero Diels-Alder reaction between furanoid or pyranoid exocyclic vinyl ethers and acrolein established the spiro-ketal systems (76) and (77). Oxidative ring-contraction led to 1,6-dioxaspiro-alkane carboxylic acids (Scheme 9), which are useful subunits for polyether antibiotic synthesis. Phillips and his co-workers have tackled the problem using... 

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