Diels-Alder fragmentation approach

For a tandem Diels-Alder/fragmentation approach to the eleutherobin aglycone, Winkler et al. used Marshall s protocol in an early step of the synthesis. The building block 95 was prepared in that way (Scheme 15.24) [56]. 

An ingenious new approach to the synthesis of pseudotabersonine (707) has been developed by Carroll and Grieco (391). Here the intermediate oxindole 708 was constructed by a remarkable process in which the anion from the precursor oxindole 709 was alkylated by Grieco s spiroaziridinium triflate 710. A-Benzylation of the product 711, followed by a reverse Diels-Alder fragmentation, then an intramolecular aza-Diels-Alder cyclization, gave the tetracyclic oxindole 708. Introduction of the three-carbon unit into position 2 in 70iB was achieved by condensation with 2-lithio-l,l-diethoxy-2-... 

Another approach for the construction of rings is to use reactions which start with two acyclic compounds and produce cyclic products. There are many of these processes, but the most used and most useful is the Diels-Alder reaction. This is a reaction between a diene and an olefin to give a new six-membered ring. It is also termed a 4 + 2 cycloaddition because one partner (the diene) containing four 7r electrons adds to a two-electron fragment (the olefin) containing two it electrons to yield a ring. 

Unsubstituted polyacetylene, like many other conductive polymers, is an intractable material and thus its processing into useful shapes and morphologies is limited. One solution to the processing problems has been the use of soluble precursor polymers that can be transformed into conductive polymers. Application of ROMP in the formation of soluble polyacetylene precursors was elegantly pioneered by Feast and coworkers [61]. Using this approach, a precursor polymer is synthesized by the ROMP of a cyclobutene derivative. Once synthesized, the precursor polymer can undergo a thermally promoted, retro-Diels Alder reaction to split off an aromatic fragment and produce polyacetylene, Eq. (42). 

After having developed a reliable route to the enantiopure carboxylic acid 4a, we next turned our attention to gain access to the enantiopure decalin fragment. One of the most efficient approaches to this structural motif is the intramolecular Diels-Alder reaction. The first systematic studies in the racemic series were performed by Roush and co-workers in 1981 (Roush and Hall 1981). Evans (Evans et al. 1984, 1988) and Oppolzer (Oppolzer and Dupuis 1985) showed that chiral auxiliaries in combination with strong Lewis acids allowed the generation of the endo adducts with excellent diastereoselectivities (Scheme 5). Recently, chiral Lewis acid catalysts were successfully used by Evans (Evans et al. 1999) and Corey (Zhou et al. 2003). 

Biemann (1962a) noted that his type-D reaction was the mass-spectrometric equivalent of the reverse Diels-Alder reaction. Several examples of this type of fragmentation are now known (Budzikiewicz et al., 1965 Maccoll, 1968a). Dougherty (1968b), assumed that both the thermal and electron impact-induced processes were electrocyclic in his explanation of the apparent similarity between the type D process and the reverse Diels-Alder reaction in terms of a simple perturbation molecular orbital approach (Section VIIID). 

An alternative mechanism for the Diels-Alder reaction involves a stepwise pathway (Reaction 4.3). Here, one end of the butadiene and ethylene fragments approach each other, passing through transition state 6, to form a diradical intermediate 7. In a second distinct chemical step, the second new o-bond is formed through transition state 8 to give cyclohexene. 

The first phase of the total synthesis of thiostrepton 303, a highly complex thiopeptide antibiotic, has been described. Retrosynthetic analysis of thiostrepton revealed units 304-308 as potential key building blocks. Concise and stereoselective constructions of all these intermediates have been achieved. The synthesis of the dehydropiperidine core 308 was based on a biosynthetically inspired aza-Diels-Alder dimerization of an appropriate azadiene system, an approach that was initially plagued with several problems which were, however, resolved satisfactorily by systematic investigations. The quinaldic acid fragment 305 and the thiazoline-thiazole segment 306 were synthesized by a series of reactions that included asymmetric and other stereoselective processes (Scheme 113) <2005JA11159>. 

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