Anionic intramolecular Diels-Alder cyclization

A separate study of the alkylations of 1 has been reported by Oppolzer and co-workers. The group has employed LDA, LiTMP, and n-C4Hs,Li to metalate 1. The resulting anion condenses with a variety of electrophiles (primary alkyl bromides, iodides, tosylates, disulfides, and acyl derivatives) to afford the corresponding monosubstituted derivatives in 30-95% yield. If the alkyl group contains a double bond in the 4- or 5-position, polycyclic compounds are prepared by thermal extrusion of SO2 followed by intramolecular Diels-Alder cyclization. 

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-... 

The first approach in the synthesis of the tricyclic system was published by Mark6, who used an anionic cyclization strategy. Unfortunately, the final intramolecular Diels-Alder reaction only proceeded in poor yield and gave a mixture of adducts in a 1 1 ratio, see Scheme 17 [78]. 

This section is devoted to cyclizations and cycloadditions of ion-radicals. It is common knowledge that cyclization is an intramolecular reaction in which one new bond is generated. Cycloaddition consists of the generation of two new bonds and can proceed either intra- or intermolecularly. For instance, the transformation of 1,5-hexadiene cation-radical into 1,4-cyclohexadienyl cation-radical (Guo et al. 1988) is a cyclization reaction, whereas Diels-Alder reaction is a cycloaddition reaction. In line with the consideration within this book, ring closure reactions are divided according to their cation- or anion-radical mechanisms. 

One very fascinating domino reaction is the fivefold anionic/pericyclic sequence developed by Heathcock and coworkers for the total synthesis of alkaloids ofthe Daphniphyllum family [351], of which one example was presented in the Introduction. Another example is the synthesis of secodaphniphylline (2-692) [352]. As depicted in Scheme 2.154, a twofold condensation of methylamine with the dialdehyde 2-686 led to the formation of the dihydropyridinium ion 2-687 which underwent an intramolecular hetero-Diels-Alder reaction to give the unsaturated iminium ion 2-688. This cyclized, providing carbocation 2-689. Subsequent 1,5-hydride shift afforded the iminium ion 2-690 which, upon aqueous work-up, is hydrolyzed to give the final product 2-691 in a remarkable yield of about 75 %. In a similar way, dihydrosqualene dialdehyde was transformed into the corresponding polycyclic compound [353]. 

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