Addition homoconjugate, intramolecular

In addition to the aforementioned types of intermolecular homoconjugates, there are also intramolecular homoconjugates, examples of which we have already mentioned with regard to the titrations of (a) ethylenediamine with acid (p. 248) and (b) of salicylic acid with base (p. 245). This phenomenon of intramolecular hydrogen bonding is usually called chelation, and so the conjugates concerned are preferably designated chelates. 

Danishefsky and co-workers have used activated cyclopropanes to promote intramolecular alkylation of an amino function, followed by lactam formation to provide a new entry to the pyrrolizidine ring system.20 This route is outlined in Scheme 1. Cyclopropanation of the phthalimido-olefin (19) was achieved with dimethyldiazomalonate in the presence of copper bronze. Treatment of the cyclopropane derivative (20) with hydrazine released the amine, which gave the lactam ester (21) in quantitative yield. This corresponds to intramolecular homoconjugate addition entirely in the spiro mode.21 It seems reasonable that the first step in this process is internal alkylation of the amine by the activated cyclopropane. The alternative... 

Another mechanistic possibility that has been proposed with Mgl2- and Lil-promoted annulations of (3-ketoester cyclopropanes 22 involves the bis-coordination of the p-ketoester group to magnesium followed by homoconjugate addition of iodide ion to the VCP, forming an allyl iodide intermediate 23. The (E)-isomer of this intermediate can only revert back to the VCP via an 5 2 pathway, whereas the (Z)-isomer would undergo intramolecular 5 2... 

These intramolecular homoconjugate additions provide a simple entry into fura-noid systems. The p-keto-ester (461) cyclizes in a spiro mode to (462a), whereas with dimsylsodium the isomer (462b) is formed. Similarly, the keto-ester (463 R = COjMe) is cyclized to (464) by sodium hydride, but the ketone (463 R = H) affords only the Dieckmann product (465) under these conditions. ... 

Pyrrolizidines and indolizidines are also available by this type of reaction, from the amines liberated by the action of hydrazine on the phthalimides (466 n = 3 or 4). No intramolecular homoconjugate addition was observed for the lower homologue (466 n = 2), however, the lactam (467) being the only product. ... 

A number of necine bases have been synthesised by intramolecular opening of activated cyclopropanes by Danishefsky etal. (95). Initially, ( )-isoretronecanol (26) was prepared as outlined in Scheme 8. Intramolecular homoconjugate addition of the amine (31) took place with complete inversion of stereochemistry to give the pyrrolizidinone (32). Removal of the hydrazide group from (32) and reduction of the product (33) yielded ( )-isoretronecanol (26). Analogous treatment of a stereoisomer of (31) afforded ( )-trachelanthamidine (9) (95). 

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