Cascade reactions indolizidine

Nitrogen centered radicals have received considerable attention in recent years. In particular, amidyl radicals have been shown to enter into cascade reactions to form pyrrolizidinone and indolizidinone derivatives. Thus, heating the (9-benzoyl hydro-xamic acid derivative 512 with Bu3SnH in the presence of AIBN produced 513 as a 3 2-mixture of diastereomers (Scheme 88) (99SL441). Separation of compound 513 from the tin residues was difficult, and the isolated yield (17%) was consequently low. When 514 was subjected to identical conditions, a 2 1-mixture of indolizidine 515 and pyrrolizidine 516 was isolated in 42% yield, along with the monocyclic... 

A 1,3-dipolar cycloaddition of the nonstabilized azomethine ylide 6 is the key step in a three-component reaction. The azomethine ylides were generated from (2-azaallyl)stannanes or (2-azaallyl)silanes 5 through an intramolecular iV-alkylation/demetallation cascade. The ylides underwent cycloaddition reactions with dipolarophiles yielding indolizidine derivatives 7-9 <2004JOC1919> (Scheme 1). 

Having established that aminyl radicals can undergo cyclization, several different modes of reaction were explored. Allyl sulfenamide 531 was found to participate in a tandem radical cyclization reaction to produce a 2 2 1-mixture of hexahydro-indolines 532 in 30% yield (Scheme 90) (94T1295). The cyclization failed when a related substrate lacking the allyl group was subjected to the same reaction conditions. Sulfenamide 533 underwent a tandem 5-exo/6-endo-trig cyclization to give indolizidine 534 in 64% yield. Substrates that would require a 6-endo/5-exo cascade to form the indolizidine skeleton (i.e. 535) failed to cyclize under the radical conditions. 

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