Cyclizations intramolecular, aluminum-mediated

The aluminum-mediated Petasis-Ferrier rearrangement is a stepwise [1,3]-sigmatropic process. The first step is the coordination of the Lewis-acid to the 0-atom of the enol. Coordination to the ether O-atom is reversible and nonproductive. Cleavage of the adjacent C-O-bond, assisted by the antiperiplanar lone pair of the etheral O-atom, stereospecifically gives rise to an oxocarbenium enolate species, which cyclizes to the desired oxacycle. The rate difference in the rearrangement for the five- versus six-membered series can be explained by the more facile 6-(enolendo)-endo-trig cyclization. The last step is the intramolecular equatorial hydride delivery. 

Two unselective approaches to the two alkaloids are illustrated in Scheme 50. A straightforward synthesis by King relied on acid-induced intramolecular Mannich reaction of ammoketone 396, prepared from 5-aminopentanal diethyl acetal and pent-3-en-2-one, to give a mixture of ( )-394 (55%) and ( )-395 (20%) (367). The synthesis by Pilli et at. involved a one-pot trimethylsilyl triflate-catalyzed condensation between pent-3-en-2-one and the acyliminium ion derived fium JV-Boc-2-ethoxypiperidine (397) (368,369). Under the reaction conditions, the intermediate 398 underwent spontaneous V-deprotection and cyclization to give a 5.5 1 mixture of ( )-394 and ( )-395 (67%). In the same Scheme is also shown the much shorter stereoselective synthesis of ( )-394 by Beckwith et al, who used a radical-mediated cyclization on the V-acylated 2,3-dihydropyridin-4-one 399 to give the bicyclic product 400 as the sole diastereomer (91%) (370). Compound 400 was readily converted into the target alkaloid by reduction of both carbonyl groups with lithium aluminum hydride followed by reoxidation of the secondary alcohol at C-2. 

---