Cyclization with Nicolaou reagent

Cyclization of homoallylic alcohols to tetrasubstituted tetrahydrofurans. This cyclization can be effected with almost complete stercocontrol by phenylsclcncnylation with Nicolaou s reagent 1. The products arc reduced with BujSnH/AIBN to trialkylated tetrahydrofurans. 

A variety of specialized reagents have been developed for macrolactonization reactions. Two of the more important are the Corey-Nicolaou reagent, 2,2 -dipyridyl disulfide (232)10 jjjg Mukaiyama reagent, which is 2-chloro-l-methylpyridinium iodide (233). A number of related reagents have been developed, including imidazole disulfide 234 [2,2 -dithio-(4-ferf-butyl-l-isopropylimidazole)]l 2 and imidazole 235 [N-(trimethylsilyl)imidazole].l 3 All of these reagents are effective for the cyclization of co-hydroxy acids, as shown in Table 6.1. For comparison, available cyclization results with DEAD and 234 are included. In this table, a hydroxy acid is converted to a lactone (219). 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

An interesting carbocyclization process was observed when alkenyl stannanes were treated with electrophilic selenenylating reagents containing a non-nucleo-philic counterion. Thus, Nicolaou showed that compound 213 reacted with AT-PSP 11 to form the intermediate 214 which then afforded the cyclopropane derivative 215 (Scheme 32) [109]. Further examples were reported by Herndon [110]. As indicated in Scheme 32, in the presence of tin tetrachloride, the stannane 216 was converted into the cyclopentane derivative 217. This cyclization reaction proved to be quite general with respect to a variety of substitution patterns but it appears to be restricted to the formation of three- and five-membered ring. 

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