SN2 cyclization

After epoxidation of the terminal olefin in syn-89 the pyrrolidine 91 was formed by reductive cleavage of the Cbz-protection and concomitant Sn2 cyclization of the free amine to epoxide 90. In five additional steps (+)-preus-sin (2) was synthesized with an overall yield of 19%. After AT-methoxycar-bonylation and oxidation of the alcohol to an aldehyde the alkyl side chain was introduced by a Wittig reaction. 

Scheme 15 Mimics of natural cyclopeptide alkaloids by Ugi CR + Sn2 cyclization...

Trost s synthesis138 of desethylibogamine (233) illustrates the application of a new approach to alkaloid synthesis, in which the two vital cyclization processes involve catalysis by palladium complexes protection of the nitrogen by formation of an amide, so often necessary in conventional syntheses, is here unnecessary. The first of the cyclization processes, (234)—>(235), results in a very neat formation of the isoquinuclidine ring system via a palladium-catalysed SN2 cyclization of the tryptamine derivative (234) (Scheme 24). 

The total synthesis of the natural furano-fused dihydroisocoumarin (+)-monocerin was accomplished in 15 steps with a 15.5% overall yield starting from but-3-en-l-ol via tandem dihydroxylation-SN2 cyclization and a copper-catalyzed tandem cyanation-lactonization process (140BC5973). The formation of the 3,4-dihydroisocoumarin ring in the total synthesis of natural (+)- and unnatural (-)-scorzocreticin involves a palladium-catalyzed intramolecular carbonylation and lactonization of l-aryl-2-(2-iodoaryl) ethan-l-ol (14T8161). 

Non-racemic epoxide 307, prepared from (+)-epichlorohydrin, was alkeny-lated to give allyl silane 308, which was converted into allyl stannane 309. Corey s chiral boron reagent-mediated asymmetric allylation [120] to aldehyde 311 provided homoallylic alcohol 306 with a 11 1 diastereomer ratio. Intramolecular Sn2 cyclization of the corresponding 7-hydroxy-3-TsO unit derived from 306, followed by hydrolysis of the dithiane, afforded aldehyde 312 (Scheme 66). 

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