Nucleophilic substitutions tetrahydropyrans, cyclization

Aubele et al. studied the aqueous Prins cyclization using cyclic unsaturated acetals as oxocarbenium ion progenitors and allylsilanes are used as nucleophiles. Cyclizations proceed efficiently inside Lewis acidic micelles (of cerium salt) in water. A variety of vinyl- and aryl-substituted tetrahydropyrans with excellent stereocontrol was obtained (Eq. 3.26).113... 

Nucleophilic substitution of cz.s-2,3-disulfonates of ribofuranosides normally occurs at position 3. For example, treatment of ditosylate 18 with NaNs in DMF, followed by removal of the tetrahydropyran group afforded 3-azidofu-ranoside 19. Reductive cyclization by lithium aluminum hydride gave " epimine... 

In the presence of a homoaUylic alcohol and a nucleophile, for instance, the epoxide rearrangement will be followed by a Prins cyclization to provide substituted tetrahydropyrans (172) [50]. 

Oxygen nucleophiles Intramolecular oxa-Michael cyclization of a,/ -unsaturated carbonyl compounds (278) (e.g. thioesters, oxazolidinone imides, and pyrrole amides), catalysed by Brpnsted acids, such as camphorsulfonic acid (CSA), has been reported to afford 2,6-cis-substituted tetrahydropyrans (279) with good to excellent stereoselectivity (7 1 to >20 1 dr). The approach has been claimed to be superior to that mediated by bases and is complementary to the ruthenium-catalysed cyclization affording anal- 0 ogous products (149) discussed earlier. 

A further variation of these functionalizations of cyanoarenes is the NOCAS process [14, 15]. As shown in Scheme 14.2, path g, this involves the addition of a nucleophile (which is often the solvent) to the donor radical cation. The thus-formed neutral radical adds to the acceptor radical anion, while rearomatization by the loss of an anion leads again to an overall ipso-substitution. AUenes could be used as the donors in these reactions, as shown recently by Arnold [50]. Accordingly, the irradiation of TCB in the presence of tetramethylaUene (15) in a 3 1 MeCN/MeOH mixture afforded 1 1 1 arene-allene-methanol adduct 16 in 48% yield (Scheme 14.9, central part). Interestingly, the addition of methanol took place exclusively at the central allene carbon, while aromatic substitution occurred through the terminal carbons. co-Alkenols, in which an O-nucleophile and an easily oxidized moiety are both present, could also be used. In the latter case, the initial ET was followed by a cyclization, yielding aryl-substituted tetra-hydrofurans or tetrahydropyrans as the final products via a tandem Ar—C, C—O bond formation [51]. 

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