Halocyclization, enantioselective

There has also been one report of an enantioselective iodoetherification reaction, which was catalyzed by the Na" " salt of a chiral phosphoric acid organocatalyst (Scheme 13.37) [63]. This transformation was unique in the sense that, in contrast to many other halocyclization reactions, the carbon-Todine bond-forming step was not stereodetermining. Rather, carbon-iodine bond-formation generated meso halonium ions, and it was the ring-opening of these achiral intermediates that was stereodetermining. 

Sakaknra, A., Ukai, A., Ishihara, K. (2007). Enantioselective halocyclization of polyprenoids induced by nucleophilic phosphoramidites. Nature, 445, 900-903. 

Instead, it is more likely that the N-X-bond is cleaved heterolytically, resulting in an equilibrium with the adduct [Nu-X]" (Scheme 12, right Nu=nucleophilic activator). The latter then reacts with the nucleophilic compound to be halogenated. As the N-X bond is likely broken, these reactions are not directly relevant in the specific context introduced above, and only a few illustrative cases will be mentioned (for recent events [122]). One impressive example is the enantioselective halocyclization of polyprenoids which is carried out under addition of 1 equiv. of a chiral nucleophilic phosphoramidite. This nucleophilic phosphoramidite abstracts halenium ions from NIS or NBS via the phosphor atom to form a tight ion pair which then initiates the cyclization reaction by coordination to a double bond in the substrate [123]. 

To achieve high enantioselectivity in the electrophilic halocyclization of simple polyprenoids, Ishihara s group... 

After Hennecke et al. reported chiral sodium phosphate-catalyzed halocyclization via desymmetrization of mci O-haliranium ions formed from l,8-oct-4-ene diols [46a], Denmaric, Huang, and others independently disclosed an enantioselective intramolecular bromocycloetherification reaction with the promotion of the same phosphoric acid, both of which led to exo-cyclized bromofurans 106 as the major products in moderate to good enantioselectivities (Scheme 2.32) [46b,c]. 

Kitagawa O, Hanano T, Tanabe K, Shiro M, Taguchi T. Enantioselective halocyclization reaction using a chiral titanium complex. C/iem. Commun. 1992 (14) 1005-1007. 

A chiral anion phase-transfer system, provided by the l,l -Bi-2-naphthol(BINOL)-derived phosphoric acids (18), has been designed for the enantioselective halocyclization... 

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