Absolute and relative facial selectivities in organocatalytic asymmetric chlorocyclization reactions.

Though (DHQD)PHAL-catalyzed chlorocyclizations of 1,1-disubstituted olefins show useful (and in some cases, reversible) asymmetric induction, stereochemically complete descriptions of these alkene additions have remained largely unknown. Herein, based on a combination of NMR, derivative, isotope labeling, and computational studies, we present detailed stereochemical analyses of chlorocyclizations of nucleophile-tethered 1,1-disubstituted styryl systems. The selectivities of the two asymmetric bond-forming processes, namely electrophilic chlorine attack and nucleophilic ring closure, are thus mapped out independently. Under the established optimal conditions, four related chlorocyclizations were subjected to this analysis. All showed a strong preference for Cl delivery from the same face of the alkene. However, depending on reaction conditions and substrate identity (carboxylic acid, amide or carbamate), the internal nucleophiles may close with a strong net preference for either or addition relative to the Cl atom. Studies of both uncatalyzed and (DHQD)PHAL-catalyzed processes place new boundary conditions on the role of the catalyst in these reactions.