Asymmetric hydroxylative phenol dearomatization promoted by chiral binaphthylic and biphenylic iodanes

Angew Chem Int Ed Engl. 2014 Sep 8;53(37):9860-4. doi: 10.1002/anie.201403571. Epub 2014 Jul 22.


The long-standing quest for chiral hypervalent organoiodine compounds (i.e., iodanes) as metal-free reagents for asymmetric synthesis continues. Although remarkable progress has recently been made in organoiodine-catalyzed reactions using a terminal oxidant in stoichiometric amounts, there is still a significant need for "flaskable" chiral iodane reagents. Herein, we describe the synthesis of new iodobinaphthyls and iodobiphenyls, their successful and selective DMDO-mediated oxidation into either λ(3)- or λ(5)-iodanes, and the evaluation of their capacity to promote asymmetric hydroxylative phenol dearomatization (HPD) reactions. Most notably, a C2-symmetrical biphenylic λ(5)-iodane promoted the HPD-induced conversion of the monoterpene thymol into the corresponding ortho-quinol-based [4+2] cyclodimer (i.e., bis(thymol)) with enantiomeric excesses of up to 94%.

Keywords: asymmetric synthesis; dearomatization; hypervalent compounds; iodanes; natural products.