Synthesis and Applications of Quinols

The dearomatization of 4-substituted phenols into para-quinols can also be implemented to desymmetrize achiral cyclohexa-2,5-dienone cores, as recently reviewed by Hamed and Canesi [59, 60]. For example, You s group has reported 

51b in aqueous acetonitrile [64]. The resulting pyrrolidine derivative 67 was obtained in 94% yield with an ee of 97% (Fig. 18). Adaptation and further optimization of this phenol dearomatization/thiourea-catalyzed asymmetric aza-Michael reaction sequence also led to the preparation of morpholine derivatives in high yields and enantiomeric excesses [64]. Furthermore, inspired by Rovis earlier work [65], You s group more recently also reported a desymmetrization of para-quinol ethers based on an intramolecular version of the Stetter reaction [66]. This N-heterocyclic carbene-catalyzed umpolimg transform was used to construct tricyclic carbocycles 70 in high yields and enantioselectivities from 45 -type para-quinol ethers 68 using the o-camphor-derived triazolium salt 69 as a chiral catalyst (Fig. 18) [66]. 

Later on, Hamed s group explored another desymmetrization method based on a Pd-catalyzed acetoxylation-cyclization of 45 -type alkyne-tethered cyclohexa-2,5-dienones 75, which were generated by a DIB- or BTI-mediated dearomatization of para-substituted phenols 51 in the presence of propargyl alcohol or but-2-yn-l-ol as solvent (Fig. 20). The control of stereoselectivity of the Pd-catalyzed cycUzatiOTi event was brought by the use of the pinene-derived bipyridine ligand 76, but enantiomeric excesses of only up to 62% could be obtained for the formation of the bicycles 77 [68]. An extension of this exploratory work was later reported by Sasai and co-workers, who used their SPRIX ligand 78 under oxidative conditions to generate a-acetoxylated variants of 77 (i.e., 79) with ee values up to 82% (Fig. 20) [69]. 

various al l grot io Zavtitoustubslituentt, hicliMlng Br at poiMons-2 artd-e 

It is clear that the recent literature on the chemistry of cyclohexa-2,4-dienones of the ortho-apAnol type 46 is much less abundant than that of para-quinols of type 45 (Fig. 16). This can perhaps be mainly attributed to added technical difficulties in 

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