Desymmetrization tether

SCHEME 11 Enantioselective desymmetrization of malonate-tethered cyclohexadienones. 

One of our simplest attempts at overriding the inherent diastereoselectivity was inspired by our success with using Cinchona alkaloid-based phase-transfer catalysts to promote the enantioselective desymmetrization of achiral malonate-tethered cyclohexadienones (Scheme 27). When catalyst B was... 

Lautens reported a new enantioselective Rh-catalyzed domino reaction that gives access to fused heterocycles 122 by desymmetrization of alkyne-tethered cyclohexa-dienones 120 [40]. The syn addition of the Rh-aryl species 124 onto the alkyne led to two new C-C bonds and two stereocenters with good enantioselectivity (Scheme 11.25). 

A new enantioselective Rh-catalyzed domino transformation of boronic acids with a cyclohexadienone-tethered alkyne gave access to fused heterocycles by desymmetrization of alkyne-tethered cyclohexadienones via the formation of two new C-C bonds and two new stereocenters with good enantioselectivities, syn-addition of the rhodium-aryl species onto the alkyne (130L1148). 

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]. 

In 2005, Hanson et al. utilized this concept with a phosphate tether in the desymmetrization of C2-symmetric (3S,5S)-l,6-diene-diol (S,S)-24 (Scheme 4.9)... 

The synthesis of bicyclic phosphate triester 26 has been accompUshed via a desymmetrization of C2-symmetric diol 24 using a phosphate-tether mediated... 

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