Nucleophilic desymmetrization, 1,2-diols

Excellent enantioselectivities are observed in the alkylation of various gem-dicarboxylates with both carbon and heteroatom nucleophiles as summarized in Table 8E.2 [71]. Screening various chiral ligands from the DPPBA module revealed that 1,2-diaminocyclohexane derived ligand 5 gives the best results, and the mnemonic of Figure 8E.8 correctly predicts the enantiomer obtained in this reaction. Notably, the corresponding desymmetrization by enzymatic hydrolysis or acylation is not feasible with these 1,1-diol derivatives. 

High enantiomeric excess in organocatalytic desymmetrization of meso-diols using chiral phosphines as nucleophilic catalysts was achieved for the first time by Vedejs et al. (Scheme 13.21) [36a], In this approach selectivity factors up to 5.5 were achieved when the C2-symmetric phospholane 42a was employed (application of chiral phosphines in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). A later study compared the performance of the phos-pholanes 42b-d with that of the phosphabicyclooctanes 43a-c in the desymmetrization of meso-hydrobenzoin (Scheme 13.21) [36b], Improved enantioselectivity was observed for phospholanes 42b-d (86% for 42c) but reactions were usually slow. Currently the bicyclic compound 43a seems to be the best compromise between catalyst accessibility, reactivity, and enantioselectivity - the monobenzoate of hydrobenzoin has been obtained with a yield of 97% and up to 94% ee [36b]. 

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