Highly enantioselective protonation of the 3,4-dihydro-2-methylnaphthalen-1(2H)-one Li-enolate by TADDOLs

A series of nine TADDOLs (=a,a,a′,a′-tetraaryl-1.3-dioxolane-4,5-dimethanols) la - li, have been tested as proton sources for the enantioselective protonation of the Li-enolate of 2-methyl-1-tetralone (= 3.4-dihydro-2-methylnaphthalen-1(2H)-one). The enolate was generated directly from the ketone (with LiN(i-Pr)₂ (LDA)/MeLi) or from the enol acetate (with 2 MeLi) or from the silyl enol ether (with MeLi) in CH₂Cl₂ or Et₂O as the solvent (Scheme). The Li-enolate (associated with LiBr/LDA, or LiBr alone) was combined with 1.5-3.0 equiv. of the TADDOL at -78° by addition of the latter or by inverse addition. 2-Methyl-1-tetralone of (S)configuration is formed (≤80% yield) with up to 99.5% selectivity if and only if (R,R)-TADDOLs (1d, e.g) with naphthalen-1-yl groups on the diarylmethanol unit are employed (Table). The reactions were carried out on the 0.1- to 1.0-mM scale. The selectivity is subject to non-linear effects (NLE) when an enantiomerically enriched TADDOL 1d is used (Fig. 1). The performance of TADDOLs bearing naphthalen-1-yl groups is discussed in terms of their peculiar structures (Fig. 2).