Lateral lithiation enantioselectivity

Enantioselective reactions of laterally lithiated amides and anilides have been reported by Beak and coworkers but these are properly asymmetric transformations in which stereoselectivity arises subsequent to the lateral lithiation step they are not enantioselective lithiations. 

Derdau, V. Snieckus, V. Condensation of laterally lithiated o-methyl and o-ethyl benzamides with imines mediated by (-)-sparteine. Enantioselective synthesis of tetrahydroisoquinolin- 236 1-ones./. Org. Chem. 2001, 66, 1992-1998. 

The 2-ethylanilide 76 may be laterally lithiated with s-BuLi and quenched with Me3SiCl to give the silane 78. The product is formed in 82% ee if the racemic intermediate organolithium 77 is first treated with (-)-sparteine at -25 °C and then Me3SiCl at -78 °C the reaction is an asymmetric substitution, with (-)-sparteine governing the enantioselectivity of the electrophilic quench step. But how does it do this ... 

Another approach to enantiomerically pure planar chiral azaferrocenes involves 2-lithiation of (367) followed by addition of (-)-menthyl-(5 ) — jo-toluenesulfinate. The diastereomeric sulfoxides thus obtained are chromatograph-ically separable, and treatment of each diastereomer with t-BuLi produces an enantiomerically pure planar chiral anion that may be trapped with an electrophile (Scheme 98). Finally, in order to obviate the need for performing a resolution or a chromatographic separation, chiral ligand-mediated enantioselective deprotonations have been investigated. Lithiation of (367) in the presence of (-)-sparteine followed by addition of an electrophile gives the 2-substituted azaferrocene in good enantioselectivities (Scheme 99). However, lateral lithiation of (370) mediated by 5-valine-derived bis(oxazoline) (371) provides planar chiral products with excellent enantios-electivity. 

Lateral Lithiation. An enantioselective synthesis of tetrahydroisoquinolin-l-ones via a BuLi/(—)-sparteine-mediated lateral metalation-imine addition sequence proceeds with highest yields and induction in toluene/ether mixtures (eq 46). ... 

Functionalization of Azaferrocene Catalysts. Chiral azaferrocenes are highly useful in enantioselective acylation as nucleophilic catalysts, and in transition metal-catalyzed asymmetric reactions as chiral ligands. Enantioselective lithiation of an azaferrocene moiety followed by functionalization with (TMS0)2 resulted in a lateral hydroxyl-substituted product with excellent optical purity, but in poor yield (eq 7). The low yield was attributed to the poor reactivity of (TMSO)2 toward the labile azaferrocene substrate. 

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