Oxazolines lateral lithiation

Oxazolines , imidazolines and tetrazoles can all be laterally lithiated. Oxazolines have been used in this regard rather less than for ortholithiation (Scheme 200). 

Lateral lithiation of (d )-4-isopropyl-2-(o-tolyl)oxazoline and reaction with aldehydes provides the addition products 1148 with moderate to good diastereoselectivity. The addition of TMEDA is vital for any diastereoselectivity to be observed. The major (,S,A)-products lactonize faster under acidic conditions providing dihydroisocoumarins 1149 in up to ee 97% (Scheme 286, Table 53) <2005T3289>. Similarly, the addition of laterally metallated o-toluates to chiral aldehydes provides a key dihydroisocoumarin during a total synthesis of AI-77-B <1999J(P1)1083>. 

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. 

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