Esters ortholithiation

Even sulphonate esters 109 are powerful directing groups, competing well with tertiary amides. No substitution accompanies ortholithiation of ethyl or isopropyl benzene-sulphonate by BuLi. Hydrolysis and chlorination of the products 110 gives functionalized sulphonyl chlorides 111 (Scheme 48) °°. 

Even esters can be ortholithiated, provided the electrophile is present in situ during the hthiation. Neopentyl ester 160 gives, on treatment with LDA in the presence of triisopropylborate, the boron derivative 161, which can be deprotected and used in Suzuki coupling reactions (Scheme 79) . Less hindered esters can also be successfully orthohthiated in the presence of a boron electrophile (Scheme 80) . ... 

These reactions have been used in the synthesis of aikaioids such as corydalic acid methyi ester 502 (Scheme i95). Isoiated from Corydalis incisa, 502 is derived from a proposed biosynthetic intermediate in the route to the tetrahydroprotoberberine aikaioids. The 1,2,3,4-tetrasubstituted ring of 502 demands control by an ortholithiation strategy, and the synthetic route proposed by Clark and Jahangir employs a lateral lithiation of 503 and addition to an imine as the key disconnection at the centre of the molecule. 

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