Pyrrolidines lithiated formamidines

Similariy low face-selecdvity was found in die addition of lithiated formamidines of tetrahydroquin-oline, dihydroindole and p-carboline to benzaldehyde, although addition of the lithiated 3-car-boline to methyl chloropropyl ketone afforded an 8.5 1 selectivity (Scheme 48). Lithiated formamidines of pyrrolidine and piperidine also add to benzaldehyde in excellent yield, but the diastereoselectivity was not reported. ... 

Proton removal adjacent to a heteroatom is further facilitated if the lithium can be internally coordinated to proximate electron donors, such as the carbonyl oxygen, permitting the formation of dipole-stabilized carbanions. Thus lithiations of various amides, thioamides, imides, esters, Boc derivatives of cyclic amines (pyrrolidines, piperidines, and hexahydroaze-pines), thioesters, )V,iV-dialkylthiocarbamates, and various formamidine derivatives are achieved conveniently using s-BuLi (eqs i3 i7) 32,43b.44.47a,48a Subsequent addition of electrophiles followed by hydrolytic removal of the activating carbonyl, carbamoyl, or formamidine moiety provides a valuable synthetic route to a variety of a-substituted amines, alcohols, and thiols. Successful alkylation of the dipole-stabilized car-banions may require the conversion of the initial lithio carban-ions into their organocuprate derivatives, e.g. by the addition of n-PrC=CCu. ... 

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