ChemInform Abstract: Complex‐Induced Proximity Effects: Remote Lithiations of Carboxamides.

Abstract

087ChemInform Abstract The reactions of the unsaturated amide (Ia) (= condition B)) provides the Li intermediate (III) which reacts with various electrophiles such as (IIa)-(IId) or (VIa), (VIb) to give the products (V) and/or (IV), or (VIII), respectively. Formation of only the δ-substitution products (IVb), (IVc) is observed when MgBr2•Et2O is added prior to addition of (IIb), (IIc); on the other hand, the β-substitution product (Vd) is formed exclusively when Et3Al is added. Similar results are obtained from the reactions of (Ib). Lithiation of (Ic) and subsequent treatment with electrophiles (II) or (VIb) gives rise to the products (IX) or (X); the substrates (Id) react in a similar manner. A lithiation at tert. positions can also occur ((XI) → (XIII)). Finally, lithiation of the amide (XIV) is shown to take place at the γ-position (→ (XV)). -The reaction mechanisms are discussed; in the direction of the metalations described, the operation of a complex induced proximity effect that dominates over resonance and inductive effects is suggested.