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On the Mechanism of Internal ortho ‐Lithiation in a Mixed Complex Between BuLi and a Chiral Lithium Amide
Author(s) -
Arvidsson Per I.,
Hilmersson Göran,
Davidsson Öjvind
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200211)85:11<3814::aid-hlca3814>3.0.co;2-o
Subject(s) - chemistry , amide , lithium (medication) , lithium amide , reactivity (psychology) , regioselectivity , solvation , selectivity , reaction rate constant , medicinal chemistry , stereochemistry , computational chemistry , organic chemistry , kinetics , molecule , enantioselective synthesis , catalysis , medicine , endocrinology , physics , alternative medicine , pathology , quantum mechanics
The chiral lithium amide Li‐ 1 , prepared from ( S )‐ N ‐[( R )‐2‐methoxy‐1‐phenylethyl]‐ α ‐methylbenzylamine 1 , is known to form a mixed complex with BuLi, i.e. , Li‐ 1 /BuLi. When this complex is kept at room temperature for 3–5 h, a regioselective lithiation of one of the ortho ‐C‐atoms in the amide occurs. Kinetic studies indicate that this reaction proceeds within the mixed aggregate with a first‐order rate constant for the rate‐limiting step k 2 =9.4×10 −4 s −1 (Δ G =21 kcal mol −1 ). Molecular modeling (semi‐empirical PM3) suggests that the observed selectivity and reactivity are a consequence of the solvation and structure of the mixed complex, i.e. , an example of a complex induced proximity effect (CIPE).