Carbon-nitrogen bonds intermolecular amidation

Intramolecular carbon-nitrogen bond formation is possible utilizing a catalytic system derived from Pd2(dba)3/P(2-tolyl)3, which gives enantiomerically enriched amine and amide products with either endocyclic or exocyclic chiral centers, e.g., 15 to give 16 (eq 15). Note that no decrease in enantiomeric excess is observed from substrate to product. In contrast, the intermolecular variant, e.g., reaction of 17 and 18 to give 19, conducted under identical reaction conditions, leads to products that are partially or fully racemized. Key to the success of the intermolecular process is the employment of bidentate ligands such as roc-BINAP or DPPF (eq 16). 

In these reactions, the nitrogen nucleophile is typically an amide, carbamate, or sulfonamide. Because of the low nucleophilicity of such nitrogen functions, no intermolecular 1,4-addition involving C—N bond formation is known. In all cases reported, the carbon-nitrogen coupling takes place in an intramolecular aminopalladation. 

General discussion of intra- and intermolecular interactions 3 van der Waals interactions 3 Coulombic interactions 5 Medium effects on conformational equilibria 5 Quantum mechanical interpretations of intramolecular interactions 7 Methods of study 8 Introduction 8 Nmr and esr spectroscopy 8 Microwave spectroscopy (MW) 12 Gas-phase electron diffraction (ED) 12 X-ray crystallographic methods 13 Circular-dichroism spectroscopy and optical rotation 14 Infrared and Raman spectroscopy 18 Supersonic molecular jet technique 20 Ultrasonic relaxation 22 Dipole moments and Kerr constants 22 Molecular mechanic calculations 23 Quantum mechanical calculations 25 Conformations with respect to rotation about sp —sp bonds 27 Carbon-carbon and carbon-silicon bonds 28 Carbon-nitrogen and carbon-phosphorus bonds 42 Carbon-oxygen and carbon-sulphur bonds 48 Conformations with respect to rotation about sp —sp bonds Alkenes and carbonyl derivatives 53 Aromatic and heteroaromatic compounds 60 Amides, thioamides and analogues 75 Conclusions 83 References 84... 

Sargeson and his coworkers have developed an area of cobalt(III) coordination chemistry which has enabled the synthesis of complicated multidentate ligands directly around the metal. The basis for all of this chemistry is the high stability of cobalt(III) ammine complexes towards dissociation. Consequently, a coordinated ammonia molecule can be deprotonated with base to produce a coordinated amine anion (or amide anion) which functions as a powerful nucleophile. Such a species can attack carbonyl groups, either in intramolecular or intermolecular processes. Similar reactions can be performed by coordinated primary or secondary amines after deprotonation. The resulting imines coordinated to cobalt(III) show unusually high stability towards hydrolysis, but are reactive towards carbon nucleophiles. While the cobalt(III) ion produces some iminium character, it occupies the normal site of protonation and is attached to the nitrogen atom by a kinetically inert bond, and thus resists hydrolysis. 

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