Organometallic reagents, alternative

In his original paper,2 Cram disclosed an alternative model that rationalizes the preferred stereochemical course of nucleophilic additions to chiral carbonyl compounds containing an a heteroatom that is capable of forming a complex with the organometallic reagent. This model, known as the Cram cyclic or Cram chelate model, has been extensively studied by Cram9 and by others,410... 

Organopalladium intermediates are also involved in the synthesis of ketones and other carbonyl compounds. These reactions involve acylpalladium intermediates, which can be made from acyl halides or by reaction of an organopalladium species with carbon monoxide. A second organic group, usually arising from any organometallic reagent, can then form a ketone. Alternatively, the acylpalladium intermediate may react with nucleophilic solvents such as alcohols to form esters. 

Free radical addition to oximes and oxime ethers emerged as a useful alternative to addition of organometallic reagents, particularly for intramolecular reactions. The most important advantage of free radical V5. organometallic addition is its tolerance for almost any functional group (with the exception of thiocarbonyl and iodoalkyl functions). 

Alternative synthetic approaches include enantioselective addition of the organometallic reagent to quinoline in the first step of the synthesis [16], the resolution of the racemic amines resulting from simple protonation of anions 1 (Scheme 2.1.5.1, Method C) by diastereomeric salts formation [17] or by enzymatic kinetic resolution [18], and the iridium-catalyzed enantioselective hydrogenation of 2-substituted quinolines [19]. All these methodologies would avoid the need for diastereomer separation later on, and give direct access to enantio-enriched QUINAPHOS derivatives bearing achiral or tropoisomeric diols. Current work in our laboratories is directed to the evaluation of these methods. 

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