Alkylation Reactions with Imidazolidinone Enamines

In a similar approach, MacMillan reported an operationally simple procedure for the enantiocontrolled C-F bond formation. The enantiose-lective a-fluorination of aldehydes was based on the use of imidazolidinone I as the active catalyst. MacMillan proposed the use of M-fluorobenzene-sulfonimide 3 (NFSI) as a fluorinating agent (Seheme 18.5 B). A similar mechanism has been proposed for both ehlorination and fluorination with the MaeMillan eatalyst, in which the imidazolindinone enamine reacts with the halogen source, although this mechanism has not been proven 

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Alkylation of aldehydes with enol silyl ethers is accomplished on oxidation of the latter species with CAN. By forming chiral enamines from the aldehydes and the imidazolidinone 20 in situ the reaction furnishes optically active products. ... 

Nucleophilicity parameters N and % for electrophile-nucleophile combination based on the Mayr equation log k=+E) were reported for fluorides in protic solvents, enamines derived from imidazolidinones, trimethylsilyl enol ethers with perfluori-nated substituents at the a-carbon, O-methylated Breslow intermediates, anions of nucleobases and their subunits, enamides, symmetrical and unsymmetrical hydrazines, and heteroarylboron compounds. Of note, replacement of CH3 with CF3 and C6H5 with CgF5 in the trimethylsilyl enol ethers reduces the nucleophilicity by 8 and 4.5 orders of magnitude, respectively. Hydrazines have very similar nucle-ophilicities to alkyl amines in other words, there is no evidence of an a-effect. With NH2NMC2, there is a fast reversible reaction corresponding to addition of the tertiary amine, followed by a slow irreversible reaction for addition at the primary amine, with a 3000-fold difference in nucleophilicity between the two sites. ... 

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