Addition of Organometallic Reagents to Imines

The nucleophilic addition of organometallic reagents to imines provides an attractive route to amines [4]. Recendy, however, some completely different approaches to the synthesis of a-aryl amine were reported. Hayashi and Ishigeda-ni found a new catalytic system for the asymmetric addition of arylstannanes to imines derived from aromatic aldehydes (Scheme 11) [20]. 

Addition of organometallic reagents to imines is not limited to allylmetal derivatives. Hoveyda and Snapper have demonstrated that dialkylzinc reagents can add to imines in a one-pot procedure. Using a zirconium complex as metal catalyst and a chiral peptide, diverse enantioenriched aryl, aliphatic and alkynyl amines 142 have been obtained with high levels of enantioselectivity (Scheme 8.60) [136],... 

Asymmetric addition of organometallic reagents to imines, to produce useful optically active amines, has been reviewed.44... 

The addition of organomagnesium reagents to imines and nitriles is an important method for the synthesis of primary amines. The addition of RMgX to imines is rather complex, and the result depends on the nature of the reagents. A stoichiometric amount of a Lewis acid can be added to enhance the rate of the addition and the 1,2-selectivity. The addition of organometallic reagents to imines has been reviewed. ... 

The addition of organometallic reagents to the C —N double bond of imines 1 provides an attractive route to amines 21 2. However, due to the poor electrophilici ty of imines, this method is often plagued by competitive reactions ... 

The enantioselective addition of organometallic reagents to, V-(trimethylsilyl)benzaldehyde imine (1) in the presence of enantiomerically pure modifiers has been investigated. The best result is obtained with butyllithium (the corresponding Grignard reagent affords both lower yield and selectivity, 1 fails to react with diethylzinc) and two equivalents of the enantiomerically pure diol 2 in diethyl ether. It should be noted that the choice of the solvent is crucial for the stereoselectivity of the reaction1 2 3 5 7 8 9. 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

By constructing rigid endocyclic imines/imine derivatives (either isolated or generated in situ) some of the problems associated with acyclic stereocontrol can be avoided. The addition of organometallic reagents to 3-thiazolines (16) or tiie putative piperidine intermediate (17) provides excellent stereocontrol. 

Table 2 The Addition of Organometallic Reagents to Activated Imines Containing a-Hydrogen Atoms...

While the addition of organometallic reagents to acyclic or cyclic imines (43) is often compromised by poor imine reactivity, these reagents readily condense with structurally diverse, more electrophilic imini-um salts (44), bearing a positive charge on the nitrogen atom, to provide substituted tertiary amines (45 Scheme 6). A review of the literature describing additions to cyclic iminium salts prior to 1966 is avail-... 

For a recent review on the ligand-mediated addition of organometallic reagents to azome-thine fimctions, see Denmark SE, Nicaise OJ-C (1996) Chem Commun 999 For a recent review on the catalytic, enantioselective addition to imines, see Kobayasni S, Ishitani H (1999) Chem Rev 99 1069... 

The addition of organometallic reagents to aldimines derived from chiral amines provides another option (unique to imines) for controlling reaction diastereofacial selectivity. Yamamoto et have... 

The addition of a variety of organometallic reagents to imines and hydrazones (74) of 2-acyl-1,3-oxathianes derived from pulegone proceeds with very high diastereoselectivity (Equation (39)), the addition of lanthanide salts reversing the sense of asymmetric induction <90JA8189,94CL831). 

As for C-C bond formation via an addition of organometallic reagent to aldehyde, ketone or imine or allylation, supported-complexes of prolinol, ephedrine and oxazoline derivated constitute the best catalytic systems. 

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