Nucleophilic alkenoylation

The nucleophilic alkenoylation of a-phenyl-substituted aldehydes and ketones with (methyl-substituted) [l-cyano-l-(trimethylsilyloxy)-2-propenyl]lithium proceeds with good 1,2-induction to afford the j> i-hydroxy ketones109. 

Based on our previous results on the nucleophilic alkenoylation of aldehydes via metallated a, 3-unsaturated aminonitriles [50], we now envisaged an enanti-oselective variant. Thus, the enantiopure a-aminonitriles 60 were metallated with LDA and by reaction with aldehydes the adducts 61 could be obtained. Subsequent cleavage of the aminonitrile function with silver nitrate led to the desired a -hydroxyenones 62 in overall yields of 29-80% and enantiomeric excesses ee of 50-69%. Alternatively, the conjugate addition of the lithiated aminonitrile 63 to t-butyl crotonate led to the y-keto ester 63 in 35% yield and an enantiomeric excess ee of >90% (Scheme 1.1.18). 

The influence of the amount of amine can be elucidated by mechanistic considerations of the double carbonylation. An allyl halide readily forms an allypalladium halide by oxidative addition to Pd(0) species and the amine can attack the allyl ligand to generate allylamine. However, the nucleophilic attack is a reversible process and CO insertion into the allylpalladium species can take place in the presence of a small amount of amine to allow the formation of the acylpalladium species. Attack of the amine on the coordinated CO giving the carbamoylpalladium species followed by reductive elimination by coupling with another alkenoyl ligand produces the a-keto amide [132],... 

NMR and IR analysis revealed an intramolecular hydrogen-bonding interaction between the NH of the imide and the methojgr group of the aromatic ring. This interaction is believed to enhance the electrophilicity of the N-alkenoyl moiety of the imide since the electron density of the nitrogen atom is decreased. Furthermore, thiourea 15 was able to catalyse the subsequent 1,2-addition of hard nucleophiles to the resulting dicyano benzamides. 

Another auxiliary that became well known in enolate chemistry is chiral acyl iron complexes for alkylation, aldol reactions, and conjugate additions indeed, so-called Davies-Liebeskind enolates [60] can be generated either by deprotonation of alkanoyl complexes 124a or conjugate addition of strong nucleophiles like alkyllithium compounds or lithium amides to alkenoyl complexes 127. 

They subsequently found that N-alkenoyl-2-methoxybenzamide was the best substrate among the corresponding benzamides [87]. Several active methylene compounds could be employed as nucleophiles to give the Michael adducts in good to excellent yields with up to 93% ee (Scheme 2.36). 

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