Mechanistic with aldimines

New catalyst design further highlights the utility of the scaffold and functional moieties of the Cinchona alkaloids. his-Cinchona alkaloid derivative 43 was developed by Corey [49] for enantioselective dihydroxylation of olefins with OsO. The catalyst was later employed in the Strecker hydrocyanation of iV-allyl aldimines. The mechanistic logic behind the catalyst for the Strecker reaction presents a chiral ammonium salt of the catalyst 43 (in the presence of a conjugate acid) that would stabilize the aldimine already activated via hydrogen-bonding to the protonated quinuclidine moiety. Nucleophilic attack by cyanide ion to the imine would give an a-amino nitrile product (Scheme 10). 

Leaving precise mechanistic arguments aside, it should be stressed that an a,/9-unsatu-rated carbonyl compound can behave as a latent nucleophile with the assistance of a hydrosilane and a low-valence rhodium complex. With this simplification, isocyanates 18 and aldimines 20 were used as electrophiles for a similar protocol. Both were successfully incorporated with the aid of [Rh(COD)(P(OPh)3)2]OTf to afford 19 and 21, respectively (Scheme 6.5) in a reaction that was similar to the aldol-type coupling [11]. 

Very recently further optimization was achieved on the basis of rational mechanism-driven optimization (for this mechanistic study [12], see the corresponding section below). The resulting, further improved catalyst 10b was found to be superior to 9 and 10a, and is the most enantioselective Strecker catalyst yet prepared [12]. Starting from both aliphatic and aromatic aldimines, excellent enantioselectivity in the range 96-99.3% ee was obtained even in the presence of only 1 mol% 10b. An overview of the excellent enantioselectivity obtained with 10b, and comparison with ee values obtained in the presence of catalyst 10a, are given in Scheme... 

From their extensive mechanistic studies on the asymmetric dihydroxylation reaction, the Corey group extended the utility of these catalysts to the Strecker reaction.35 Treatment of their dihydroxylation catalyst with trifluoroacetic acid generated a stable crystalline solid 63 that was demonstrated to catalyze the asymmetric Strecker reaction. The TV-allyl moiety was found to be preferred to benzyl as a protecting group for the nitrogen atom. Thus, when 64 was treated with catalyst 63, nitrile product 65 could be obtained in excellent yield. A solvent effect on the % ee was noted such that CH2CI2 was optimal compared to toluene that may compete with the aldimine for the catalyst s binding site. 

Pyruvyl-dependent amino acid decarboxylases are mechanistically analogous to the PLP-dependent amino acid decarboxylases wherein a pyruvyl group in amido linkage to the amino terminus of the protein functions in place of PLP. The formation of a Schiff base linkage between the a-amino function of the amino acid and the ketonic carbonyl of the pyruvyl moiety is supported by the results of borohydride trapping experiments with L-histidine decarboxylase Lactobacillus 30a) in the presence of substrate (265). Evidence could not be found for a reducible internal aldimine in the absence of substrate. 

All known reactions of PLP-containing enzymes can be described mechanistically in the same way-formation of a planar Schiff base or aldimine intermediate, followed by formation of a resonance-stabilized carbanion with a quinoid structure, as shown in Figure 20,15. Depending on the bond labilized, formation of the aldimine can lead to a transamination (as shown in Figure 20.15), to decarboxylation, to racemization, or to numerous side chain modifications. 

In 2002, Jacobsen s group reported an improved analogue for the as5mimetric Strecker reaction based on detailed mechanistic studies. Both aldimines and ketimines underwent hydrocyanation with high enantioselectivities utilising thiourea 4 in just 1 mol% catalyst loading (Scheme 19.4). 

The lithium enolate of t-amyl acetate exists as a doubly chelated dimer in the presence of TMEDA (A,A,A, At -tetramethylethylenediamine). Reaction with a simple aldimine such as pflra-F-C6H4-CH=N-Ph gives an iV-lithiated -amino ester as a monomer, observed by Li- and i N-NMR. Kinetic studies by i F-NMR give a reaction order consistent with a TS of stoichiometry [(ROLi)2(TMEDA)2(imine)], supported by DPT calculations. That such aza-aldol condensations involve dimeric mechanistic routes runs counter to many claims that monomers are more reactive. 

Following advances made in reduction reactions (vide supra), hydroboration and diboration have been the subject of intense investigation with NHC-Cu catalysts. Early work by Sadighi revealed that [(ICy)Cu(Ot-Bu)] efficiently catalyzed the 1,2-diboration of aldehydes. Mechanistic studies permitted to rationalize a number of features of this reaction and notably ruled out a possible oxidative addition pathway to favour c-activation of the diboron reagent by the copper centre. [(ICy)Cu(Ot-Bu)] was also used for the diaster-eoselective diboration—in fact, hydroboration after work-up—of sulfinyl aldimines. ... 

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