Aldimines selectivity

A-2 (aldimine- selective) ScCI3, FeCI3, lnCI3, BiCI3... 

It is well recognized fhat aldimines are less reactive than aldehydes toward nucleophilic addition. In the presence of a catalytic amount of Yb(OTf)3, however, silyl enolates react with aldimines exclusively to afford / -aminocarbonyl compounds in high yield, even when aldehydes are present (Scheme 10.74) [209]. Selective formation of aldimine-Yb(OTf)3 complexes rather than aldehyde-Yb(OTf)3 complexes is attributable to fhe inverted reactivity. Polyallylscandium trifylamide ditriflate (PA-Sc-TAD), a polymer-supported Sc catalyst, also has high aldimine-selectivity. 

Formation of an aldimine intermediate is the first step in the catalytic hydrogenation of nitriles. When hydrogenation is carried out in aqueous acidic media, aldehydes may form by hydrolysis of the aldimine. Selective hydrogenation of aromatic nitriles to ben-zaldehydes over finely divided Ni (Raney Ni) is best obtained with an equimolecular amount of H2SO4 in a 10 1 mixture of tetrahydrofuran-water ... 

These aldimine-selective reactions using the polymer-supported catalyst will be applied to other nucleophilic addition reactions in organic chemistry. 

Interestingly, the diastereofacial selectivity can be reversed in the Strecker reaction of aldimines derived from galactosylamine 1 by simply changing the solvent. When the reaction of trimethylsilyl cyanide with the Schiff bases 2 catalyzed by zinc chloride, is carried out in chloroform instead of 2-propanol, there is a preferred formation of the (.S)-amino nitrile diastereomers63. 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

The reaction can be performed in one flask with great operational ease a mixture of an aldehyde and p-anisidine is stirred in THF for 5-10 h at 50 °C. Then, without removing the water produced, Ni(acac)2, isoprene, and Et2Zn are added in this order at room temperature. The mixture is stirred at the same temperature for the period of time indicated (Table 8). The products 57 and 58 are isolated as a mixture by column chromatograph after the usual work-up. Table 8 demonstrates the scope regarding the kind of aldehyde that encompasses not only aromatic aldehydes but also aliphatic aldehydes and even the parent formaldehyde. Despite the diminished electrophilic reactivity of aldimines, the reaction is complete at room temperature within a reasonable reaction time. The reaction of aldimines proceeds in an opposite sense of stereoselectivity to that of aldehydes and selectively provides 1,3-syn isomers 57. 

Selective cyclization of an alkenyl imine is catalyzed by trimethylsilyl triflate (Scheme 76).329 /-Butyldimethylsilyl triflate ( BuN SiOTf) catalyzes imino Diels-Alder reactions of TV-phenyl-aromatic aldimines to afford exo adducts preferentially.330 When A1C13 is used instead of Bufv SiOTf, endo adducts are obtained predominantly. 

Asymmetric reactions have also been developed. The reactions of allyltitaniums with chiral aldimines derived from optically active 1-phenylethylamine afford optically active homoallylic amines with excellent diastereofacial selectivities. Thus, the Cram syn addition products are obtained highly predominantly when using crotyltitanium reagent 33, as exemplified in Scheme 13.30 [61]. 

Binding of pyridoxal phosphate to peptide PP-42 also appears to be selective for lysine 30. As was indicated by NMR spectroscopy and UV/vis experiments, only one of three potential lysine Schiff bases appeared to form. To determine the site or sites of attachment, the aldimine peptide intermediates were reduced, proteolytically cleaved, and the fragments analyzed by mass spectroscopy. This... 

In 2006, Akiyama and coworkers established an asymmetric Brpnsted acid-catalyzed aza-Diels-Alder reaction (Scheme 36) [59]. Chiral BINOL phosphate (R)-3o (5 mol%, R = 2,4,6- Pr3-CgH2) bearing 2,4,6-triisopropylphenyl groups mediated the cycloaddition of aldimines 94 derived from 2-amino-4-methylphenol with Danishefsky s diene 95 in the presence of 1.2 equivalents of acetic acid. Piperidinones 96 were obtained in good yields (72 to >99%) and enantioselectivi-ties (76-91% ee). While the addition of acetic acid (pK= 4.8) improved both the reactivity and the selectivity, the use of benzenesulfonic acid (pK= -6.5) as an additive increased the yield, but decreased the enantioselectivity. A strong achiral Brpnsted acid apparently competes with chiral phosphoric acid 3o for the activation of imine 94 and catalyzes a nonasymmetric hetero-Diels-Alder reaction. The role of acetic acid remains unclear. 

The groups of Rueping [25] and Gong [26] have developed the aza-hetero-Diels-Alder reaction of aryl imines and cyclohexenone to give isoquinuclidines in good endojexo selectivities and high yields and ee s by 1 and la, respectively (Scheme 5.13). In the presence of acid, cyclohexenone enolizes to afford the dienol which subsequently undergoes a Mannich reaction with the protonated aldimine followed by intramolecular aza-Michael addition to produce the formal Diels-Alder adducts. 

In related studies, Terada described the synthesis of optically pure piperidines via a tandem aza-ene-type reaction/cyclization sequence (Scheme 5.18) [32]. The reaction of a monosubstituted enecarbamate and an N-acyl aldimine affords aza-ene-type intermediate 5, which reacts with a second equivalent of enecarbamate to give aldimine 6. Subsequent intramolecular cyclization terminates the aze-ene-type reaction sequence to furnish trans-piperidine 7 in high enantio- and diasterio-selectivities. 

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