Aldi mines

Zon, J., Asymmetric addition of tris(trimethylsilyl) phosphite to chiral aldi-mines, Pol.. Chem., 55, 643, 1981. 

Mechanistically, transamination by the free coenzyme proceeds through a number of discrete steps as illustrated in Fig. 3. The first step of the process, aldi-mine formation (Fig. 3, Step I), is common to all pyridoxal-dependent reactions. The rate and extent of this reaction are influenced by factors including reactant concentrations, the nature of the amino acid, pH, and solvent. However, it is important to realize that the coenzyme itself facilitates Schiff base formation in... 

Compounds of the composition [ReOCl3(N N)] have also been isolated with pyridine-2-aldi-mine and rr-acidic arylazopyridine and arylazoimidazole ligands." The products (101) are readily reduced by oxygen atom transfer reactions from Re to phosphorus atoms of phosphines which results in the formation of rhenium(III) complexes. Depending on the reaction condition and the phosphines used either mononuclear or binuclear compounds are formed." " Azo splitting reactions with arylazopyridines give access to arylimido and binuclear oxo/imido com-plexes. "" ... 

Highly enantioselective Mannich-type reactions of A-(2-hydroxyphenyl) aldi-mines with ketene trimethylsilyl acetals and of A-Boc-aldimines with acetyl acetone or furan are catalyzed by chiral phosphonic acids 9 derived from 3,3 -diaryl-(l )-BlNOL and POCI3 (Scheme 12.7). ... 

Terada et al. found the direct Mannich reaction between iV-Boc-protected aldi-mines 11 and acetyl acetone (12) to be catalyzed by different phosphoric acids 3 (Scheme 6). Varying the aromatic groups at the 3,3 -positions influenced the yields slightly (88-99%), but the enantioselectivities to a high degree (12-95% ee). 

Jew, Park and coworkers performed systematic investigations to develop a more efficient system for the asymmetric synthesis of a-alkylalanines by chiral phase-transfer catalysis [31]. Eventually, sterically more demanding 2-naphthyl aldi-mine tert-butyl ester 14 was identified as a suitable substrate, and its alkylation in the presence of stronger base rubidium hydroxide (RbOH) and 0(9)-allyl-N-2, 3, 4 -trifluorobenzyldihydrocinchonidinium bromide (6a) at lower reaction temperature led to the highest enantioselectivity (Scheme 2.11). 

Aziridines can be obtained by Bi(OTf)3- or Sc(OTf)3-catalyzed reaction of aldi-mines with ethyl diazoacetate in ionic liquid [139]. Ethyl diazoacetate adds to the imine leading to intermediate 150 which cyclizes to give the aziridine 151. In most cases the reaction is highly stereoselective affording cis-aziridines predominantly (Scheme 8.63). 

Catalyst 119a was also tested for the addition of various activated aromatic aldi-mines with MVK and EVK at low temperature in THF as solvent (Table 5.16). 

PLP radical was proved by application of [2-2H]lysine and [2-13C]lysine instead of lysine 24 to the reaction mixture [38]. In the first experiment the EPR signal was narrowed in the second it was broadened. The involvement of PLP in the reaction was proven by ESEEM spectroscopy. By incubation of the aminomutase with lysine, SAM, and [4 -2H]PLP a prominent doublet centered at the Lamour frequency for 2H was recognized [39], in accordance with the structure of an external aldi-mine. These findings establish a new role for PLP in enzyme reactions - PLP facilitates the radical isomerization. 

Additions. Asymmetric Michael additions of Grig-nard reagents can be performed on a,p-unsaturated aldi-mines derived from either enantiomer of f-leucine f-butyl ester (eq 3). 

The first step involves Schifif base formation by the amino group of the substrate reading with pyridoxal phosphate to form an aldi-mine. This is followed by loss of a functional group (Rg, Equation 17.51), usually by abstraction by an active-site base, to form a resonance-stabilized carbocation. 

Other organometallic compounds, including aUylic stannanes, allylic samarium, allylic germanium, and allylic indium compounds add to aldi-mines in the same manner. Aryltrialkylstannanes also add the aryl group to Al-tosyl imines using a rhodium catalyst and sonication. Catalytic enantioselective addition reactions are well known, including reactions in an ionic liquid.Allylic... 

Isocyanides that do not contain an a hydrogen react with alkyllithium compounds, " as well as with Grignard reagents, to give lithium (or magnesium) aldi-mines These metalated aldimines are versatile nucleophiles and react with various substrates as follows ... 

To address the design criteria listed above, Kobayashi and co-workers prepared the mildly Lewis acidic zirconium[BINOL]2 complexes 78a,b from Zr(Of-Bu)4and (i )-BINOL and theimines 76 derived from 2-aminophenol [51a, 51b, 51c, 51d] (Scheme 26). In the presence of catalytic amounts of 78a the tri-methylsilyl ketene acetal of methyl 2-methylpropanoate (77) reacted with 76a to afford the adduct 79 quantitatively and with 34% ee. The use of N-methylim-idazole (NMI) in equal amoimts markedly improved the selectivity to 70% ee as did the use of 78b which provided 79 in 90% ee. By chemical correlation the products were shown to be of the i -configuration. The reaction displayed some generality with aromatic aldimines (83-98% ee), but the one enoHzable aldi-mine gave only modest results (56% yield, 80% ee) [51e]. 

Besides indole, the AFC reaction of other electron-rich arenes such as furan, pyrrole, naphthol, 4,7-dihydroindole, and substituted benzene with imines have been also well developed over the past years. Some examples are given in this section. Terada and co-workers reported that in the presence of 2 mol% of CPA (R)-13f, the AFC reaction of 2-methoxyfuran with iV-Boc aldi-mines underwent smoothly at -35 °C to afford furan-2-ylamine derivatives in 80-96% yields with 86-97% ee (Scheme 6.16). ... 

Wang and co-workers developed an AFC reaction of naphthols with aldi-mines employing a bifunctional modified cinchona alkaloid catalyst 48 (Scheme With 10 mol% 48, the reaction of naphthols with a wide... 

Scheme 2.5 Diastereo- and enantioselective direct Mannich-type reaction of aldi-mines with 1,3-dicarbonyl compounds with the use of chiral lithium(i) binaphtholate.

Synthesis of Amines One of the most common strategies for the synthesis of branched amines is the 1,2-addition of a nucleophile to the previously synthesized aldi-mines or ketimines. Avoiding the imine synthesis, though, is highly desirable. MCR-based methodologies toward this end have been developed. 

Ketimines are also the products of the reaction between t-butyl-lithium aldi-mine, an acyl anion equivalent derived from 1,1,3,3-tetramethylbutyl iso< anide and t-butyl-lithium, and aryl, vinyl, and acetylenic halides, which upon hydrolysis yield the corresponding ketones (Scheme 47). ... 

In the transamination reaction, formation of the aldi-mine intermediate between aspartate and PLP and its deprotonalion proceeds as described above for the race-mases. However, reprotonation occurs not at the same carbon as in the racemization mechanism but at a position adjacent to the PLP heterocycle. 

The first highly enantioselective reaction catalyzed by a chiral guanidine was reported by Corey and coworkers in 1999 [128], C2-symmetric guanidine 46 was shown to be a highly effective catalyst in the Strecker reaction of aromatic aldi-mines, affording the Strecker products in high yields and enantioselectivities (Scheme 10.43). 

Allylation of hydrazones derived from aryl alkyl ketones [56] and of N-aryl aldi-mines in DMF at 0°C [61] has also been reported. 

In 2007, Kunz presented a new class organocatalysts that consists of glycosyl amines and planar-chiral [2.2]paracyclophane derivatives [51]. Within this new class, N-galactosyl[2.2]paracyclophane carbaldimine 97 proved to be a valuable catalyst for the enantioselective Strecker reaction of aromatic (entries 1, 5) and aliphatic aldi-mines 96 (entries 2—4) (Table 30.13). Aromatic products were obtained in good yields (55-87%) and reasonable enantiopurities (71-82% ee), aliphatic substrates instead led to higher yields (84—89%) and better enantiopurities (88-99% ee). 

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