Aromatic aldimines

GattermaDD synthesis A method for the synthesis of aromatic hydroxyaldehydes. E.g. AICI3 is used to bring about the condensation of phenol with a mixture of gaseous hydrochloric acid and hydrocyanic acid an aldimine hydrochloride is formed and on hydrolysis gives p-hydroxybenzaldehyde... 

With Aromatic Aldehydes. To a solution of 10.3 g (20 mmol) of 2,3,4,6-tetra O-pivaloyl-/ -i>galactopyra-nosylaminc in 50 rnL of /-PrOI 1 or heptane are added 30 mmol of the corresponding aromatic aldehyde and 30 drops of acetic acid. After 30 min to 2 h, the Schiff base precipitates from the /-PrOH solution. When the reaction is carried out in heptane, 2 g of Na2S04 or 3 g of 3 A molecular sieves are added after 15 min, and the mixture is filtered. On cooling to 0 °C the Schiff base crystallizes from the heptane solution. The aldimines are collected by filtration and rapidly washed with ice-cold /-PrOH or pentane, respectively. Generally, they are pure enough for further transformations. 

In a related reaction, isocyanides can be converted to aromatic aldimines by treatment with an iron complex followed by irradiation in benzene solution RNC -I- CftHe PhCH=NR. ... 

Reductive coupling of aldimines obtained from aromatic aldehydes and aromatic amines to generate vicinal diamines mediated by indium was carried out in aqueous ethanol (Eq. 11.59)." Small indium rods were used in this study. No side-product was observed due to unimolecular reduction. The presence of NH4CI was found to accelerate the reaction. The reaction fails completely in CH3CN, DMF, or wet DMF. The use of nonaromatic substrates also resulted in the failure of the reaction. 

In general, an aldimine is among the least reactive carbonyl compounds and is by far less reactive than an aldehyde [31-33]. Nevertheless, the Et2Zn-Ni catalytic system is successfully extended to the homoallylation of aldimine. Aldimine prepared in situ from an aldehyde and a primary aromatic amine undergoes the homoallylation smoothly under the essentially identical con-... 

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. 

Intramolecular process with rhodium catalyst has been described for the syntheses of indane, dihydroindoles, dihydrofurans, tetralins, and other polycyclic compounds. Wilkinson catalyst is efficient for the cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered to the K z-position of the imine-directing group. 

Aldimines derived from aromatic aldehydes suffered hydrogenolysis in hydrogenation over palladium at 117-120° at 20 atm and gave products in... 

Akiyama et al. disclosed an asymmetric hydrophosphonylation in 2005 (Scheme 32) [55], Addition of diisopropyl phosphite (85a) to A-arylated aldimines 86 in the presence of BINOL phosphate (R)-M (10 mol%, R = 3,5-(CF3)j-C Hj) afforded a-amino phosphonates 87 in good yields (72-97%). The enantioselectivities were satisfactory (81-90% ee) in the case of imines derived from a,(3-unsaturated aldehydes and moderate (52-77% ee) for aromatic substrates. 

The same group expanded the scope of the aza-Diels-Alder reaction of electron-rich dienes to Brassard s diene 97 (Scheme 37) [60]. In contrast to Danishefsky s diene, it is more reactive, but less stable. Akiyama et al. found chiral BINOL phosphate (R)-3m (3 mol%, R = 9-anthryl) with 9-anthryl substituents to promote the [4 + 2] cycloaddition of A-arylated aldimines 94 and Brassard s diene 97. Subsequent treatment with benzoic acid led to the formation of piperidinones 98. Interestingly, the use of its pyridinium salt (3 mol%) resulted in a higher yield (87% instead of 72%) along with a comparable enantioselectivity (94% ee instead of 92% ee). This method furnished cycloadducts 98 derived from aromatic, heteroaromatic, a,P-unsaturated, and aliphatic precursors 94 in satisfactory yields (63-91%) and excellent enantioselectivities (92-99% ee). NMR studies revealed that Brassard s diene 97 is labile in the presence of phosphoric acid 3m (88% decomposition after 1 h), but comparatively stable in the presence of its pyridinium salt (25% decomposition after 1 h). This observation can be explained by the fact that the pyridinium salt is a weak Brpnsted acid compared to BINOL phosphate 3m. 

Historically, the amine was an aromatic amine but is now generalized to any amine. A Schiff base, also called an aldimine, is formed in the pyridoxal 5-phosphate-dependent aminotransferase reactions. 

Examples of the Bronsted-acid catalysts and hydrogen-bond catalysts are shown in Figure 2.1. We have recently reported the Mannich-type reaction of ketene silyl acetals with aldimines derived from aromatic aldehyde catalyzed by chiral phosphoric acid 7 (Figure 2.2, Scheme 2.6) [12]. The corresponding [5-amino esters were obtained with high syn-diastereoselectivities and excellent enantioselectivities. 

Later in 2007, Gong utilized If and saturated derivative 2 in a direct Mannich reaction between in situ generated N-aryl imines and cyclic ketones as well aromatic ketones (Scheme 5.3) [10], It was found that electron poor anilines as coupling partners gave the highest enantioselectivities. The authors postulate that acid promoted enolization of the ketone forms the reactive enol which adds to the protonated aldimine. 

In previous work, Corey used the free base form of 34 as an effective chiral ligand in the Os04-promoted dihydroxylation of olefins [90]. He later found that ammonium salt 34 catalyzed the addition of HCN to aromatic N-allyl imines (Scheme 5.50) [91]. The U-shaped pocket of the catalyst is essential in fixing the orientation of the hydrogen-bonded activated aldimine via n-n interactions. 

Scheme 6.40 Product range of the 11-catalyzed asymmetric Strecker reaction of aromatic and aliphatic N-allyl-protected aldimines.

Scheme 6.41 Typical products obtained from the asymmetric Strecker reaction of aliphatic and aromatic aldimines catalyzed by urea 42.

List and co-workers reported the 47-catalyzed (lmol% loading) asymmetric acetylcyanation of N-benzyl-protected aliphatic and aromatic aldimines by using commercially available liquid acetyl cyanide as the cyanide source instead of HCN [161]. Under optimized reaction parameters (toluene, -40 °C) the procedure resulted in the desired N-protected a-amino nitriles 1-5 in yields ranging from 62... 

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