Imines aromatic

The alkylation of imines by an alkyl halide to give an iminium salt will be illustrated by selected reactions over a period of years. A more complete survey is available (88). Decker and Becker (89) prepared a number of iminium salts (91, for example) by mixing methyl iodide and aromatic imines in benzene. 2,5-Dimethyl-2-pyrroline (92) has been alkylated and the... 

Moreover, a dramatic increase of the reaction rate was observed when the coupUng of aromatic imines mediated by samariiun diiodide was carried out in the presence of both water and a tertiary amine or tetramethylethylene-diamine (TMEDA) [29], causing the almost instantaneous formation of the 1,2-diamine, although with undetermined diastereoselectivity. Similarly, the samarium diiodide promoted reductive coupling of iminiiun ions formed in situ by reacting ahphatic aldehydes with secondary amines and benzotriazole occurred at temperatures as low as - 70 °C [30]. Even in this case a mixture of diastereomers with undetermined ratio was obtained nevertheless, the item of diastereoselectivity induced by a chiral amine (auxiliary) is worthy of investigation. 

An approach to the preparation of asymmetrically 1,2-disubstituted 1,2-diamines has been reported the zinc-copper-promoted reductive coupling of two different N-(4-substituted)phenyl aromatic imines, one bearing a 4-methoxy and the other a 4-chloro substituent, in the presence of either boron trifluoride or methyltrichlorosilane, gave a mixture of the three possible 1,2-diamines, where the mixed one predominated [31 ]. Low degrees of asymmetric induction were observed using 1-phenylethylamine, phenylglycinol and its 0-methyl ether, and several a-amino acid esters as the chiral auxiharies meanwhile the homocoupling process was not avoided (M.Shimizu, personal communication). 

The asymmetric synthesis of unsymmetrical vicinal diamines by samarium diiodide induced reductive coupling of nitrones derived from aUphatic aldehydes with optically pure N-tert-butanesulfinyl aromatic imines has been recently reported [41]. For example, the reaction between nitrone 55 and... 

Similarly, the reaction of nitro compounds with the M-Boc aromatic imines 86 occurred in the presence of the enantiopure protic catalyst 87, which is a white, crystalline bench-stable salt [52] (Scheme 15). The reactions of ni-tromethane, very slow at - 20 °C, were accelerated in the presence of 10 mol % of 87, and the /3-amino compounds 88 were obtained with moderate yields and moderate to high enantioselectivities. Positive results were also obtained in the corresponding reactions of nitropropane to give the products 90. Hence, the primary diamines 89 and 91 are available by this route, which is advantageous for the significantly lower cost and toxicity of the catalyst and its easy removal from the reaction mixture simply by a basic wash. These results should stimulate further research on the development of new acid-catalyzed systems. 

The asymmetric Strecker-type reaction developed by the Jacobsen group is suitable for both aUphatic and aromatic imines, giving high enantiomeric excesses for a wide range of substrates. In this reaction the urea derivative also acts as the catalyst (Scheme 36). 

PreUminary studies on the racemic reaction of protected imines with ni-tromethane showed that the thiourea and the amine mutually weakened their reactivities. However, the bifunctional amino-thiourea led to good results. Enantioselectivity of the adduct depended on the protecting group, P(0)Ph2 affording the best results (76% ee). Then, other aromatic imines substrates were successfully phosphorylated with good to high enantioselec-tivities (63-76% ee). 

The stereoselective allylation of carbon-nitrogen multiple bonds have also been studied. The addition of allylzinc bromide to aromatic imines derived from (. S j-valine esters was affected by reversibility, which caused the lowering of the diastereoisomeric ratio with increasing reaction time. The retroallylation reaction could be avoided by performing the reaction in the presence of trace amounts of water or by using CeC - 7H2O as the catalyst with a decreased reaction rate.71... 

The groups of Loupy and Jun have presented a chelation-assisted rhodium(I)-cata-lyzed ortho-alkylation of aromatic imines with alkenes (Scheme 6.57) [119]. The use of 2 mol% of Wilkinson s catalyst, RhCl(PPh3)3, and 5 equivalents of the corresponding alkene under solvent-free conditions proved to be optimal, providing the desired ortho-alkylated ketones in high yields after acidic hydrolysis. Somewhat lower yields were obtained when the imine preparation and the ortho-alkylation were realized in a one-pot procedure. 

Secondary amines such as 45 have been made with up to 65% ee, while aromatic imines of the type shown in 46 give products with up to 39% ee... 

Table 22 Asymmetric hydrogenation of acyclic aromatic imines ...

Indenones can be synthesized from the carbonylation of aromatic imines (Equation (111)).102... 

Aromatic imines can be ortho-arylated and alkenylated using ruthenium catalysis (Equation (129)).1... 

Nitrogen functionality also assists the alkylation of ortho-Cr-H bonds of aromatics, as shown in Equations (10)—(12). In the case of aromatic imines, Ru3(GO)i2 exhibits a high catalytic activity.8-10 This reaction gives the alkylation product together with the alkenylation product in the reaction with triethoxyvinylsilane. Rhodium catalysts show the same activity to give the alkylation product.11,12,12a For example, the Rh(i)-catalyzed reaction of the imine of aromatic ketones with methyl acrylate... 

The regioselective arylation occurs when the reaction of 2-arylpyridines with aryl halides is conducted with the aid of the ruthenium(ii)-phosphine complex as catalyst (Equation (66)).81 The ortho-position to the 2-pyridyl group is arylated predominantly. The aromatic imines are also arylated with the same catalytic system.82... 

The catalytic arylation of alkane moiety also occurs in the reaction of an aromatic imine bearing tert-butyl group with Ph2Si(OH)Me under a Pd(OAc)2/Cu(OAc)2/BQ catalysis (Equation (69)).86,86a... 

The assumed mechanism includes the activation of acetonitrile by iV-coordination to the metal center, followed by deprotonation with DBU. The generated carbanion, iV-coordinated to the ruthenium atom, adds to the corresponding electrophile, while the presence of the sodium salt allows the regeneration of the ruthenium catalyst. Both various types of aldehydes as well as activated aromatic imines have been successfully employed as electrophiles, providing the corresponding adducts 171 in good to high yields. 

Asymmetric aza Diels-Alder reactions provide a useful route to optically active heterocyclics such as piperidines and tetrahydroquinolines.45 Although successful examples of diastereoselective approaches had been reported as early as 10 years ago,46 only recently have enantioselective reactions been accomplished.47 For example, the reaction of chiral amine-derived aromatic imine 115 with Brassard s diene 116 gives adduct 117 with up to 95% diaster-eoselectivity (Scheme 5-37).48... 

Substituents on imino nitrogen influence both reactivity and enantioselectivity in hydrogenation of imino compounds. Figure 1.32 shows two successful examples. An f-BINAPHANE-Ir complex effects asymmetric hydrogenation of A-aryl aromatic imines.On the other hand, an Et-DuPHOS-Rh complex (see Figure 1.2) is effective for hydrogenation of A-acyUiydrazones. ... 

The asymmetric Mannich addition of carbon nucleophiles to imines catalyzed by the cyclohexane-diamine catalysts has developed significantly in the past decade. List and co-workers reported the asymmetric acyl-cyanantion of imines catalyzed by a cyclohexane-diamine catalyst [103], Using a derivative of Jacobsen s chiral urea catalyst, the authors optimized reaction conditions and obtained chiral iV-acyl-aminonitriles in high yield and enantioselectivities (Scheme 51). The scope of the reaction was explored with both aliphatic and aromatic imines, providing good to high selectivities for a variety of substrates. 

The chiral guanidine s role as a strong Brpnsted base for the reactions of protic substrates has been proposed. In 1999, Corey developed a C -symmetric chiral guanidine catalyst to promote the asymmetric Strecker reaction [117]. The addition of HCN to imines was promoted high yields and high enantioselectivities for both electron-withdrawing and electron-donating aromatic imines (Scheme 64). 

The radical-anion intermediates derived from aromatic imines behave as nucleophiles towards carbon dioxide, as with 48 [190,191]. Ibis nudeophic character is enhanced by reduction in the presence of chlorotrimethylsilane. A carbanion... 

Scheme 6.86 Typical 2-aryl-2,5-dihydropyrrole derivatives prepared with the asymmetric [3 + 2] cycloaddition between buta-2,3-dienoic acid ethyl ester and various DPP-protected (hetero)aromatic imines catalyzed by phosphinothiourea 75.

Scheme 6.182 Representative products obtained from the 222-catalyzed aza-Henry reaction of N-Boc-protected aromatic imines with nitromethane and nitroethane.

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