Imines, preparation

The imine, prepared from an amine and (C5H4N)(Me3C JH2)CO (TiC, toluene, reflux, 12 h NaOH, 80% yield), can be cleaved with coned. HCl (reflux). The protective group was used to direct a-alkylation of amines. 

Imine preparation from a tricarbonyl system followed by PPA promoted... 

In contrast to the amt-selective reaction of lithiated imines with aldehydes, titanated imines, prepared by transmetalation of the corresponding lithium azaenolates, give predominantly. sFH-adducts2. 

Instead, the reaction of TMS cyanide with the chiral imine prepared from racemic 2-benzoylaminocyclohexanone and (fi)-l-phenylethylamine or (S)-l-phenylethylamine in the presence of zinc chloride occurred with low stereocontrol, and the two enantiomers of fra s-l,2-diaminocyclohexane car-boxyhc acid were isolated with low yields after several steps [88]. 

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. 

Highly functionalized tetraaryl-4,5-dihydro-l,2,4-triazoles 118a-y have been prepared on a soluble polymer support (PEG4000) from the cycloaddition of diarylimines with a nitrile imine, prepared in situ from the arylhydra-zone 119. The triazole products are highly fluorescent and several have reasonable fluorescence quantum yields (Scheme 8 and Table 19) <2005S3535>. 

Reaction of oxazolones with 1-azadienes, for example, imines prepared from 3-(2-furyl)acrolein or cinnamaldehyde, affords 2-pyridones 316. Several mechanisms have been proposed to explain the formation of 316. However, products like 315 have also been isolated. The authors proposed that 315 arises from alkylation at C-4 of the oxazolone by the 1-azadiene. Subsequent nucleophilic attack by the amino group with ring opening then yields the 2-pyridone (Scheme 7.103). Representative examples of 2-pyridones prepared from 1-azadienes are shown in Table 7.28 (Fig. 7.30). 

Therefore, in principal, condensation of a primary amine with an enantiomerically pure ketone should allow asymmetric synthesis of a-substituted primary amines. This approach has been applied to the synthesis of a-amino acids, for example, using the imine prepared from a-amino esters and (l.S, 2,S ,5,S )-2-hydroxy-3-pinanone, via an amino-substituted ester enolate anion with some success39 40. Application of this approach to simple primary amines has seldom been reported. 

Also see preparation via hydrazones (Section 1.1.1.4.2.). b For imine preparation, see Table 1 (Section 1.1.1.4.1.1.). c Based on optical rotations unless otherwise indicated. d Recorded at 23 C in (C2H5)20 unless otherwise indicated. 

Organomagnesium compounds react with imines, prepared from 3-methoxy-2-naphth-aldehydes by a 1.4-addition mechanism. This reaction can be performed with high diastere-oselectivity. The method was applied for the synthesis of optically pure S-tetralones . Vinyhnagnesium bromide reacts as an acceptor with a ketone dimethyl hydrazone zincate 207, yielding a 1,1-bimetallic species, which can be reacted sequentially with two different electrophiles (equations 131 and 132) . The reaction proceeds via a metalla-aza-Claisen rearrangement, where the dimethylhydrazone anion behaves as an aza-allylic system . 

The physical constants of several other imines prepared by a similar procedure are shown in Table X. The aldimines listed in the Table can be obtained only if certain precautions are strictly observed [4b]. The method of Emerson, Hess, and Uhle [4c] could not be extended satisfactorily and the method described in Preparation 2-2 is a modification of the one described by Chancel [4d] for propylidenepropylamine. The reaction is best carried out by adding the aldehyde to the amine, without a solvent, at 0°C. When the order of addition is reversed, the yields are much lower. Potassium hydroxide is added at the end in order to remove the water formed during the reaction. The use of other drying agents such as potassium carbonate or magnesium sulfate failed to yield aldimines on distillation. The aldimines should always be distilled from fresh potassium hydroxide to yield water-white products. The aldimines are unstable and should be used within a few hours after their distillation otherwise polymeric products are obtained. 

This peracetic acid solution is added dropwise to an ice-cooled solution of 17.7 gm (0.1 mole) of the imine prepared above in 50 ml of methylene chloride. The reaction mixture is then stored at 0°C for 16 hr, washed in turn with 200 ml of ice water and 200 ml of a cold 20 % aqueous sodium bicarbonate solution. The organic layer is dried and the solvent is evaporated under reduced pressure. The residue is covered with 25 ml of ethanol and stored in a refrigerator overnight. 

Enantioselective alkylation of ketones. Chiral imines prepared from cyclic ketones and 1 on metalation and alkylation are converted to chiral 2-alkyleyclo-alkanones in 87-100% enantiomeric purity.1 The high cnantioselectivity is dependent on chelation of the lithium ion in the anion by the methoxyl group, which results in a rigid structure. 

The submitters employed a toluene solution of crude imine prepared in part B and obtained somewhat higher yields (90-95%). However, the checkers obtained yields in this range on one half the scale using isolated sulfonylimine. 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Few additions have been attempted using imines prepared from heterocyclic aldehydes and heterocyclic amines. In the one example reported l-(3-pyridyl)-5-(2-quinolyl)-l,2,3-triazoline is obtained in 70% yield after 21 hr.329... 

The first example of 1,2-asymmetric induction was reported by Yamamoto and cowork-ers with/V-propyIaldirn ines derived from a-phenylpropionaldehyde (equation 13). The reaction gave mainly the anti product135, consistent with a Felkin-Ahn addition. A 1,3-asymmetric induction took place with the imine prepared from 1-phenylethylamine and isovaleraldehyde, giving a somewhat lower 7 1 diastereoselectivity. 

Diphenyl tellurium oxide and imines prepared from 2-hydroxybenzaldehyde and ethy-lenediamine reacted in benzene to produce a diphenyl tellurium phenoxide7. 

The imine, prepared in the usual way from a carbonyl compound and a primary amine, can be converted into the tertiary enamine by direct N-alkylation to tertiary iminium salt, which can be converted into the corresponding enamine by base181-183 (equation 5). 

For the synthesis of the trans-mmulsitQd 4a- p/-pumiliotoxin C 195 (Scheme 10.66), the imine prepared from galactosyl amine 150 and 5-hexenal was reacted with Danishefsky s diene to give the 2-substituted dehydropiperidinone derivative 196 with high diastereoselectivity. The subsequent addition of propyl cuprate promoted by borontrifluoride etherate furnished the 2,6-c/5 -disubstituted... 

OSiHe, 0.1 equiv. Sc(OTf)3 1.2 equiv. amine 1.2 equiv. aldehyde Mannich imine prepared in situ aldehyde -t- amine [445, 446]... 

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