Imines, preparation from

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... 

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]. 

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. 

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 . 

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. 

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. 

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... 

An efficient, versatile protocol for the synthesis of highly enantioenriched a-aminophosphonate has been devised. The addition of lithium diethyl phosphite in THF at room temperature to imines prepared from methyl and methoxymethyl (MOM) ethers of (7 )-(-)-2-phenylglycinol and a wide variety of aldehydes has been explored. The reaction generates predominantly the (R,R) diastereomers whose hydrogenolysis produces a-aminophosphonates in good yields (Scheme 8.67). 

The enantioselective asymmetric allylation of imines has been a synthetic challenge, the initial solutions of which required stoichiometric amounts of chiral allylbor on [87], allylsilane [88], allylzinc [89], or allylindium reagents [90]. Itsuno showed that a chiral B allyloxazaborolidine derived from norephedrine could add to the N trimethylsilyl imine prepared from benzaldehyde in high yield and enantiomeric excess (Scheme 1.22) [91]. Brown later reported that B allyldiisopinocamphenylbor ane is also very effective for the allylation of the same electrophiles, but the addition of a molar amount of water is necessary to obtain high yields [92]. The diastereo and... 

When the N-tosyl imine prepared from ethyl glyoxylate was treated with E-2-butene at 150°C, a 9 1 mixture of adducts 239 and 241 was produced (Scheme 42). It was rationalized that the reaction in fact proceeds via a concerted pericyclic mechanism [86] and formation of the major isomer 239 involves an endo ene transition state 238, while the minor product 241 is formed from the... 

DCT was used for chlorination of an imine prepared from benzaldehyde and benzylamine (69ZC325) (Scheme 59). 

Aliphatic aldehydes reacted with amines and silyl enolates to give the corresponding b-amino esters in high yields. In some reactions of imines, it is known that aliphatic enolizable imines prepared from aliphatic aldehydes gave poor results. 

Racemic and optically active O-protected magnesium imines - prepared from O-protected cyanohydrins - are reduced by borohydride reagents to give preferentially the (i , 6 )-dia-stereomers with a (R, S )I(R, R ) ratio of often >90 106. 

Camphor imines prepared from (+ )-camphor and ( > or (R)-a-phenylethylamine have been reduced with sodium borohydride to yield exclusively the endo- and coco-product, respectively59. An imine prepared from ketopinic acid ethyl ester and benzylamine has been reduced with excess diisobutylaluminum hydride to give the e.w-amino alcohol exclusively61. 

Asymmetric reductions with chiral complex metal hydrides and tricoordinate hydride reagents are rare. Iminium salts25 26 and imines27 have been reduced by chiral complex aluminum hydrides. Optically active 2-substituted Ar-methylpiperidine was obtained by reduction of the corresponding 3,4,5,6-tetrahydropyridinium perchlorate with (—)-menthol lithium aluminum hydride. The optical purity for the -propyl derivative was 12% in favor of the S configuration. Similar reductions of imines prepared from acetophenone and propiophenonc with (-)-mcn-thol-lithium aluminum hydride and ( + )-borneol-lithium aluminum hydride reagents resulted in low (<10%) optical yields in those examples where optical yields could be calculated. 

S-a-phenylethylamine, followed by debenzylation, gives as the unique product the 20a-amine (2a, funtaphyllamine). Similar reduction of the imine prepared from (+)-R-a-phenylethylamine gives essentially the epimeric 20j3-amine (2b). 

Synthesis. - Type C Syntheses (C-C-H-C + S). Imines prepared from aldehydes and t NCR CR R X (X=leaving group,R1,R, R3,R =H, alkyl,Ar) react with S donors such as Na2S to form the corresponding thiazolidines (152)1. ... 

Formation of several pyrazolyl-pyrazolino[60]fullerene adducts (45a-c) from nitrile imines by use of this procedure has been described (Scheme 21.17) [53, 54]. The nitrile imines are generated in situ from the corresponding hydrazone 42a-c and NBS in the presence of EtsN and then reacted with Ceo (1) under the action of microwave irradiation, using a focused microwave oven. The route is simpler than the previously described method, which involved cycloaddition of Qo to nitrile imines prepared from the corresponding N-chlorobenzylidene derivatives [55]. 

The same author [63] reported the synthesis of 1 (3-methylcarbapenem intermediates such as 111 (Scheme 16), employing chiral imines prepared from (S)-methyl 3-hydroxy-2-methylpropionaldehyde and p-anisidine or DAM-NH2. The reaction of diketene 98 with these imines in the presence of imidazole produced a diastereomeric mixture of P-lactams 107 and 108 in a variable ratio. These authors found that the best results in terms of chemical yield and stereoselectivity could be obtained when the [2 + 2] cycloaddition reaction was performed on imines derived from DAM-NH2 toluene as solvent and using 4-methylimidazole instead of imidazole. Under these conditions the P-lactam 108b was obtained in 49% yield and the ratio of isomers 107b/108b was 1 15. 

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