Benzaldehydes reaction with azomethine ylides

The "one-pot domino reaction" of A/-benzylaniline with benzaldehyde in refluxing toluene results in a mixture of oxazolidines via a transient azomethine ylide (Scheme 14) <96S367>. The 2-benzoyloxazolidine 69 rearranges spontaneously to the oxazine 70 <96JHC1271>. The ring-closure of derivatives 71 (R = H or Me) of (f )-phenylglycinol to oxazolidin-2-ones... 

Enders et al. (96) recently described the application of the chiral azomethine precursor 61 (Scheme 12.21). The azomethine ylide was formed in situ by heating with different benzaldehydes. The reactions of four different azomethine ylides with A-phenyl maleimide led to the formation of endo-62 and exo-62 in ratios of 2 1 in very high yields. The diastereofacial selectivity was estimated to be >96% de for both products, since no other diastereomers were observed by proton nuclear magnetic resonance ( H NMR) spectroscopy. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

Compound 46 and benzaldehyde are considered to be most likely formed by the ring-opening reaction of aziridine 44, giving an azomethine ylide, followed by hydrolysis. Thermolysis of 32 also affords 44-46, and benzaldehyde in 79%, 100%, 15%, and 16% NMR yield, respectively. This is the first example of aziridine formation from heterocyclobutanes with high coordinate main-group elements. 

The tandem reaction of carbenoids with simple imines to form azomethine ylides which then undergo 1,3-dipolar cycloaddition with various dipolarophiles was first reported in 1972.81 Treatment of phenyldiazomethane with copper bronze in the presence of excess N-benzylidenemethylamine resulted in the isolation of imidazoline 170. Formation of this product was rationalized by carbenoid addition onto the imine nitrogen to give azomethine ylide 169 which then underwent a 1,3-dipolar cycloaddition with another molecule of imine to produce the observed product. Bartnik and Mloston subsequently extended this observation by using other dipolarophiles.82 For example, catalytic decomposition of phenyldiazomethane and A-benzylidenemethylamine in the presence of dimethyl maleate or benzaldehyde gave pyrrolidine 171... 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C=N bonds has recently been studied by the authors group.84 Treatment of 2-(diazoace-tyl)benzaldehyde O-methyl oxime (176) with rhodium(II) octanoate in the presence of dimethyl acetylenedicarboxylate or N-phenylmaleimide produced cycloadducts 178 and 179, respectively. The cycloaddition was also carried out using p-quinone as the dipolarophile. The major product isolated corresponded to cycloadduct 180. The subsequent reaction of this material with excess acetic anhydride in pyridine afforded diacetate 181 in 67% overall yield from 176. The latter compound incorporates the basic dibenzofa, d -cyclohepten-5,10-imine skeleton found in MK-801,85 which is a selective ligand for brain cyclidine (PCP) receptors that has attracted considerable attention as a potent anticonvulsive and neuro-protective agent.86,87... 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C-N double bonds has recently been studied by the author s group [66]. Treatment of 2-(diazoacetyl)benzaldehyde O-methyl oxime (118) with rhodium (II) octanoate in the presence of dimethyl acetylenedicarboxylate or iV-phenylmaleimide produced cycloadducts 120 and... 

The same chiral auxiliary has been used in the cycloaddition of an optically active azomethine ylide to benzaldehyde and to l-nitro-2-(3,4-methylenedioxyphenyl)ethylene Ae ylide was generated in situ by treating (R)-(+)-/V-(l-phenylethyl)-A -cyanomethyl-A -trimethylsilylmethylamine (33) with silver fluoride. Unfortunately, no selectivity was observed in the first case and only a 3 2 preference was expressed in the second. Use of the azomethine ylide derived in the same manner from (/ )-(-)-N-(l-phenyl-2-methoxyethyl)-/V-cyanomethyl-N-trimethylsilylmethylamine (34) displayed a modest, but potentially useful, 4 1 diastereofacial selectivity in its reaction with l-nitro-2-(3,4-methylenedioxyphenyl)ethylene. The precise structure of the major and minor product was not determined (Scheme 25). 

Use of N-substituted 2-aminonitriles in the condensation with carbonyl compounds generates cyano-stabilized azomethine ylides (87BCJ4067). The reaction of benzaldehyde with (methylamino)acetonitrile leading to ylide 84 is an example. 

In the process shown in Eq. (11), N-unsubstituted a-amino esters are employed instead of N-substituted derivatives. The reaction of methyl gly-cinate with carbonyl compounds produces iminium hydroxide intermediates, which are then dehydrated generating N-unsubstituted azomethine ylides 85 (86CL1271 87BCJ4067). Therefore, this method is closely related to the tautomerization route, especially to the acid-catalyzed tautomerization (Section II,C). Benzaldehyde, phenylglyoxal, 2-methylpropanal, and cyclohexanone can be used as carbonyl compounds the corresponding azomethine ylides are trapped with N-methylmaleimide in excellent yields. 

Decarboxylative condensation of N-unsubstituted tx-amino acids with benzaldehyde as an aromatic aldehyde requires somewhat harsher conditions. Benzaldehyde and oc-amino acids are heated under reflux in DMF together with N-phenylmaleimide. The azomethine ylides 108 generated can be captured as mixtures of several stereoisomeric cycloadducts (84CC180). 1-Aminocyclopentane-l-carboxylic acid undergoes a similar reaction with pyridine-3-carbaldehyde in the presence of N-phenylmaleimide to afford a spirocyclic cycloadduct, the maleimide cycloadduct of azomethine ylide 109 (84CC182). 

The three-component reaction of N-benzylidenemethylamine with phe-nyldiazomethane and benzaldehyde proceeds via an azomethine ylide, which is stabilized by 1,3-dipolar addition to an aldehyde, furnishing oxazoli-dine 551 (84T2569). 

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