Ketene imine

Asymmetric synthesis of 3-amino (3-lactams via Staudinger ketene-imine cycloaddition reaction 98KGS1448. 

CBz-protected benzimidazole gave primarily oxazinone [31], while 3/f-indoles incorporated two equivalents of imine (Eq. 4) [32]. In these cases it appears that the initially formed zwitterionic ketene-imine adduct could not close, and reacted with additional photo activated carbene or substrate. 

The mechanism of the classic ketene-imine reaction to form /J-lactams [17,18] is thought to involve perpendicular attack of the imine nitrogen on the ketene carbonyl carbon from the side of the sterically smaller of the two groups, followed by conrotatory closure of the zwitterionic intermediate (Eq. 6). This... 

Keten-imine werden durch Lithiumalanat in der Regel an der C=N-Doppelbindung an-gegriffen6. 

While the steric explanation is consistent with the observed selectivity, it nonetheless presents an incomplete explanation, as alkylation of 2-methyl-4-cyano-l,3-dioxane 17 also proceeded with very high syn-selectivity [11] (Eq. 5). The selective equatorial alkylation can be rationalized as an anfz-anomeric effect that disfavors axial alkylation of the ketene iminate through filled-shell repulsion. Simple lithiated nitriles are known to exist as ketene iminates, but it would be easy to rationalize the preference for equatorial alkylation by considering the relative stability of hypothetical equatorial and axial alkyllithium reagents, vide infra. Preferential equatorial alkylation was also observed by Beau... 

Dehydration of Amides, Oximes, and Ketene Imines into Nitriles... 

Mermerian AH, Fu GC (2005) Nucleophile-catalyzed asymmetric acylations of silyl ketene imines application to the enantioselective synthesis of verapamil. Angew Chem Int Ed 44 949-952... 

Thermal reactions of N-aryl cyclopropenone imines 268 are differentiated by the nature of the N-aryl substituent. Imines 268 (Ar = phenyl, p-nitro-phenyl) undergo isomerization to N-aryl-2-phenyl-indenone imines 271 when heated in aprotic solvents202. Since in protic solvents, e.g. ethanol, only the iminoester 272 is isolated, evidence seems to be given for the intermediacy of 269 implying carbene and ketene imine functionality, which may either cause electrophilic ring closure with a phenyl group to form 271 or may add to the hydroxylic solvent (272). 

This effect has recently been explained by considering that under microwave irradiation the route involving direct reaction between the acyl chloride and the imine competes efficiently with the ketene-imine reaction pathway, a situation highlighted by theoretical calculations (Scheme 9.69) [42 a],... 

Base-catalyzed addition of glycosyl oxides for anomeric O-activation has been extended meanwhile to trifluoroacetonitrile (see Scheme 9), to dichlor-oacetonitrile, to l-aryl-l,l-dichloroacetonitriles, and to ketene imines (46,51,52). Also 2-(glycosyloxy)-pyridine and -pyrimidine derivatives were readily prepared from the corresponding 2-halo precursors (78). However,... 

These building blocks can be obtained either by the Miller cyclization of (5-hydroxy-ct-amino acids or by the Staudinger reaction7 ([2+2] ketene-imine cycloaddition). The procedure reported here follows the second route and has the advantages of being diastereospecific and to proceed in high yield. For a large scale preparation, the harmful and toxic N-methylhydrazine can be replaced by N,N-dlmethyl-1,3-propanediamine. Further transformations of the key intermediate have been reported elsewhere.7 9... 

Dimerizations can also be observed from the anodic oxidations of ketene imines (Scheme 57) [79] or alkylisothiocyanates (Scheme 58) [80]. 

The rearrangement of E and Z N-crotylamines 245 (R, E or Z=Me) gave the corresponding nitriles 247 with 82 and 68% yield, respectively. Disappointingly, the product was obtained as an inseparable mixture of synlanti diastereomers 247 indicating a low simple diastereoselectivity. Obviously, the intermediate ketene imine fitted neither a chair- nor a boat-like conformation. Hence, a low axis-to-center chirality induction was operative, and E and Z reactants gave a... 

Further information concerning the stereochemical properties of the rearrangement were evaluated by submitting rigid cyclohexane derivatives 254/255 to the reaction conditions. In 1975, House described the allylation of a cyclohexyl cyanide 248 [53]. The initial deprotonation with LDA led to a ketene imine anion 249, which was then treated with allyl bromide. Two potential paths rationalized the outcome an AT-allylation generated the intermediate ketene imines 250/251, which underwent aza-Claisen rearrangement to deliver the nitriles 252/253 alternatively, the direct C-allylation of249 produced the nitriles. 

The cyclic voltammetry of ketene imines of the type 52 (X = H, p-CHj, P-CH3O, p-Br) exhibited two irreversible waves in dichloromethane at a Pt-anode between 0.90-1.25 and 1.63-2.0 V vs Ag/AgCl, respectively. The controlled potential electrolysis at the first wave gave tetracyclic (53), bicyclic (54), and tricyclic (55) products [83] (Scheme 28). 

Scheme 29 describes a plausible mechanism for the formation of the products which fit the observed coulometric (n 0.45 F/mol) and preparative results. The intramolecular cyclization process involves a dimerization between a radical cation 52a and the ketene imine 52 to form the intermediate radical cation 52b which then cyclizes to the radical 52c which can abstract a hydrogen atom leading to 54 or can be further oxidized and transformed through a cyclization and deprotonation reaction to 53 which involves 1 F/mol. However, it seems that the [2 -1- 3]-cycloaddition between the parent compound 52 and the cation 52d giving rise to 55 is the fastest reaction as compared with the intramolecular cyclization of 52d to 53. This can also explain the low consumption of electricity. 

Though the chemical oxidation of aryl-substituted ketene imines with various oxidizing agents [153-156] generally leads to cleavage products, anodic oxida-... 

Density functional and semiempirical AMI molecular orbital calculations have been used to investigate substituent effects on site selectivity in heterocumulene-hetero-diene4 + 2-cycloadditions between ketene imines and acroleins.The new and novel heterocumulenes a, /3-unsaturated thioaldehyde S -oxides (97) behave as both diene... 

Figure 6. MNDO heat of formation hypersurface for singlet vinyl nitrene rearrangements to 2H-azirine, ketene imine and the thermodynamically most favorable isomer, acetonitrile.

Inspection of the MNDO hypersurface shows the assumed vinyl nitrene to lie in a very shallow minimum with the activation barrier for ring closure to 2H-azirine (Figure 1 a ) calculated to be only a few kJ/mole. Whereas the separating hypersurface "ridge" to ketene imine of AA t 70 kj/mole seems insur-... 

The cascade ketene imine [2 + 2] cycloaddition and palladium catalyzed cyclization is a convenient route to furoazepine 98 (X = O) with the fused )S-lactam... 

In an analogous late-stage arylation approach, terminal alkyne 31 was envisioned as a versatile intermediate. Slow addition of 4-pentynoyl chloride to imine 3 and (n-Bu)3N at reflux (efficient condenser, 100°C, 12 h, 1 1 toluene heptane) afforded only trace amounts of 31. Reaction of 4-pentynoyl chloride with triethylamine in methylene chloride under preformed ketene conditions ( 78°C, 1 h), followed by addition of 3 and warming to — 10°C over 4 h, afforded a complex mixture of products. Since high-yield preparation of 31 remained elusive, access to internal alkynyl analogs (type 33) was accomplished by preassembly of the appropriate arylalkynyl acid substrate for the ketene-imine cycloaddition reaction (Scheme 13.9). 

Four-membered ring adducts from 2n + 2n cycloaddition of keten-imines to sulfur dioxide. Isolation of l,2-thiazetidin-3-one 1-oxides. jS-Sultames. Simple method for synthesis of substituted 1,2-thia-zetidin 1,1-dioxide. ... 

Cycloaddition reactions were also carried out using l,2-bis(trifluoromethyl)-fumaronitrile (137,138,191,192). Seven-membered cychc ketene imines (186-188) could actually be isolated in good yields from the reactions with 69,... 

The structure of ketene imine 188 was elucidated by means of a single-crystal X-ray diffraction analysis. Surprisingly, bond lengths of 133 and 120 pm for the cumulated system (C=C=N) hardly deviate from those found in a linear analogue (i.e., diphenylketene p-toluylimine) (193). Apparently, the cumulated bond system of 188 is not linear but rather is bent to an angle of 163.8°. 

In accordance with expectations, the isolable trifluoromethyl substituted ketene imines (186-188) were found to react readily with nucleophilic agents. In the case of 186, the reaction with methanol and aniline led to lactim ether 187a and amidine 187b, respectively (137). 

Reviews including aspects of P-lactam chemistry are ketene-imine cycloaddition reactions <98CHE1222>, radical cyclization processes <98MI169>, combinatorial synthesis <98AJC875>, electrophilic cyclization of unsaturated amides <98T13681> and theoretical studies on the synthesis of P-lactams <98MI245>. 

Monobactams have been investigated as p-lactamase inhibitors <98CHE1308, 98CHE1319>. The ketene-imine route to P-lactams was used to obtain 1,3,4-trisubstituted derivatives with high trans selectivity. The enolate from 4-hydroxy-y-lactone reacted with the imine (Ar CH NAr ) to give 59, vdiich cyclized in the presence of lithium chloride at low temperature to yield 60. The compounds were assayed for cholesterol absorption inhibition and 61 (R = = OH, R = F) was found to be a potent inhibitor of 3-hydroxy-3-... 

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