Ketenes with amines

Photocyclization of a,/3-unsaturated amides (152) also gives /3-lactams. This proceeds by cleavage of the intermediate biradical (153) to give ketene and imine which recombine. A small amount of amide (154) results from reaction of the ketene with amine that is produced by hydrolysis of the imine. This type of photodealkylation detracts from the generality of the process (79JCS(P1)263, 77T485). 

Photocyclization of NA -bisbenzylmethacrylamide (12) proceeds by cleavage of the biradical (13) to give dimethylketen and the imine, which recombine. A small amount of (14) results from the reaction of the keten with amine that is produced by hydrolysis of the imine. With di-isopropylmethacrylamide this photodealkylation is the major pathway, the alkylimine being less efficient in [2 + 2] addition to the keten.An unprecedented type II conversion is observed in the selective formation of jS-lactams in the solid-state irradiation of HN-dialkyl-a-oxoamides (15). In solution, other processes complicate the reaction. 

Photochemical Wolff rearrangement of diazoacetylpyrazoline forms ketene 76 in acetonitrile solution, identified by the ketenyl IR absorption, together with the ylide 77 (Eqn (4.40)). Similar intermediates are formed from diazoacetylpyrinfrdine, and the reactions of these ketenes with amines and kinetic studies of their hydration reactivity have been... 

The previous sections have dealt with stable C=N-I- functionality in aromatic rings as simple salts. Another class of iminium salt reactions can be found where the iminium salt is only an intermediate. The purpose of this section is to point out these reactions even though they do not show any striking differences in their reactivity from stable iminium salts. Such intermediates arise from a-chloroamines (133-135), isomerization of oxazolidines (136), reduction of a-aminoketones by the Clemmensen method (137-139), reductive alkylation by the Leuckart-Wallach (140-141) or Clarke-Eschweiler reaction (142), mercuric acetate oxidation of amines (46,93), and in reactions such as ketene with enamines (143). 

Figure 5.29 pNPDP reacts with amine-containing compounds by its p-nitrophenyl ester group to form amide bonds. After photoactivation of the diazo derivative with UV light, a Wolff rearrangement occurs to a highly reactive ketene intermediate. This group can couple to nucleophiles such as amines. 

Exercise 17-38 Write reasonable mechanisms for the reaction of ketene with alcohols and amines. Would you expect these reactions to be facilitated by acids, or by bases ... 

Ozonolysis of ketene dimer gives a very unstable compound that can be observed only at low temperatures (-78 °C or below). It has two carbonyl bands in the IR and reacts with amines to give amides, so it looks like an anhydride (Chapter 12). Can it be the previously unknown cyclic anhydride of malonic acid ... 

Cyclic ketene acetals can also react with amines to give 1,1-enediamines with elimination of ethylene glycol76. Treatment of 2-[(methoxycarbonyl)cyanomethylene]-1,3-dioxolane (38) with 1,3-diaminopropane or with 4,5-dimethyl-1,2-phenylenediamine gives the hexahydropyrimidine and the benzimidazoline derivatives 39 and 40, respectively (equation 11). Similarly to the reaction of ketene dithioacetals with amines, the reaction between ketene acetals and amines proceeds via monoamino-substituted intermediates and ketene 7V,Oacetals can be isolated when one molar amine is used72. 

Ketene N, O-acetals are converted to 1,1-enediamines when reacted with amines. For example, compound 45 has been prepared by substitution of the methoxy with amine (equation 16)79. Symmetric 1,1-enediamines are obtained when both the alkoxy and the amino substituents are displaced by the amine employed81. In this way, the reaction between ketene N, O-acetals 50 and piperidine leads to 1,1-dipipefidinoethylene (35) (equation 17)81. Alternatively, 35 can be prepared from the reaction of piperidine with triethyl orthoacetate82,83 or with ethoxyacetylene84, reactions which probably proceed via a ketene TV, 0-acetal intermediate. 

Enantiopure p-lactones have been obtained from the reaction of acid chlorides or ketene with aldehydes in the presence of optically active tertiary amines. The reaction of ketene with chloral has been studied in considerable detail (Scheme 2). In the presence of 2 mol % of quinidine at -SO C die p-lac-tone is formed in virtually quantitative chemical and optical yield By proper choice of the catalyst, either enantiomer of the -lactone can be obtained. The transition state picture (4) has been propos for the ketene-chloral addition in the presence of quinidine. Hydrolysis converts the -lactone to malic acid with inversion of configuration (Scheme 2). ... 

The preparation of p-lactams by the direct combination of isolated ketenes with imines is severely limited by the instability of monosubstituted and heterosubstituted ketenes, which show a great tendency to polymerize." The discovery that ketenes can be readily generated by the reaction of an acid chloride with tertiary amines offers a practical solution to this problem. ... 

A significant advance in the study of cyclopropanones resulted from studies by the Turro and the de Boer groups on the formation of cyclopropanones in solution by the reaction of ketenes with diazoalkanes. These investigators found that it is possible to store the parent ketone only for short periods at low temperature because of its unusual reactivity and propensity for polymerization. Subsequent work has shown that cyclopropanone seems to show chemical behavior similar to that of ketene. Thus, it is attacked by nucleophilic species such as water, alcohol and amines and reacts rapidly with itself to form... 

By electrolysis of 2-bromoamides in DMF the aminal esters (492 Scheme 89) are accessible. In the reaction of benzoylphenyl ketene with the isoquinolinedione (493) the heterocyclic aminal ester (494) is formed. Another heterocyclic aminal ester (496) was obtained from a hydrazinoyl chloride and a benzoxazine derivative (495). ... 

The reaction of ketene with primary amines proceeds rapidly and in high yield. 

Amide enolates mirror ester enolates in their amination reactions. Secondary amides can be used by employing two equivalents of the base, but yields in the only example found in the literature are low to fair.212 Ketene aminals react with azodicarboxylic esters at room temperature, but yields are low (Eq. 125).251 Eq. 126 shows the application of the copper-catalyzed enantioselective addition of mixed ketene acetal/aminals to azodicarboxylic esters previously described for silyl enol ethers in Eq. 94.252 Increasing bulk of the R substituent in the substrate causes partial or complete amination on the pyrrole, as evidenced by the yields of products 60 and 61 as R is varied. 

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