Ketimine alkylation

The acid-catalyzed reaction of acetophenone with acyclic secondary amines results in the formation of the expected enamine and a rearrangement product. The latter product arises from the transfer of one of the amino N-alkyl groups to the cnamine s carbon to produce a ketimine (53a). 

Iminium salts can be made in a number of ways such as protonation of enamines (7), alkylation of aldimines and ketimines (5,9), cleavage of a covalent bond in a... 

The alkylation of aldimines and ketimines as a method for obtaining iminium salts is now useful only for the preparation of iminium salts not accessible by any of the newer methods. The preparation of and 8 illustrates the conversion of ketimines to iminium salts (9,21). 

The Schiff reaction between chitosan and aldehydes or ketones yields the corresponding aldimines and ketimines, which are converted to N-alkyl derivatives upon hydrogenation with borohydride. Chitosan acetate salt can be converted into chitin upon heating [130]. The following are important examples of modified chitosans that currently have niche markets or prominent places in advanced research. 

Protection of the nitrogen in 4 faced the classical N- versus O-alkylation selectivity issue, which was solved by selection of the solvent system. The original protecting group, pMB, was replaced with 9-anthrylmethyl (ANM), which provided the best enantioselectivity with the newly discovered asymmetric addition to the ketimine. 

Asymmetric addition to ketimine in a reagent controlled manner has seldom been reported, even by 2008. When we investigated the potential for tbis asymmetric addition around 1992, there were no known examples. In 1990, Tomioka et al., reported the first asymmetric addition of alkyl lithium to N-p-methoxyphenyl aldo-imines in the presence ofa chiral (3-amino ether with 40-64% ee [8] (Scheme 1.11). In 1992, Katritzky reported the asymmetric addition of Et2Zn to in situ prepared N-acyl imine in the presence of a chiral (3-amino alcohol with 21-70% ee [15] (Scheme 1.12). In the same year, Soai et al., reported the asymmetric addition of dialkylzinc to diphenylphosphinoyl imines in the presence of chiral (3-amino alcohols with 85-87% ee [16] (Scheme 1.13). These three reports were, to the best of... 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

Scheme 6.57 Rhodium-catalyzed ortho-alkylation of ketimines...

A ketimine can also be alkylated by the same process.140 In situ generation of a ketimine from the aromatic ketone 114 and benzylamine provides an efficient catalytic process with Wilkinson catalyst (Scheme 35). The alkylated aromatic ketone 115 is obtained in good yield. Better reactivity and selectivity are obtained with ketimine... 

Reaction of Various Aldimine and Ketimine Magnesium Bromide Salts with Alkylating Agents in Tetrahydrofuran... 

Ketimines, enamines from, in ketones alkylation, 54, 48 Ketone, aralkyl, selective a-bromination of, 53, 111 Ketone, a,a -dibromodineopen-tyl-, preparation of, 54,... 

Five-coordinate aluminum alkyls are useful as oxirane-polymerization catalysts. Controlled polymerization of lactones102 and lactides103 has been achieved with Schiff base aluminum alkyl complexes. Ketiminate-based five-coordinate aluminum alkyl (OCMeCHCMeNAr)AlEt2 were found to be active catalyst for the ring-opening polymerization of -caprolactone.88 Salen aluminum alkyls have also been found to be active catalysts for the preparation of ethylene carbonate from sc C02 and ethylene oxide.1 4 Their catalytic activity is markedly enhanced in the presence of a Lewis base or a quaternary salt. 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

Formally related reactions are observed when anthracene [210] or arylole-fines [211-213] are reduced in the presence of carboxylic acid derivatives such as anhydrides, esters, amides, or nitriles. Under these conditions, mono- or diacylated compounds are obtained. It is interesting to note that the yield of acylated products largely depends on the counterion of the reduced hydrocarbon species. It is especially high when lithium is used, which is supposed to prevent hydrodimerization of the carboxylic acid by ion-pair formation. In contrast to alkylation, acylation is assumed to prefer an Sn2 mechanism. However, it is not clear if the radical anion or the dianion are the reactive species. The addition of nitriles is usually followed by hydrolysis of the resulting ketimines [211-213]. 

Furthermore, the N-alkylation of 2-aminobenzyl alcohol 114 with ketones 115 in the presence of [IrCl(cod)]2 and KOH gave quinoline derivatives 116 (Equation 10.28) [52]. The reaction may be initiated by the formation of ketimine from 114 and 115, and the ketimine thus formed is oxidized by Ir catalyst and the 114 which serves as a hydrogen acceptor giving the corresponding aldehyde, which is eventually converted into quinoline 116 through intramolecular aldol-type condensation. 

Table 2. sc-Alkylated Cyclic Ketones by Alkylation of Chiral Cyclic Ketimines, Followed by Hydrolysis ... 

Table 3. ot-Alkylated Macrocyclic Ketones by Alkylation of Chiral Macrocyelie Ketimines, Followed by Hydrolysis9... 

Whereas branched ketimines are metalated at the less substituted carbon, metalation and alkylation of unsymmetric imines leads to regioisomers2,4,27. For this reason, only symmetrical ketones and unsymmctrical ketones with one substituent having no a-hydrogens have been applied in alkylation reactions via imines (see Table 4). 

Table 4. oc-Alkylated Acyclic Ketones by Alkylation of Chiral Acyclic Ketimines, Followed by Hydrolysis3... 

Die Reaktion von O-Methyl-benzaldoxim mit Organolithium-Verbindungen, gefolgt von der Reduktion des intermediar gebildeten N-Lithio-ketimins mit Boran-Tetrahydrofuran ergibt sek.-Alkyl-amine2 ... 

A comparison of the dissociation constants shows that 5-amino-3-dialkylamino-l,2,4-thiadiazoles are only slightly more basic than the 3-alkyl-5-amino analogs. The low basicity of these compounds suggests that they exist, like the 5-monoamino analogs (see Section III,D, 1), as enamineB rather than as the more basic tautomeric ketimines.81,87 The prevalence of the 3-enamine form in 3-amino-5-anilino-1,2,4-thiadiazoles is supported by ultraviolet absorption data.122... 

The reductive alkylation reaction consists of a sequence of steps in which the hydrogenation is preceded by chemical processes. For primary amines, one forms the alcoholamine, which could proceed on to the ketimine. Hydrogenation of either the alcoholamine or the ketimine produces the secondary amine product,... 

Since ketimine formation is not possible in the reductive alkylation of secondary amines, this reaction must involve the hydrogenolysis of an alcoholamine. However, if either carbon a to the starting carbonyl has a hydrogen available, the enamine formation is possible. 

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