Aldimines alkylation

If, however, hydrogen is present in the a-position of the iV-alkyl substituent, 2-alkyl-oxaziridines are easily decomposed by alkali. Base attack on this H atom effects 1,2-elimination at the C—N bond. From (86) and aldimine (87) forms, and a mixture of ammonia and two carbonyl compounds is finally obtained, one of them containing the carbon atom of the original oxaziridine ring, the other originating from the IV-alkyl group (57JA5739). 

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). 

It is not known whether the amine assists the elimination of the nitrogen, but that the iminium salt retains its stereochemistry has been demonstrated (709). When a mixture of 68 and 69of 1 5 ratio is treated with diazomethane, the ratio of 70 71 obtained in 75% yield and determined spectroscopically was still 1 5. The traw-N-isopropyl-N-methylisobutylidinium perchlorate (69) was prepared by alkylation of an aldimine salt with diazomethanc and... 

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. 

Reaction of alkyl halides with metalated aldimines... 

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). 

Triisopropylsilyloxyfurans were effective nucleophiles for the vinylogous Mannich addition to iminium ions that were formed by Rh2(cap)4-catalyzed oxidation of N-alkyl groups by THYDRO <06JA5648>. A stereoselective addition of 2-trimethylsilyloxyfurans to aryl aldehydes-derived aldimines employing a chiral phosphine/Ag complex as catalyst was developed <06AG(I)7230>. The prototypical example is shown below. 

Rapid monoalkylations are achieved in good yield compared with classical methods. Of particular interest is the synthesis of ot-amino acids by alkylation of aldimines with microwave activation. Subsequent acidic hydrolysis of the alkylated imine provides leucine, serine, or phenylalanine in preparatively useful yields within 1-5 min [50], Alkylation of phenylacetonitrile was performed by solid-liquid PTC in 1-3 min under microwave irradiation (Eq. 36 and Tab. 5.14). The nitriles obtained can subsequently be quickly hydrolyzed in a microwave oven to yield the corresponding amides or acids [56]. 

Trivalent phosphorus-halogen reagents have been noted to be of use in obtaining simple Abramov-type products with chloral199 200 and with aldimines.201 Similarly, phosphorus-carboxylate anhydrides have been useful in overcoming the stereochemical difficulties associated with alkyl transfer for obtaining Abramov-type products in a direct manner.202 205... 

Several syntheses of l,3-dioxoperhydropyrrolo[l,2-c]imidazoles have been developed using different strategies. a-Substituted bicyclic proline hydantoins were prepared by alkylation of aldimines 135 of resin-bound amino acids with a,tu-dihaloalkanes and intramolecular displacement of the halide to generate cr-substituted prolines 136 and homologs (Scheme 18). After formation of resin-bound ureas 137 by reaction of these sterically hindered secondary amines with isocyanates, base-catalyzed cyclization/cleavage yielded the desired hydantoin products <2005TL3131>. 

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

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]. 

Reactions of potassium superoxide solubilized in apolar solvents with crown ethers (see Oxidation reactions, p. 356) are also frequently accompanied by elimination reactions. Thus, in DMSO solution, secondary alkyl bromides only yield olefins when treated with the K02 complex of dicyclohexyl-18-crown-6 (Johnson et al., 1978). Scully and Davis (1978) have studied the elimination of HC1 from N-chloramines with 18-crown-6-solubilized K02, KOH, and KOAc in ether solution (27). High yields of aldimines were obtained with K02,... 

As mentioned above, iridium complexes are also active in the formation of amines via the hydrosilylation/protodesUylation of imines. In the presence of 2 equiv. of HSiEts, the cationic complex [lr bis(pyrazol-l-yl)methane (CO)2][BPh4] (C4) catalyzes the reduction of various imines, including N-alkyl and N-aryl imines and both aldimines and ketimmes. Excellent conversions directly to the amine products were achieved rapidly at room temperature in a methanol solution (Scheme 14.7) [53]. 

Furthermore, a highly efficient route to A-tert-butoxycarbonyl (Boc)-protected p-amino acids via the enantioselective addition of silyl ketene acetals to Al-Boc-aldimines catalyzed by thiourea catalyst 4 has been reported (Scheme 12.2)." From a steric and electronic standpoint, the A-Boc imine substrates used in this reaction are fundamentally different from the A-alkyl derivatives used in the Strecker reaction. 

In 2004, Terada and coworkers reported the first asymmetric phosphoric acid-catalyzed Friedel-Crafts alkylation (Scheme 8). Aldimines 11 reacted with commercially available 2-methoxy furan (20) in the presence of BINOL phosphate (/ )-3q (2 mol%, R = S.S-MeSj-C Hj) to provide access to A-Boc-protected 2-furyl amines 21 in high yields (80-96%) and enantioselectivities (86-97% ee) [19]. 

In conjunction with their Friedel-Crafts alkylation, Terada et al. found phosphoric acid (R)-3m (2 mol%, R = 9-anthryl) bearing a bulky 9-anthryl group to mediate the asymmetric Friedel-Crafts-type reaction of a-diazoester 22a with iV-acylated aldimines 26 (Scheme 10). a-Diazo-P-amino esters 27 were obtained in moderate yields (62-89%) and very good enantioselectivities (91-97% ee) [20],... 

Two years after the discovery of the first asymmetric Br0nsted acid-catalyzed Friedel-Crafts alkylation, the You group extended this transformation to the use of indoles as heteroaromatic nucleophiles (Scheme 11). iV-Sulfonylated aldimines 28 are activated with the help of catalytic amounts of BINOL phosphate (5)-3k (10 mol%, R = 1-naphthyl) for the reaction with unprotected indoles 29 to provide 3-indolyl amines 30 in good yields (56-94%) together with excellent enantioselec-tivities (58 to >99% ee) [21], Antilla and coworkers demonstrated that A-benzoyl-protected aldimines can be employed as electrophiles for the addition of iV-benzylated indoles with similar efficiencies [22]. Both protocols tolerate several aryl imines and a variety of substituents at the indole moiety. In addition, one example of the use of an aliphatic imine (56%, 58% ee) was presented. 

Moreover, phosphoric acid (5)-3r (5 mol%, R = SiPhj) bearing a bulky triphe-nylsilyl group turned out to be a suitable catalyst for the asymmetric Friedel-Crafts alkylation of iV-alkyl pyrroles 31 with M-benzoyl-protected aldimines 32 (Scheme 12) [23]. 2-Pyrrolyl amines 33 were obtained in high yields (66-97%) and moderate to high enantioselectivities (42 to >99% ee). 

Scheme 6.127 Typical Fhedel-Crafts adducts resulted from the 121- and 124-catalyzed alkylation of indols with N-protected aldimines. The configurations of the products were not determined.

Table 5. a-Alkylated Aldehydes by Alkylation of Chiral Aldimines, Followed by Hydrolysis2... 

The addition of allylmagnesium halides (2 equiv.) to 1,3-azadienes affords after in situ alkylation dihomoallylamines, which are useful intermediates in the synthesis of azepines or related heterocycles. Activation of the C=N moiety of aldimines by 1-benzotriazolyltrimethylsilane minimizes side reactions. The mechanism involves reversible addition of BtTMS (216) to the imine 217 followed by displacement of the benzotriazolyl group by a Grignard reagent (equation 148). ... 

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