Amines aldimines

The hydroamination of alkynes is an efficient way to obtain aldimines with the advantage of avoiding formation of by-products. As shown in Scheme 8.65, the method has been developed into a multicomponent synthesis of a-branched amines. Aldimines 154 are formed using a titanium derivative as catalyst and reacted in situ with an organolithium reagent [141]. 

Alkylative amination. Aldimines RCH=NOBn are susceptible to free radical addition. Thus, a mixture of RCHO, BnONH2, and RT react in the presence of BF3-OEt2 and EtjB to afford RR CHNHOBn. 

There are a variety of reactive diluent compounds available today, including diols/polyols, hindered amines, aldimines, ketimines, and oxazolidines. Amino compounds, in general, are not suitable for use as reactive diluents in 2K systems, unless applied using plural component equipment, because of their very fast reaction with isocyanates to form ureas. 

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... 

Die Stephen-Reduktion von Nitrilen mit Tetrachlor-zinn(ll)-saure fiihrt zu Aldimin-Komplexen bzw. nach Hydrolyse zu Aldehyden (s. Bd. VII/1, S. 299ff. und Lit.1). Die Methode ist fur viele aliphatische Nitrile ungeeignet, da bei ihnen die primar entstehenden Nitriliumsalze ein zweites Molekiil Nitril addieren. In einzelnen Fallen bil-den sich bei der Stephen-Reduktion auch Amine (s. Bd. XI/1, S. 546). 

Another versatile approach, which nicely complements these Mannich-based procedures, incorporates a preformed symmetrical hexahydro-l,3,5-triazine (HHT) intermediate. In this case the phosphorus reagent reacts with HHT as a trimeric form of the normal aldimine species generated in situ between the amine or amino acid and formaldehyde. These HHT reagents can often be puritied and isolated prior to the reaction with phosphites. They are reasonably stable under neutral or slightly basic conditions, but they can readily revert back to the original amine and formaldehyde after heating with aqueous acid (25). Several can be purchased commercially. 

Recent efforts in the development of efficient routes to highly substituted yS-ami-no acids based on asymmetric Mannich reactions with enantiopure sulfmyl imine are worthy of mention. Following the pioneering work of Davis on p-tolu-enesulfmyl imines [116], Ellman and coworkers have recently developed a new and efficient approach to enantiomerically pure N-tert-butanesulfmyl imines and have reported their use as versatile intermediates for the asymmetric synthesis of amines [91]. Addition of titanium enolates to tert-butane sulfmyl aldimines and ketimines 31 proceeds in high yields and diastereoselectivities, thus providing general access to yS -amino acids 32 (Scheme 2.5)... 

In all the above reactions, secondary amines give good yields of butenyl compounds, whereas with primary amines products of high molecular weight, i.e. containing more than 2 butadiene units per mol of amine, are also formed. The latter have been shown to be aldimine derivatives containing three C4 units [203]. 

Reductive coupling of aldimines obtained from aromatic aldehydes and aromatic amines to generate vicinal diamines mediated by indium was carried out in aqueous ethanol (Eq. 11.59)." Small indium rods were used in this study. No side-product was observed due to unimolecular reduction. The presence of NH4CI was found to accelerate the reaction. The reaction fails completely in CH3CN, DMF, or wet DMF. The use of nonaromatic substrates also resulted in the failure of the reaction. 

In general, an aldimine is among the least reactive carbonyl compounds and is by far less reactive than an aldehyde [31-33]. Nevertheless, the Et2Zn-Ni catalytic system is successfully extended to the homoallylation of aldimine. Aldimine prepared in situ from an aldehyde and a primary aromatic amine undergoes the homoallylation smoothly under the essentially identical con-... 

The reaction is also applicable to a wide structural variety of 1,3-dienes, as demonstrated by the reaction of 2-furfural-p-anisidine imine (Table 9). All dienes react with the aldimine regioselectively at the diene termini bearing the highest electron densities and provide bis-homoallyl amines with excellent 1,3-syn diastereoselectivity. No C4-adducts are formed in these reactions. 

The formimidoyl group can be transferred onto either amines, alcohols or CH-active compounds without use of a catalyst, providing amidines or aldimines and enamines, respectively [31... 

Carbonylations of azoderivatives, chloramines, or aldimines are other ways of achieving amination, as shown by the last three examples in Table X. 

The preparation of optically active analogues of the natural amino acids has proven reasonable using the reaction of tris(trimethylsilyl) phosphite with chiral aldimines prepared from optically active amines.225 The asymmetric induction has been observed to be as high as 80%, a significant competitive process compared to the multistep approaches available.226227 An alternative one-step approach involving asymmetric induction upon addition to an aldimine derived from a chiral N-substituted urea provided a product with less desirable optical purity.228... 

Alkenylzirconium reagents generated from alkynes and the Schwartz reagent react with aldimines under mild conditions in the presence of [RhCl(COD)]2 to give homoallylic amine derivatives (Equation (63)).418... 

More recently, Tamaru and co-workers reported nickel-catalyzed reductive coupling of dienes with in situ-generated aldimines from aldehydes and amines (Equation (88)).446,446a The reaction exhibits high regio- and diastereoselectivity. 

Asymmetric reactions have also been developed. The reactions of allyltitaniums with chiral aldimines derived from optically active 1-phenylethylamine afford optically active homoallylic amines with excellent diastereofacial selectivities. Thus, the Cram syn addition products are obtained highly predominantly when using crotyltitanium reagent 33, as exemplified in Scheme 13.30 [61]. 

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>. 

The bismuth- or tantalum-promoted allylation of aldimines 187 (R1 = Ph or PhCH=CHCH2 R2 = Me, Ph or PhCH2) with allyl bromide in the systems Bi/Bu4N+ Br /MeCN or Ta/Bu4N+ Br /MeCN yields the amines 188193. 

Homoallylic amines result from the reaction of aldimines, previously activated by boron trifluoride etherate, with allylic bromides in the presence of chromium(II) chloride, e.g. equation 68194. 

Furthermore, when trimethylsilylacetylene 40 was used as an alkyne in the [IrCl(cod)]2-catalyzed reaction, propargyUc amines (where the alkyne was added to the double bond of imine) were obtained (Equation 10.7) [21, 23]. It is probable that the reaction proceeds through oxidative addition of the terminal C—H bond of alkyne to the Ir complex, followed by the insertion of imine to the resulting Ir-H complex. The crosscoupling reachon of trimethylsilyl (TMS)-acetylene with aldimines took place by [IrCl(cod)]2, leading to the corresponding adducts (Equahon 10.8) [24]. 

The [Ir(cod)2]BARF complex also showed high catalytic activity in the hydrogena-tive coupling of alkyne with aldimines to lead to reductive couphng products, aUyl amines [69]. 

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]. 

The addition of an amine to the carbonyl group of an aldehyde yields—after removal of water—an aldimine (not shown see p. 178). Aldimines are intermediates in amino acid metabolism (see p. 178) and serve to bond aldehydes to amino groups in proteins (see p. 62, for example). The addition of an alcohol to the carbonyl group of an aldehyde yields a hemiacetal (R-O-C(H)OH-R). The cyclic forms of sugars are well-known examples of hemi-... 

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