Imines coupling reactions

Aryl triflates are also good substrates for the benzophenone imine coupling reaction. For example. Singer and Buchwald prepared the desired amino-BlNOL precursor in 87% yield after acidic hydrolysis the amination itself proceeded in 90% NMR yield when DPEphos (19) was used as the supporting ligand, Eq.(132) [107]. 

Figure 5-11 The reversible imine-coupling reaction. The modifications were designed to maintain equivalent numbers of atoms in the linking domain.

An enolate-imine coupling reaction has been used to give the side chain in 59% yield in the key step (272). In this approach the imine 7.4.13 was coupled with the enol 7.4.14 in the presence of MgBr2 to give the adduct 7.4.15 this compound was converted to side chain methyl ester in three steps. 

Scheme 22 Crossover experiment showing the intramolecular nature of the N-Rlm-imine coupling reactions.

In general, imines are too reactive to be used to protect carbonyl groups. In a synthesis of juncusol, however, a bromo- and an iodocyclohexylimine of two identical aromatic aldehydes were coupled by an Ullman coupling reaction modi-fied by Ziegler. The imines were cleaved by acidic hydrolysis (aq. oxalic acid, THF, 20°, 1 h, 95% yield). Imines of aromatic aldehydes have also been prepared... 

Nitriles and oximes are considered together because of common features. Both functions are reduced to primary amines, both undergo coupling reactions to secondary amines, and both are subject to reductive hydrolysis. These similarities arise from a common intermediate, an imine. The imine is... 

The coupling reactions of alkynes and aldehydes catalyzed by iron(III) salts have been discussed above (Scheme 10, routes B and C). The three-component coupling of aldehydes, alkynes, and amines is equivalent to the coupling reaction between alkynes and imines. Wang et al. reported such a three-component coupling catalyzed by FeCls in the absence of any ligand (Scheme 17) [33]. 

The head-to-tail-coupling reactions described above are potentially useful in the design of dynamic combinatorial libraries. Features of these reactions include the rapid and reversible formation of carbon-carbon bonds, multifunctional ene-imine building blocks, and formation of stereo centers upon ene-imine linkage. Support for template-directed synthesis utilizing ene-imine building blocks is the formation of a poly ene-imine species that could recognize 3 -GGA-5 sequences of DNA.48 It is noteworthy that some polyene-imines are helical and could form a triple helix with DNA. 

The discoveries made possible by the use of 13C labels are outlined below. A new ene-imine carbon-carbon bond coupling reaction was discovered that afforded... 

A reaction related to alkene-aldehyde coupling is the alkene-imine coupling. A one-pot cyclization involving such a reaction (Eq. 3.27) proceeds smoothly in a mixture of water-THF. The reaction has been used in the asymmetric synthesis of pipecolic acid derivatives.114... 

Another example of the addition of terminal alkynes to C=N in water is the coupling of alkynes with in-situ-generated A-acylimines (Eq. 4.32) and A-acyliminium ions (Eq. 4.33). In 2002, Li et al. developed a coupling reaction of alkynes with A-acylimines and A-acyliminium ions mediated by Cu(I) in water to generate propargyl amide derivatives.57 Either an activated imine derivative or imininum derivative was proposed as the intermediate, respectively. 

A useful method for the preparation of functionalised thiazoles has been described. Palladium catalysed cross coupling reactions between 4-thiazolyl-5-acetyl triflates 36 and alkynes afforded 4-alkynyl-5-acetylthiazoles 37 in good yields (56-82%). If 37 is then treated with ammonia in methanol, thiazolo[5,4-c]pyridines 39 are formed, probably via the intermediate imine 38 which then undergos a regioselective 6-endo dig cyclisation <99EJOC3117>. 

Titanium-mediated pinacol coupling reactions have been reviewed until 2000.80 81 Since then, various intermole-cular pinacol couplings have been reported with aldehydes, - ketones, a-ketoesters, and imines, as well as asymmetric versions thereof.101-104 Scheme 29 shows one example of an asymmetric pinacol coupling of aromatic aldehydes, promoted and catalyzed by the new chiral titanium complex (A)-75, that has been developed by Riant and co-workers.101 Yields for pinacol products 76 are generally high. Under catalytic conditions, ee is moderate (up to 63%), while stoichiometric conditions allow to obtain up to 91% ee. 

Ytterbium triflate [Yb(OTf)3] combined with TMSG1 or TMSOTf are excellent reagents for the conversion of a-methyl styrene and tosyl-imines into homoallylic amides 32 (Equation (19)) (TMS = trimethylsilyl).29 These conditions produce the first examples of intermolecular imino-ene reactions with less reactive imines. Typically, glyoxalate imines are necessary. A comprehensive examination of the lanthanoid metal triflates was done and the activity was shown to directly correlate with the oxophilicity scale. The first report used preformed imines, and subsequently it was found that a three-component coupling reaction could be effected, bypassing the isolation of the intermediate imine.30 Particularly noteworthy was the successful participation of aliphatic aldehydes to yield homoallylic amines. 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

Cross-Coupling Reactions between Carbonyl Compounds and Imine Derivatives... 

In addition to copper and rhodium catalysts commonly used in the generation of metal carbene complexes, other transition metals have also been explored in the diazo decomposition and subsequent ylide generation.Che and co-workers have recently studied ruthenium porphyrin-catalyzed diazo decomposition and demonstrated a three-component coupling reaction of a-diazo ester with a series of iV-benzylidene imines and alkenes to form functionalized pyrrolidines in excellent diastereoselectivities (Scheme 20). ... 

Recently, Olsson and coworkers have reported a cross-coupling reaction between seven-membered cyclic imidoyl chlorides and alkyl Grignard reagents (Scheme 36). The corresponding substimted imines, which are very difficult to prepare otherwise, are synthesized in good to excellent yields. 

Despite its apparent noble character, gold catalysts have been recently found to be active in many homogeneous and heterogeneous catalytic processes such as oxidation reactions, nucleophilic additions, cross-coupling reactions, and alkene and imine hydrogenations (69—71). Corma and co-workers showed that Au... 

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