Palladium catalysis amination

Aside from alkoxycarbonylations, hydroxycarbonylations in the presence of water to yield allenic carboxylic acids [15] (93, Y = OH) and aminocarbonylations in the presence of amines to give the analogous amides [139] (93, Y = NRR ) have also been carried out, respectively (Scheme 7.13). These products of structure 102 can also be obtained if using the propargylamines 101 with R1 = Ph or R3 Z H as starting materials (Scheme 7.15) [140]. Additionally, hydroxycarbonylations, also termed carboxyla-tions, are successful without palladium catalysis by reaction of propargyl halides and carbon monoxide in the presence of nickel(II) cyanide under phase-transfer conditions [141, 142]. 

Table 3. Catalysis results for the Barbier reaction of benzaldehyde and allyl bromide in presence of homogeneous palladium catalyst (entry 1) and those prepared by complexing palladium to amine functionalized mesoporous silica (entry 2-4) [74]...

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

A few synthetic applications of palladium catalysis appeared this year. The palladium-catalyzed cyclization of amino allenes 58 occurs with coupling of aryl iodides or vinyl triflates at the 3-position <990L717, 99SL324>. The cyclization can also proceed by the exo-trig pathway, but under suitable reaction conditions the piperidine 59 is prepared selectively. The intramolecular cyclization of amines onto N-allylbenzotriazoles similarly affords piperidines <99JOC6066>. 

The triflate 125 is formed from the hydroxy precursor (Equation 131) and undergoes a variety of nucleophilic substitution processes <2006TL4437>, including Suzuki and Stille couplings (Equations 132 and 133, respectively). Amination of 125 with aliphatic amines occurs under thermal conditions, using either conventional or microwave heating (Equation 134), but the reactions of 125 with less reactive amines require palladium catalysis (Equation 135). 

A highly regioselective amination of 6-aryl-2,4-dichloropyrimidines has been developed using palladium catalysis. The reaction which works well with secondary aliphatic amines and with anilines gives the 4-substituted products.46 Palladium catalysis has also been used in the regioselective coupling of 2,3-dibromopyridine with a series... 

The EMCR has been extended from obtaining enantiomerically pure alcohols to obtaining such amines. Prochiral ketoximes were transformed to optically active amine acetates in a coupled CALB/palladium catalysis in the presence of an acyl donor at 1 atm hydrogen (Figure 18.15) (Choi, 2001). 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

Most recently, Wagaw, Yang, and Buchwald published a full account of the synthesis of indoles using the palladium-catalyzed amination process [185]. From the standpoint of catalysis, new results included improved turnover numbers and rates when Xantphos was used as ligand. Moreover, this ligand allowed diarylation of the hydrazone, including a one-pot sequential diarylation to provide mixed diaryl hydrazones. A procedure for the alkylation of N-aryl hydrazones was also reported. These procedures allow the formation of N-aryl and N-alkyl indoles after subjecting the products to Fischer conditions for indole synthesis. 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

For amination with aliphatic amines, copper catalysis is normally superior to palladium catalysis, e.g., <2006T4435>. Thus, reactions of primary or secondary amines, including pyrrolidine and morpholine, with 5-bromopyrimidine using copper bromide and a phosphite ligand give 5-aminopyrimidines in excellent yields (Scheme 116) <2006T4435, 2005OL3965>. 

During (he last few years, a novel Pd(O)-catalyzed method for C-N bond formation from amines and aryl halides has emerged largely due to contributions from the Buchwald and Hartwig groups [120, 121]. In one application, an intramolecular C-N bond linkage was realized using classic palladium catalysis condition in Buchwald s synthesis of tetrahydropyrroloquinoline... 

Intramolecular displacement of an orf/to-halogen can be achieved at high temperature or with copper(I)-catalysis. " Palladium-catalysed aminations of halide can be used to form either the N-C-2 or N-C-7a links, or both, for example in the double displacement shown below. ... 

It has been shown that hydroxide bridged dimeric palladium complexes can form and impede catalysis, see Hartwig, J.F. Palladium-catalyzed amination of aryl halides mechanism and rational catalyst design. Synlett 1997, 4, 329-340. 

We have already seen that p-bromophenol can be joined to an amine with palladium catalysis, so it should be easy to join it to piperazine. However, there is a potential problem of selectivity we want to add this benzene ring just once, and the way to do this is to protect one nitrogen atom by reductive amination with benzaldehyde. The remaining NH group can then be coupled to the aromatic ring and the benzyl group removed by hydrogenation. 

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