Amines, palladium adducts

Chang et al. reported a mild tandem intramolecular hydroamination of yne amines to form an endo-adduct intermediate, which reacts with electron-deficient azides to produce cyclic amidines <06JA12366>. Selected examples of an interesting synthetic route to tropene derivatives 165 via a dual hydroamination strategy is shown below. This one-step reaction makes use of a palladium catalyst and takes place by sequential intermolecular hydroamination of cycloheptatriene with aryl, heteroaryl, and primary alkyl amines to generate intermediate 166, followed by transannular intramolecular hydroamination <06JA8134>. 

Two recent reports have detailed the palladium-catalyzed formation of diaryl-amines to prepare nucleosides of damaged DNA. Sigurdsson et al. reported the formation of a precursor to an interstrand cross-link by the reaction in Eq. (35) [158]. Lakshman reported the reaction of bromonucleosides with amines shown in Eq. (36) as a route to the DNA adducts of carcinogenic aminobiphenyls [159]. In this case, a number of reaction conditions were attempted and those using potassium phosphate and the P,N ligand 13 were effective for the transformation, albeit with high catalyst loads. 

For the case of tri(o-tolyl)phosphine-ligated catalysts, the upper pathway appears to predominate. Oxidative addition occurs first via loss of a ligand from the bisphosphine precursor to form the oxidative adduct, which exists as a dimer bridged through the halogen atoms (equation 33). This dimer is broken up by amine, the coordination of which to palladium renders its proton acidic. Subsequent deprotonation by base leads to the amido complex, which can then reductively eliminate to form the product. When tert-butoxide is used as the base, the rate is limited by formation of and reductive elimination from the amido complex, while for the stronger hexamethyldisilazide, the rate-determining step appears to be oxidative addition. ... 

A step forward in the design of catalysts enabling the N-arylation of amines is to eliminate the activation step (reduction of palladium(II) to palladium(O) prior to oxidative addition). One approach is to use well-defined palladium(O) complexes of (NHC)2Pd or mixed phosphine/NHC,(R3P)Pd(NHC) type [80]. These complexes are efficient catalysts for this transformation at mild temperatures. A second approach is to sidestep two required activation stages in the catalytic cycle and eliminate the need for the preactivation and the oxidative addition processes by using well-defined catalysts that are oxidative addition adducts such as NHC-stabilized palladacycles (Scheme 25) [81]. 

The Pd(II)-catalyzed amination of alkenes with aliphatic amines does not proceed well. However, nnder controlled conditions such as -50 °C, a stoichiometric reaction of simple alkenes with the amines gives the aminopalladation intermediates in which coordination of the amines to Pd(II) is involved. The aminopalladation adducts undergo varions nniqne reactions as shown in Scheme However, these reactions appear to be synthetically less useful because of the use of a stoichiometric amount of palladium. 

Allylic oxidation of cyclohexene and related alkenes can be achieved with catalytic amounts of palladium(II) acetate, Cu(OAc)2, hydroquinone, and O2 as oxidant in AcOH, leading to allylic acetates.Methyl glyoxylate adducts of A-Boc-protected allylic amines cyclize, in the presence of catalytic Pd(OAc)2 and an excess of Cu(OAc)2 in DMSO at 70 °C, to 5-(l-alkenyl)-2-(methoxycarbonyl)oxazolidines (eq 7). ... 

In the synthesis of (lS,8aS)-(- -)-indolizidin-l-ol (88) by Chandrasekhar and coworkeis, the aldehyde 104 derived from D-glucose was converted in situ into the N-benzyHmine, to which was added but-3-enylmagnesium bromide to give the adduct (—)-105 as the sole diastereomer in 72% yield after chromatographic purification (Scheme 10). Protection of the amine as the Cbz carbamate and hydroboration—oxidation of the terminal alkene afforded alcohol (—)-106 which, after debenzylation with ammonium formate and palladium on carbon, needed to be re-protected with Cbz. 

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