Aminopalladation

The Pd—C cr-bond can be prepared from simple, unoxidized alkenes and aromatic compounds by the reaction of Pd(II) compounds. The following are typical examples. The first step of the reaction of a simple alkene with Pd(ll) and a nucleophile X or Y to form 19 is called palladation. Depending on the nucleophile, it is called oxypalladation, aminopalladation, carbopalladation, etc. The subsequent elimination of b-hydrogen produces the nucleophilic substitution product 20. The displacement of Pd with another nucleophile (X) affords the nucleophilic addition product 21 (see Chapter 3, Section 2). As an example, the oxypalladation of 4-pentenol with PdXi to afford furan 22 or 23 is shown. 

Furthermore, treatment of the aminopalladation product with bromine affords aziridines[176]. The aziridine 160 was obtained stereoselectively from methylamine and 1-decene in 43% yield. The aminopalladation of PdCl2 complexes of ethylene, propylene, and 1-butene with diethylamine affords the unstable ir-alkylpalladium complex 161, which is converted into the stable chelated acylpalladium complex 162 by treatment with CO[177],... 

Unlike the intermolecular reaction, the intramolecular aminopalladation proceeds more easily[13,14,166], Methylindole (164) is obtained by the intramolecular exo amination of 2-allylaniline (163). If there is another olefinic bond in the same molecule, the aminopalladation product 165 undergoes intramolecular alkene insertion to give the tricyclic compound 166[178]. 2,2-Dimethyl-l,2-dihydroquinoline (168) is obtained by endo cyclization of 2-(3,3-dimethyiallyl)aniline (167). The oxidative amination proceeds smoothly... 

The intermediate 190 of the intramolecular aminopalladation of an allenic bond with jV-tosylcarbamate undergoes insertion of allylic chloride. Subsequent elimination of PdCl2 occurs to afford the 1,4-diene system 191. The regeneration of Pd(II) species makes the reaction catalytic without using a reoxidant[190]. 

Aminopalladation and subsequent carbonylation are also facile reactions. The carbonylation of substituted 3-hydroxy-4-pentenylamine as a carbamate (254) proceeds smoothly via the aminopalladation product 255 in AcOH to give 256[228). The protection of the amino group of the carbamate as tosyl amide is important in the carbonylation of 257 to give 258[229],... 

The 2-substituted 3-acylindoles 579 are prepared by carbonylative cycliza-tion of the 2-alkynyltrifluoroacetanilides 576 with aryl halides or alkenyl tri-flates. The reaction can be understood by the aminopalladation of the alkyne with the acylpalladium intermediate as shown by 577 to generate 578, followed by reductive elimination to give 579[425]. 

Amines undergo aminopalladation to alkynes. The intramolecular addition of amines to alkynes yields cyclic imines. The 3-alkynylamine 273 was cyclized to the 1-pyrroline 274, and the 5-alkynylamine 275 was converted into the 2,3,4,5-tetrahydropyridine 276[137]. Cyclization of o-(l-hexynyl)aniline (277)... 

The Hegedus indole synthesis involves one of the earlier (formal) examples of olefin hydroamination. An ortho-vinyl or ortho-nllyl aniline derivative 1 is treated with palladium(II) to deliver an intermediate resulting from alkene aminopalladation. Subsequent reduction and/or isomerization steps then provide the indoline or indole unit 2, respectively. 

Scheme 1. Proposed Mechanistic Steps Leading to Olefin Aminopalladation...

An example of an intramolecular palladium-catalyzed oxidation of an allene involving carbonylation was used in the synthesis of pumilotoxin 251 D (equation 32)65. Intramolecular aminopalladation of the allene followed by carbonylation of the palladium-carbon bond and subsequent oxidative cleavage of the acylpalladium intermediate by CuCE afforded pyrrolidine 72 in which the chirality at the carbon at the 2-position was established. 

A Pd(II)-catalyzed sequential cyclization-coupling reaction of allenyl N-tosylcar-bamates and acrolein has been developed (Scheme 16.97) [103]. The proposed mechanism involves intramolecular aminopalladation of an allene, followed by insertion of acrolein and carbon-Pd bond protonolysis. 

Narasaka has utilized a Heck-type intramolecular aminopalladation of the olefinic moiety of r,5-unsaturated ketone 0-pentafluorobenzoyloximes 9 to afford 2,5-disubstituted pyrroles 10 (R = CH3, C02Et) <99CL45>. The use of the O-pentafluorobenzoyl group was found necessary to preclude competing Beckmann rearrangements. 

Intramolecular aminopalladation has been applied to the total synthesis of the complex skeleton of bukittinggine (179). For this reaction. Pd(CF3CO )2 (10 mol%) and benzoquinone (1.1 equiv.) are used. It is important to use freshly recrystallized benzoquinone for successful cyclization. Formation of a 7r-allylpalladium species as an intermediate in this amination reaction has been suggested 182]. The amino group in obromoaniline reacts first with acrylate in the presence of PdCF to give 180, and then intramolecular Heck reaction of the resulting alkene 180 with Pd(0) catalyst affords indolecarboxylate 181[183]. 

The transformation (190 — 191) exemplifies the use of transition metal reagents the reaction probably involves aminopalladation of the C = C bond (77JOC1329). 2,3-Dihydro-4(l//)isoquinolones are obtained by Dieckmann cyclization of 7V-(o-alkoxycarbonylbenzyl)glycine ester derivatives (192 - 193). 

Cyclization of 8-allenylamines is successful also. Synthesis of 2-alkenylpiperidines can be effected with mercury(II) or silver salts, with silver salts giving higher yields (equation 141 and Table 35).268a The significant asymmetric induction found in the cyclization of a chiral allene (78% ee, entry 2) suggests that the low stereoselectivity observed in the synthesis of the 2,6-disubstituted system (entry 3)269 may be a result of starting with a diastereomeric mixture. Aminopalladation/methoxycarbonylation has been effected in moderate yield also (entry 4). 

The usefulness of Pd-catalysed reactions is demonstrated amply in the total synthesis of clavicipitic acid [76]. The first step is intramolecular aminopalladation of the 2-vinyltosylamide 92 with Pd(II) to give the indole 93. Then stepwise Heck reactions of the iodide and bromide of 94 with two different alkenes 95 and 96 in the absence and presence of a phosphine ligand give 97. In the last step of the synthesis, the intramolecular aminopalladation of 97 with a catalytic amount of Pd(II) gives the cyclized product 99. It should be noted that the aminopalladation is a stoichiometric... 

The aminopalladation and subsequent carbonylation proceed smoothly. The aminopalladation of one of the double bonds of allene 129 generates 130, and CO insertion affords the ester 131 [96]. The carbopalladation of the optically active N-vinyl carbamate 132 with malonate afforded 133. Then CO insertion and trapping with vinylstannane produced the ketone 134 with 95% de, which was converted to 135 [97]. 

The intermolecular hydroamination of alkynes, catalysed by the aquapalladium complex [(dppe)Pd(H20)2](0Tf)2, has been reported. The reaction is believed to proceed through the equilibrium between the hydroxopalladium and the amidopalladium complexes, followed by aminopalladation of alkynes.76 Regioselective 1,2-diamination of 1,3-dienes by dialkylureas, catalysed by (MeCN)2PdCl2 in the presence of 1 equiv. of / -benzoquinone, has been developed as a highly efficient method.77... 

Vinyl-substituted 2-oxazolidinones 208 were synthesised by a catalytic <02JOC974> and also asymmetric intramolecular aminopalladation of readily available derivatives of (Z)-2-buten-l,4-diol 207 <02JA12>. 

A one-pot conversion of alkenes to iV-methylaziridines has been achieved by aminopalladation followed by an oxidative woik-up with bromine (Scheme 15). The reaction is stereospecific, as shown by deuteration experiments, but has been little exploited. - 2-Aminopalladium compounds such as (21) are extremely versatile depending on starting compounds and work-up reagents, Aey can be made to yield a wide variety of products (Scheme 16). ... 

Battistuzzi G, Cacchi S, Fabrizi G (2002) The aminopalladation/reductive elimination domino reaction in the construction of functionalized indole rings. Eur J Org Chem 2671-2681... 

The stereochemistry of the aminopalladation reaction with (E)- and (Z)-2-butene was initially established by a three-step conversion of the unstable er-complexes, obtained by the addition of a secondary amine, to 2-butenes11. However, direct proof was obtained by the addition of excess dimethylamine to the same er-complexes the corresponding azapalladacy-clobutanes so formed at low temperature were analyzed by 13C-NMR spectroscopy, which allowed the relative stereochemistry to be assigned12. 

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