Reductive aminations palladium® acetate

N-Allylation of aziridines is often complicated by side reactions. The classical solution to this problem, reductive amination, can also be problematic due to the increased strain energy of the aziridinium intermediate. A way to avoid this difficulty was developed by Yudin and co-workers <2005JA17516, 2004JA5086>. The results obtained showed that NH-aziridines such as 197 or 198 underwent a palladium-catalyzed allylic amination with various allyl acetates affording the desired allylated product 199 and 200 with high levels of regioselectivity and in high isolated yields (Scheme 54). 

This paragraph details carbazole syntheses that involve the formation of new bonds to nitrogen. A direct C-H functionalization/amination of 2-acetaminobiphenyl compounds give carbazoles in one step <05JA14560>. For example, treatment of biphenyl 130 with palladium acetate and copper(II) acetate gave carbazole 131. A short s)mthesis of carbazoles involved the reductive cyclization of 2-nitrobiphenyl compounds mediated by triphenylphosphine... 

Unsymmetrical substituted ureas are likewise synthesized by reductive carbonylation of 4-substituted nitrobenzenes with CO in the presence of an excess of an aliphatic secondary amine using palladium acetate, bipyridyl, and copper tosylate as co-catalyst the best selectivity is obtained by continuously adding the aliphatic amine during the course of the readion (ca. 10 h) [773]. 

The coupling of anilines with arylboronic acids has been described in a process catalysed by palladium acetate without the need for ligands, bases, or salts. The mechanism shown in Scheme 17, where S represents solvent, involves in situ formation of the dia-zonium salt from the aniline, and formation of an arylpalladium alkoxo complex which allows the transmetallation step with arylboronic acids. It has been shown that a free amine may be used as a DG in a palladium-catalysed reaction promoted by soluble silver salts. The latter aid the formation of intermediates, (136), which may undergo cyclopalladation followed by transmetallation with an arylboronic acid and reductive elimination. Related work has shown thatbiaryl-2-amines may react with aryl iodides in the presence of palladium acetate and silver acetate to give mono- or di-arylated species such as (137). 

Another metallization chemistry [9-11] involves the formation of a covalent bond between palladium and platinum ions and the amine groups of DNA bases. A solution of palladium acetate is mixed with a solution of DNA and the palladium ions become associated with DNA by forming covalent bonds with the amine groups of the DNA bases. Subsequent reduction of the palladium ions allows them to form autocatalytic sites for the deposition of a palladium metal coating on the surface of the DNA. Reduction of the palladium bonded to the DNA results in very small metal deposits of palladium. However, there may not be enough metal to form a continuous conducting wire after a single treatment with the palladium... 

The resulting intermediate (—)-107 underwent cyclization to the piperidine (—)-108 after mesylation and base treatment. Acidic hydrolysis of the acetal and reduction of the resulting cycHc hemiacetal with sodium borohydride produced the triol (—)-109, the vicinal diol component of which was cleaved with periodate before reductive amination with hydrogen and palladium on carbon completed the synthesis of (+)-88. 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Complete reduction to the alkane occurs when palladium on carbon (Pd/C) is used as catalyst, but hydrogenation can be stopped at the alkene if the less active Lindlar catalyst is used. The Lindlar catalyst is a finely divided palladium metal that has been precipitated onto a calcium carbonate support and then deactivated by treatment with lead acetate and quinoline, an aromatic amine. The hydrogenation occurs with syn stereochemistry (Section 7.5), giving a cis alkene product. 

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

Buchwald-Hartwig amination of iodobenzene 92 with 2-benzyloxy-4-methyl-aniline 93 affords the diarylamine 94 in high yield (Scheme 32). In this case the Goldberg coupling gives poor yields. Oxidative cyclization of compound 94 using stoichiometric amounts of palladium(II) acetate in acetic acid under reflux leads to the carbazole 95, which by reductive debenzylation provides... 

Reduction of the nitro group to the amine 118 was achieved by hydrogenation over palladium on charcoal under moderate pressure. Again conversion to the final maleimide 119 was achieved by reacting the amine with maleic anhydride followed by cyclodehydration with acetic anhydride and triethylamine at room temperature. 

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. 

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