Palladium nitrogen-containing heterocycles

A-Amine oxides can be reduced (deoxygenated) to tertiary amines. Such a reaction is very desirable, especially in aromatic nitrogen-containing heterocycles where conversion to amine oxides makes possible electrophilic substitution of the aromatic rings in different positions than it occurs in the parent heterocyclic compounds. The reduction is very easy and is accomplished by catalytic hydrogenation over palladium [736, 737], by borane [738], by iron in... 

Cacchi, S., Fabrizi, G., Parisi, L. M. Nitrogen-containing heterocycles via palladium-catalyzed reaction of alkynes with organic halides or triflates. Heterocycles 2002, 58, 667-682. 

The enantio- and diastereoselective synthesis of the nitrogen-containing heterocyclic compounds 612 was achieved by a one-pot reaction via the ruthenium-catalyzed enyne coupling of 608 with 609 followed by the palladium-catalyzed asymmetric C—N bond formation (Scheme 186).264a The enyne coupling reaction proceeds through formation of the ruthenacycle 611 followed by -elimination—reductive elimination. 

Stille cross-couplings of heteroaryl chlorides, mainly nitrogen-containing heterocycles, have often employed traditional triarylphosphine-based palladium catalysts. In one of the earliest examples, Yamanaka showed that 2- and 4-chloro-3-nitro-pyridines react with (Z)-l-ethoxy-2-tributylstannylethylene in good yield, with the products possibly being converted to IH-pyrrolopyridines (Equation 2.39) [71]. 

In 1993, Corriu et al. studied the synthesis of nitrogen-containing heterocycles from (Z)-3-(tribulylstannyl)allylamine, which was prepared by the reaction of Af-(trimethylsilyl)allylamine with 2 mol of ra-butyllithium followed by treatment with chlorotributyltin and subsequent hydrolysis. The unprotected (Z)-3-(tributylstannyl)allylamine underwent a palladium-catalyzed cross-coupling reaction with aromatic bromides affording a stereospecific preparation of substituted allylic amines with Z configuration of the carbon-carbon double bond. The reactions of o/t/zo-functionalized aryl bromides offer a one-step preparation of 7-membered nitrogen heterocycles in high yields (Scheme 4.18). 

Nack WA, Chen G (2015) Syntheses of nitrogen-containing heterocycles via palladium-catalyzed intramolecular dehydrogenative C-H amination. Synlett 26(18) 2505-2511... 

Poll reported a similar method to synthesize nitrogen-containing heterocycles via it-allyl-palladium intermediate [11]. It was worth noting that when the reaction is conducted in acetic acid rather than in methylene dichloride or terahydro-furan, a strong accelerating effect occurs in direct intramolecular allylic C(sp )-H cyclization (Scheme 2.6). Stoichiometric tests and computational Density Functional Theory analysis of the palladium reoxidation step provided an overview of the structural and energetic role of acetic acid in increasing the efficacy of the entire catalytic cycle (Scheme 2.6). 

In 2012, Chen and coworkers developed the palladium-catalyzed intramolecular amination of C(sp )-H at y and 5 positions to synthesize a series of nitrogen-containing heterocycles [15], including azetidine (Scheme 2.11), pyrrolidines, and indolines. With the optimal conditions, using catalytic Pd(OAc)2, an oxidant (PhI(OAC)2, 2.5 equiv.) and an acid additive (AcOH) in toluene at llO C, Chen tested them on other picolinamide substrates bearing primary y-C(sp )-H bonds surprisingly, the seemingly unfavorable four-membered azetidine was obtained as the major product. It is possible that a Pd(IV) intermediate was formed via PhI(OAC)2 oxidation of the palladacycle intermediate because the subsequent C-N and C-O reductive elimination pathways would lead to the formation of the cyclized and acetoxylated product. It was also noteworthy that no P H elimination product was detected under the aforementioned reaction conditions. 

In this chapter, we have presented some examples for the efficient synthesis of nitrogen-containing heterocycles. In the last two decades, many novel synthetic routes have been developed to prepare nitrogen-containing heterocycles via the chemical transformation of palladium-catalyzed C-H activation. Many of these... 

Metallic palladium, which is formed during the catalytic reactions, can be reactivated by contact with heterocyclic aromatic nitrogen containing ligands, halide derivatives of elements of the III- J groups or Py.HCl and oxidizing agents 042,14. ... 

Phenyl ethylenesulfonate, 241 Tin(IV) chloride, 300 Containing one sulfur 2,4-Bis(4-me thoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide, 38 Titanium(IV) chloride-Zinc, 310 Other five-membered heterocycles Carbon dioxide, 65 Methanesulfonyl chloride, 176 Six-membered rings Containing one nitrogen—piperidines Dichlorotris(triphenylphosphine)-ruthenium(II), 107 Mercury(II) trifluoroacetate, 175 Tetrakis(triphenylphosphine)-palladium(O), 289... 

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