Formation intramolecular amination

A quinazoline alkaloid skeleton has been synthesized by means of the Rh-catalyzed cyclohydrocarbonylation of diaminoalkenes. The reaction of 2-(A -allylaminomethyl)aniline 55 gave quinazoline 59 in excellent yield through the highly linear-selective hydroformylation of 55 to aldehyde 56, followed by the sequential formations of hemiaminal 57 and iminium ion 58 as intermediates and then the subsequent intramolecular amine addition (Scheme In the same manner, the reaction of A -allyl-2-aminomethylaniline 60 afforded 61 in 96% yield. ... 

Pd-catalysed allylation of amines proceeds smoothly. Allylamine (132) and di- and triallylamines are produced commercially by the Pd-catalysed reaction of ammonia with allyl alcohol using DPPB as a suitable ligand [69]. Allylic alcohols are rather unreactive substrates for 7r-allylpalladium complex formation under usual conditions. The intramolecular amination of 133 afforded the azaspiro ring 134 and the reaction was applied to the synthesis of perhydrohistrionicotoxin (135) [70]. Smooth Pd-catalyzed allylation of the purine base 136 gives 137, which is utilized for the synthesis of nucleosides [71]. 

The scope aromatic C-N bond formation extends beyond simple amine substrates. For example, selected imines, sulfoximines, hydrazines, lactams, azoles, and carbamates give useful products from intermolecular aromatic C-N bond formation. Intramolecular formation of aryl amides has been reported. In addition, allylamine undergoes arylation, providing a readily cleaved amine alternative to the ammonia surrogates benzylamine, t-butylcarbamate, or benzophenone imine. Although it is an amine substrate, the reaction of this reagent is included here because of its special purpose. 

The reaction of trialkylboranes with A-chloro- or A-(benzoyloxy)alkylamines afforded secondary amines via an anisotropic 1,2-shift of the alkyl group from boron atom to nitrogen in the B-N complex intermediate.519-521 Alkylation of A-chlorodimethylamine with primary trialkylboranes to give A,A-dimethylalkylamines was conducted in the presence of galvinoxyl to avoid the formation of alkyl chlorides via free radical process.522,523 A convenient approach to mixed secondary amines is alkylation of alkyl azides with relatively unhindered trialkylboranes in refluxing xylene followed by hydrolysis with water. The reaction smoothly took place at low temperature when trialkylboranes were replaced by alkyl(dichloro)boranes (Equation (108)).524 Intramolecular amination furnished cyclic amines (Equation (109)).400,525-528... 

Zeolites have also been shown to catalyze a variety of acid-promoted cyclizations. Many of these involve the formation of N-heterocycles via intramolecular amination reactions [75-77]. Some examples are shown in Fig. 2.24. 

The formation of 293 was explained considering that Pd triggered initially an intramolecular amination, followed by C-H activation, and then aryl-aryl bond formation. Such a process is dramatically temperature dependent and higher yields were obtained when the reaction was performed at higher temperature (Equation 10) <2003AGE4774, 2004JA14475, 2006CRV4644>. 

Intramolecular palladium-catalyzed cyclization reactions have also been used to synthesize pyrazole derivatives. iV-Aryl-iV-(o-bromobenzyl)hydrazines 494 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2//-indazoles 495 (Equation 101) <20000L519>. Palladium-catalyzed intramolecular C-N bond formation of iV-acetamino-2-(2-bromo)arylindolines 496, followed by hydrolysis and air oxidation in the presence of aluminium oxide, allowed the preparation of indolo[l,2-3]indazoles 498 via intermediate 497 (Scheme 58) <2002TL3577>. 3-Substituted pyrazoles have been prepared from the intramolecular cyclization of A -tosyl-iV-(l-aryl/ vinyl-1-propyn-3-yl)hydrazine and then exposme of the reaction mixture of the cyclization to potassium /i //-butoxide <1997SL959>. iV-Aryl-iV -(o-bromobenzyl)hydrazines 499 or [A -aryl-A -(t>-bromobenzyl)hydrazinato-A ]-triphenyl-phosphonium bromides 501 participated in a palladium-catalyzed intramolecular amination reaction to give 1-phenyl-l//-indazoles 500 (Scheme 59) <2001TL2937>. 

The scope of the lanthanide-mediated, intramolecular amination/cyclization reaction has been determined for the formation of substituted quinolizidines, indolizidines, and pyrrolizidines,1046 as well as tricyclic and tetracyclic aromatic nitrogen heterocycles.1047 The amide derivative OT ro-[ethylene-bis(indenyl)]ytterbium(m) bis(trimethyl-silyl)amide catalyzes the hydroamination of primary olefins in excellent yields.701 A facile intramolecular hydroamination process catalyzed by [(C5H4SiMe3)2Nd(/r-Me)]2 has also been reported. The lanthanide-catalyzed hydroamination enables a rapid access to 10,1 l-dihydro-5//-dibenzo[tf,rf]cyclohepten-5,10-imines (Scheme 283).1048... 

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... 

When formation of a five-, six-, or seven-membered ring is possible intramolecular amination is favored on the metal surface. Examples on the cyclization of terminal amino alcohols over supported Cu catalysts are shown in Scheme 5 [18,19]. Cyclization in methanolic solution can afford the N-methylated heterocyclic compound in one step. Reaction conditions, including the temperature, catalyst support, and the presence or absence of hydrogen, had a strong influence on product composition. 

An intramolecular vinylogous amide photocycloaddition, retro-Mannich fragmentation and final Mannich cyclization cascade provided a useful method for the synthesis of the complex ABCE ring system [91], The preparation of the requisite photosubstrate is outlined in Scheme 28. After cluomatographic separation, the cis alcohol was irradiated and led to the formation of aminals in a 2 1 ratio. Equilibration studies of the Swem oxidation products revealed that exposure of the minor diketone to sodium methoxide in methanol effected conversion to the manzamine-unlike... 

Nitrenium ions and direct electrophilic aromatic amination (cyclic nitrenium ions, formation of N-heterocycles by intramolecular amination, N-aminopyridinium salts) 05ZOR487. 

Zeolites have also known as efficient catalysts for a wide variety of acid-promoted cyclization reactions. Most of them involves the formation of N-heterocycles through the intramolecular amination reaction pathway [48-50]. See examples are shown in Figure 11.13. Pyridines are also being produced by the reaction of ammonia over solid support acid catalyst with various aldehydes [50]. 

Abstract Direct sp C-H bond functionalization is an efficient, straightforward, and powerful method to construct new C-X (X=C, N, F, S) bonds from nonfunctionalized aliphatic motif of organic molecules, which has been used in late-stage modification of complex molecules. In this chapter, the recent developments of silver-mediated direct sp C-H functionalizations are reviewed, categorized by C-C bond formation (C-H insertion), C-N bond formation (intramolecular and intermolecular amination/amidation), C-F bond formation, and C-S bond formation. 

The intramolecular amination of aryl halides could lead to the formation of saturated heterocycles. Depending on the length of the carbon chain, five-, six-, seven- and macroheterocycles can be produced in the presence of transition metal catalysts. Buchwald and co-workers developed a series of palladium-catalyzed catalytic systems with phosphines as the ligand. Alternative systems have been developed during the past years as well, with... 

Formation of 39 can be interpreted by condensation of both reactants to give the imine 41, followed by intramolecular amine addition to the cyano group ( 42) and concluded by tautomerization ( 39). 

Alternatively, the formation of five-, six- and seven-membered rings, such as indoline, quinoline, indolizidine and benzazepine derivatives obtained with [(SIPr)2Ni] by intramolecular amination of appropriated chloro-aromatic amines (Equation (10.7))." ... 

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