Amidation intramolecular amination

Conversion to Amides. V-Acyloxazolidinones may be converted to the primary amide via the corresponding hydrazide. Alternatively, trimethylaluminum/amine adducts form active transaminationreagents, providing amides of p-hydroxy acy-loxazolidinones through intramolecular amine addition of the aminoaluminum species (eq 65). ... 

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... 

Hydroamination of olefins is also possible with gold catalysts. In this reaction, the attack comes from a nitrogen nucleophile as a carbamate,a urea, an amide,or a sulfonamide. " In the latter case, the reaction can be carried out intermolecularly. While the carbamates, ureas, and amides give only products of intramolecular aminations, the sulfonamides can perform the intermolecular addition. Only the addition of ureas (equation 146) takes place at room temperature, and in the rest of the additions heating is required. The catalysts of choice in all these reactions are cationic gold (I)-species stabilized by phosphines or NHC ligands. The reaction times have been reduced by the use of microwave irradiation. The mechanism of the hydroamination reaction has been studied in detail theoretically. ... 

Further diverse systems have been developed and used in the investigation of intramolecular SET processes. These include styrene/amide-spacer/amine diads, 9-aminoacridine/polyether-spacer/benzoate ester diads, l-(4-cyano-phenyl)-4-(cyanomethylene)piperidine, 7i-donor/polyoxyethylene/Zn(II)por-phyrin/N,N -dimethyl-4,4 -bipyridinium systems, naphthalene/porphyrin/ quinone cyclophanes and their anthracene analogues, pyropheophytin-naphthoquinone diads, rigid donor/bridge/acceptor systems, anilide-substi-... 

Insertion of carbenes into other bonds, particularly O—H and N—H bonds, has found worthwhile application in organic synthesis. Both inter- and intramolecular reactions are possible to give ethers, amines or amides. Intramolecular O—H insertion of the carbene, generated from the diazoketone 105, gave rise to the seven-membered cycUc ether 106 (4.84). In a synthesis of the -lactam antibiotic thienamycin, intramolecular N—H insertion of the carbene, formed from the diazoketone 107, was a key step to give the -lactam 108 (4.85). 

In 2001, Du Bois and co-workers developed the intramolecular amination of diverse C—H bonds, including aliphatic ones, by employing the commercially available Rh-catalyst [Rh2(OAc)4] and oxidant PhI(OAc)2. Inspired by this work, Muller and co-workers realized intra- and intermolecular amidation reactions by in situ formed nitrene species. Employing the chiral dirhodium Rh2(S-NTTL)4 developed by their group, cyclic sulfamidates 104 were synthesized in good yields and stereocontrol with sulfamates 103 and PhI(OAc)2 as the nitrene precursors (Scheme 1.37). Subsequently, they... 

It is known that the oxidative addition of aryl or vinyl halides to a low-valent palladium complex produces an aryl- or vinylpalladium complex, which reacts with carbon monoxide to afford an acylpalladium complex. If alcohol and amine are added to this reaction system, we can obtain ester or amide. " Intramolecular reactions of aryl or... 

All of the above mentioned W,X-acetalizations are based on the well-established ability of phosphoric acids and their derivatives to catalyze asymmetric additions of nucleophiles to imines. Imines are readily activated by Brpnsted acids due to their relatively high basicity, and the intermediate iminium ion possesses strong hydrogen bonding to the chiral anion (Scheme 7). This makes the ion pair reasonably well organized enabling an efficient enantiocontrol. The crucial step in the direct N,N- and 77,0-acetalizations of aldehydes is the intramolecular asymmetric addition to an iminium ion intermediate, which is formed after the condensation of the amide or amine moiety with the aldehyde (Scheme 7). 

A sequential intramolecular amination/N-demethylation/amidation of internal acetylenes (119) has been reported to proceed in the presence of n-Bu4NI as a co-catalyst. The latter additive proved to be the key for the A-demethylation (by 5 2... 

The "zip-reaction (U. Kramer, 1978, 1979) leads to giant macrocycles. Potassium 3- ami-nopropyl)amide = KAPA ( superbase ) in 1,3-diaminopropane is used to deprotonate amines. The amide anions are highly nucleophilic and may, for example, be used to transam-idate carboxylic amides. If N- 39-atnino-4,8,12,16,20,24,28,32,36-nonaazanonatriacontyl)do-decanolactam is treated with KAPA, the amino groups may be deprotonated and react with the macrocyclic lactam. The most probable reaction is the intramolecular formation of the six-membered ring intermediate indicated below. This intermediate opens spontaneously to produce the azalactam with seventeen atoms in the cycle. This reaction is repeated nine times in the presence of excess KAPA, and the 53-membered macrocycle is formed in reasonable yield. 

Carbonylation of halides in the presence of primary and secondary amines at I atm affords amides[351j. The intramolecular carbonylation of an aryl bromide which has amino group affords a lactam and has been used for the synthesis of the isoquinoline alkaloid 498(352], The naturally occurring seven-membered lactam 499 (tomaymycin, neothramycin) is prepared by this method(353]. The a-methylene-d-lactam 500 is formed by the intramolecular carbonylation of 2-bromo-3-alkylamino-l-propene(354]. 

The reverse reaction is an intramolecular acidolysis of amide group by the o-carboxyhc acid to reform anhydride and amine. This unique feature is the result of an ortho neighboring effect. In contrast, the acylation of an amine with ben2oic anhydride is an irreversible reaction under the same reaction conditions. The poly(amic acid) stmcture (8) can be considered as a class of polyamides. Aromatic polyamides that lack ortho carboxylic groups are very... 

S-Substituted thiiranium ions react with secondary amines to give ring-opened products. Nitriles also react with thiiranium ions, probably via an open carbenium ion whose formation is favored by increasing the polarity of the medium by the addition of lithium perchlorate (Scheme 79) (79ACR282). An intramolecular displacement by an amide nitrogen atom on an intermediate thiiranium ion has been invoked (80JA1954). 

It is believed (54IZV47 72JPR353) that in the first stage the intermediate 282 is formed due to the addition of the CH acid to the enamine moiety with subsequent elimination of amine. The enol form of the intermediate 282 undergoes cyclization in two fashions, depending on the nature of substituent X. In the case of the ester (X = OMe) the attack is directed to the cyano group to form substituted 3-methoxycarbonyl-I//-pyridin-2-one (283) or its tautomer (2-hydroxy-3-methoxycarbonylpyridine). With the amide (X = NH2) intramolecular condensation leads to 3-cyano-l//-pyridin-2-one and its hydroxy tautomer (284). 

The alternate schemes that have been developed for achieving removal of the side chain similarly depend on intramolecular Interaction of some derivative of the amine with the amide oxygen to afford some easily hydrolyzed intermediate at an oxidation stage analogous to... 

The method described above may be used for the preparation of a wide variety of butenolides substituted in the arylidene ring with either electron-withdrawing or electron-releasing substituents. y-Lactones such as a-benzylidene-7-phenyl-A 1 -bu-tenolide are isoelectronic with azlactones, but have received much less attention. Like the azlactone ring, the butenolide ring may be opened readily by water, alcohols, or amines to form keto acids, keto esters, or keto amides.7 a,-Benzylidene-7-phenyl-A3,1 -butenolide is smoothly isomerized by aluminum chloride to 4-phenyl-2-naphthoic acid in 65-75% yield via intramolecular alkylation. 

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

The cycloaddition of alkynes and alkenes to nitrile oxides has been used in the synthesis of functionalised azepine systems <96JHC259>, <96T5739>. The concomitantly formed isoxazole (dihydroisoxazole) ring is cleaved by reduction in the usual way. Other routes to 1-benzazepines include intramolecular amidoalkylation <96SC2241> and intramolecular palladium-catalysed aryl amination and aryl amidation <96T7525>. Spiro-substituted 2-benzazepines have been prepared by phenolic oxidation (Scheme 5) <96JOC5857> and the same method has been applied to the synthesis of dibenzazepines <96CC1481>. 

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