Intramolecular processes nitrogen nucleophiles

The second set of examples involves the use of thionium ions as electrophiles in inter- and intramolecular processes to obtain a-substituted sulfides (see 24 25, Scheme 20.7T which is the most common type of Pummerer reaction. Applications of this classical Pummerer rearrangement are exemplified in the synthesis of trans-solamin, the synthesis of indolizidine alkaloids, and the synthesis of the CDE ring of erinacine E. The first exanple fScheme 20.10 uses Pummerer chemistry in the generation of a thionium ion, which reacts in an intermolecular tin-mediated ene reaction the second one fScheme 20.11 uses Pummerer chemistry to introduce a nitrogen-containing heterocycle by intramolecular addition to form the coniceine core and the third example fScheme 20.12 is an intramolecular silicon-induced Pummerer reaction with oxygenated nucleophiles applied to the synthesis of a precursor of erinacine. Details of these Pummerer-based strategies are discussed below. 

A survey of the many examples of Lewis acid-promoted Passerini-type reactions, finds that most are characterized by one of four distinct processes a) nucleophilic attack of an additional equivalent(s) of isonitrile to form oligomeric products " (17) b) nitrogen dealkylation to give cyanohydrin-type products (18) c) intramolecular capture of tethered-nucleophiles to form cyclic products (19) and d) intermolecular capture of other weakly-basic nucleophiles such as dissociable counterions of the Lewis acid (20) such as the chloride ion for TiCk. 

Carbanions are some of the most common nucleophiles through which a new C—C bond can be formed. C—C instead of C—O or C—N bond formation can be achieved with oxygen and nitrogen bidentate nucleophiles in intermolecular reactions. However, in the intramolecular processes, C—O and C—N bonds could be formed. Nucleophiles derived from other heteroatoms react to form a new C-hetCToatom bond. 

Early on, Heck and co-workers found that intra- and intermolecular coupling reactions of haloalkenes with alkenes in the presence of secondary amines gave allylamines.t t Apparently, an intermediate 7r-allylpalladium complex is formed by rearranganent of the (7-homoallylpalladium intermediate (see above, B.ii) and in turn attacked by the nitrogen nucleophile. Excellent yields of tertiary aUylamines are obtained in this three-component coupling (Scheme As far as the outcome is concerned, analogous inter-intra- as well as fully intramolecular processes have been estabhshed (Scheme 30 see Table... 

Nitrogen nucleophiles such as amines, and in intramolecular reactions amides and tosylamides, readily add to alkenes complexed to Pd derived from PdCl2 (RCN)2 with reactivity and regiochemi-cal features paralleling those observed for oxygen nucleophiles. Intramolecular nucleophilic attack by heteroatom nucleophiles also occurs in conjunction with other palladium-catalyzed processes presented in the following sections. 

Intramolecular cyclization processes of suitable enol triflates and iodoalkenes bearing proximate oxygen or nitrogen nucleophiles 39 via palladium-catalyzed carbonylative... 

The use of oximes as nucleophiles can be quite perplexing in view of the fact that nitrogen or oxygen may react. Alkylation of hydroxylamines can therefore be a very complex process which is largely dependent on the steric factors associated with the educts. Reproducible and predictable results are obtained in intramolecular reactions between oximes and electrophilic carbon atoms. Amides, halides, nitriles, and ketones have been used as electrophiles, and various heterocycles such as quinazoline N-oxide, benzodiayepines, and isoxazoles have been obtained in excellent yields under appropriate reaction conditions. 

Preparative routes to aziridines and 1-azirines are derived from cycloelimination processes in which one, and sometimes two, bonds are formed directly to the nitrogen atom (Scheme 1). For aziridines these include the two intramolecular cyclization pathways involving either nucleophilic displacement by the amine nitrogen (or nitrenium anion) on the /3-carbon (route a) or nucleophilic displacement by a /3-carbanionic centre on the amine nitrogen... 

The hydrogeh atom bound to the amide nitrogen in 15 is rather acidic and it can be easily removed as a proton in the presence of some competent base. Naturally, such an event would afford a delocalized anion, a nucleophilic species, which could attack the proximal epoxide at position 16 in an intramolecular fashion to give the desired azabicyclo[3.2.1]octanol framework. In the event, when a solution of 15 in benzene is treated with sodium hydride at 100 °C, the processes just outlined do in fact take place and intermediate 14 is obtained after hydrolytic cleavage of the trifluoroacetyl group with potassium hydroxide. The formation of azabi-cyclo[3.2.1]octanol 14 in an overall yield of 43% from enone 16 underscores the efficiency of Overman s route to this heavily functionalized bicycle. 

Several types of intramolecular allylic substitution reactions of carbon, nitrogen, and oxygen nucleophiles catalyzed by metalacyclic iridium phosphoramidite complexes have been reported. Intramolecular allylic substitution is much faster than the competing intermolecular process when conducted in the presence of iridium catalysts. Thus, conditions involving high dilution are not required. Intramolecular... 

Under ordinary conditions, reduction of these imines in dimethylformamide is a two-electron process involving saturation of the carbon-nitrogen double bond [181] because the radical from protonation of the radical-anion is more easily reduced than the starting imine. Immonium salts with two or more phenyl substituents are reduced reversibly in acetonitrile to the radical-zwitterion such as 42. Other immo-niura salts, e.g. 43, are reduced irreversibly to the dimer [182]. Radical-zwitterion intermediates generated from immonium salts exhibit nucleophilic character on carbon. Intramolecular interaction between the reduced immonium function and a... 

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