Olefins intramolecular amination

Hegedus proposed the probable course of the cyclization reaction, which follows a Wacker-type reaction mechanism. Coordination of the olefin to Pd(II) results in precipitate 110, which upon treatment with Et3N undergoes intramolecular amination to afford intermediate 111. As expected, the nitrogen atom attack occurs in a 5-exo-trig fashion to afford 112. Hydride... 

Some intramolecular aminations of olefins have been reported for solenopsin A (Id) and its isomer (Ic) (389-392). The dimer (200) of methyl vinyl ketone was converted to the ketone (202) by a standard procedure. Borohydride reduction of 202, followed by acid-catalyzed cyclization, yielded an exo/endo (60/40)... 

Pd-Catalyzed intramolecular amination of olefins leading to N-heterocycles 91MI40. 

The phenylselenenyl chloride induced intramolecular ring closure of ro-aminoalkenes can be utilized in the synthesis of nitrogen heterocycles. Olefinic primary amines do not cyclize readily in this reaction, while urethane derivatives and secondary amines cyclize according to the following scheme55 56. 

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... 

In 1976, Hegedus et al. described the synthesis of indoles using a Pd-assisted intramolecular amination of olefins, which tolerated a range of functionalities [8a, 114]. For example, the requisite o-allylaniline 119 was prepared in high yield by the reaction of 5-methoxy-carbonyl-2-bromoaniline with n-ally I nickel bromide. Addition of 119 to a suspension of stoichiometric PdCl2(CH3CN)2 in THF produced a yellow precipitate (the putative intermediate 121), which upon treatment with Et, N gave rise to indole 120 and deposited metallic palladium. 

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. ... 

The Hegedus indole synthesis is not only compatible with a wide range of functional groups on the aromatic ring but is also tolerable for the alkyl groups at the 2 or 3 position of the allyl side chain." Other features of this reaction include (a) general accessibility for the intramolecular amination of mono-olefin from primary amines and weakly basic... 

A highly effective Ru-eatalyzed asymmetric intramolecular amination of benzylic and allylic C—H bonds was developed in 2008 by Blakey and coworkers. Ru-Pybox complexes were readily prepared by using Nishiyama s method. Initially, the reaction was tested without any additives. However, the desired product 133 could be produced in only modest yields and ee values (Table 1.10, entries 1-3). Based on the studies by Du Bois, the authors rationalized that a cationic catalyst would be more reactive than the neutral one. Thus, the catalyst prepared from halide abstraction by AgOTf gave improved yields and selectivities (Table 1.10, entries 4-6). Further screening of ligands, solvents, and temperature led to the optimal conditions reaction of sulfamate ester 132 with 5 mol% of C16,110 mol% of PhI(OAc)2, and 230 mol% of MgO in benzene at 4 °C (Table 1.10, entries 7-14). Under these conditions, a series of five- and six-membered-ring products were obtained with up to 71% yield and 92% ee. Notably, the cis-olefin substrate 135 could also participate in the reaction (Scheme 1.50). Under the standard conditions, the... 

In 2006, Stahl reported the activity of 78a and rac-78b in the intramolecular amination of olefins (Equation (9.9)). A variety of substituted heterocycles were generated in fair to very good yields. Interesting features of this reaction are the use of atmospheric O2 as oxidant and the potential for an asymmetric version. 

In a similar vein, the cyclization of aliphatic amino-olefins to nitrogen hetero-cycles has been accomplished by conversion of the amine into the corresponding toluene-/ -sulphonamide, followed by Pd -catalysed intramolecular amination of the olefin."... 

For example (Scheme 13.44), treatment of y-hydroxy olefins with a catalytic amount of PdCl2—(CH3CN)2 and a stoichiometric amount of CUCI2 in methanol under CO leads to intramolecular alkoxylation/carboalkoxylation sequence and formation of substituted tetrahydrofurans 61 [80-83]. Similarly, 4-pentenyl carbamates undergo palladium-catalyzed intramolecular amination/carboalkoxylation to form substituted pyrrolidine derivatives 62 [84,85]. 

Unlike the intermolecular reaction, the intramolecular aminopalladation proceeds more easily[13,14,166], Methylindole (164) is obtained by the intramolecular exo amination of 2-allylaniline (163). If there is another olefinic bond in the same molecule, the aminopalladation product 165 undergoes intramolecular alkene insertion to give the tricyclic compound 166[178]. 2,2-Dimethyl-l,2-dihydroquinoline (168) is obtained by endo cyclization of 2-(3,3-dimethyiallyl)aniline (167). The oxidative amination proceeds smoothly... 

In some reactions intramolecular chalcogen nitrogen interactions may lead to stereochemical control. For example, selenenyl bromides react with C=C double bonds, providing a convenient method of introducing various functional groups. The reaction proceeds readily, but affords a racemic mixture. The modified reagent 15.22 contains a chiral amine in close interaction with the selenium atom. It reacts with olefins affording up to 97% ee of isomer A (Scheme 15.2). ... 

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

The same group recently disclosed a related free radical process, namely an efficient one-pot sequence comprising a homolytic aromatic substitution followed by an ionic Homer-Wadsworth-Emmons olefination, for the production of a small library of a,/3-unsaturated oxindoles (Scheme 6.164) [311]. Suitable TEMPO-derived alkoxy-amine precursors were exposed to microwave irradiation in N,N-dimethylformam-ide for 2 min to generate an oxindole intermediate via a radical reaction pathway (intramolecular homolytic aromatic substitution). After the addition of potassium tert-butoxide base (1.2 equivalents) and a suitable aromatic aldehyde (10-20 equivalents), the mixture was further exposed to microwave irradiation at 180 °C for 6 min to provide the a,jS-unsaturated oxindoles in moderate to high overall yields. A number of related oxindoles were also prepared via the same one-pot radical/ionic pathway (Scheme 6.164). 

Allyl methylcarbonate reacts with norbornene following a ruthenium-catalyzed carbonylative cyclization under carbon monoxide pressure to give cyclopentenone derivatives 12 (Scheme 4).32 Catalyst loading, amine and CO pressure have been optimized to give the cyclopentenone compound in 80% yield and a total control of the stereoselectivity (exo 100%). Aromatic or bidentate amines inhibit the reaction certainly by a too strong interaction with ruthenium. A plausible mechanism is proposed. Stereoselective CM-carboruthenation of norbornene with allyl-ruthenium complex 13 followed by carbon monoxide insertion generates an acylruthenium intermediate 15. Intramolecular carboruthenation and /3-hydride elimination of 16 afford the -olefin 17. Isomerization of the double bond under experimental conditions allows formation of the cyclopentenone derivative 12. 

The reaction was further applied to the synthesis of spiro heterocycles (Scheme 16.4) [8], The oxidative addition of an iodide to a Pd(0) species generates an ArPdl species, into which an internal olefin inserts to form an alkylpalladium complex otherwise difficult to access. Allene participates in the reaction at this stage to provide a jt-allylpalladium complex, which is attacked by the amine intramolecularly to afford the procuct. 

The same group has also reported the use of dithiane functionalized olefinic aldehydes in an intramolecular process. Treatment of 289 with the secondary amine 290 led to the formation of the intermediate ylide 291, which delivered a range of tricyclic products (292) in high material yield as essentially a single stereoisomer after in situ cycloaddition (Scheme 3.95). 

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