Hydroamination unactivated alkenes

The pincer complexes 89-90 (Fig. 2.14) catalyse the intramolecular hydroamination/ cyclisation of unactivated alkenes, yielding pyrrolidines and piperidines (n = 1,2, respectively). The reactions can be carried out in benzene or water with high... 

Very recently, Genet and Michelet developed a diastereoselective reaction that took place by hydroamination of an unactivated alkene followed by a cydization process under very mild conditions. This 1,6-enyne reaction was compatible with electron-poor aromatic amines, including amines bearing chloride atoms (Equation 8.73), which is very useful for further functionalization of the substituted aniline ring [164]. 

A facile intramolecular hydroamination of unactivated alkenes (58), catalysed by the palladium complex (60), has been reported to take place at room temperature. The formation of hydroamination products (59) rather than oxidative amination products is believed to be due to the use of a tridentate ligand, which effectively inhibits -hydride elimination.78... 

Ph3PAuOTf has been shown to catalyse intra- and inter-molecular hydroamination of unactivated alkenes with sulfonamides in a Markovnikov fashion.115 The same complex catalyses hydroamination of 1,3-dienes with carbamates (e.g. PhCH2OCONH2) and sulfonamides at room temperature.116 An intramolecular version of the hydroamination with the Cbz group (benzyloxycarbonyl) has also been reported. The latter... 

Platinum-catalysed intramolecular hydroamination of unactivated alkenes with secondary alkylamines has been reported. Thus, a number of y- and 5-aminoalkenes reacted in the presence of a catalytic 1 2 mixture of [PtCl2(H2C=CH2)]2 (2.5 mol%) and PPh3 in dioxane at 120 °C for 16 h to form the corresponding pyrrolidine derivatives in moderate to good yields. The reaction displayed excellent functional group compatibility and low moisture sensitivity.92... 

Although Pd-catalyzed intramolecular hydroamination reactions of alkynes have been known for ten years, analogous transformations of unactivated alkenes have only recently been developed [33]. Key to the success of these studies was the use of a cationic palladium complex bearing a pyridine-derived P-N-P pincer ligand (29). For example, treatment of 26 with catalytic amounts of 29, AgB F4, and Cu(OTf)2 led to the formation of pyrrolidine 27 in 88% yield with 4 1 dr (Eq. (1.13)). Detailed mechamstic studies have indicated these transformations proceed via alkene coordination to the metal complex followed by outer-sphere aminopaUadation to provide 28. Protonolysis ofthe metal-carbon bond with acid generated in situ leads to formation of the product with regeneration of the active catalyst. 

Bender and Widenhoefer have reported the room temperature intramolecular hydroamination of unactivated alkenes with N,N -disubstituted ureas catalyzed by a gold(I) N-heterocyclic carbene complex [54], For example, treatment of 2-isopropyl-4-pentenyl urea 78 with a catalytic 1 1 mixture of (IPr)AuCl and AgOTf at room temperature for 22 h led to isolation of pyrroldine 79 in 98% yield as a 5.5 1 mixture of diastereomers (Eq. (11.45)). Gold(I)carbon atoms and was effective for the cycHzation of unsubstituted 4-pentenyl ureas and 5-hexenyl ureas. Conversely, the method did not tolerate substitution at the terminal alkenyl carbon atom. 

Although this chapter is formally not covering recent achievements in rare earth chemistry, it must be mentioned that the first examples of asymmetric intermolecular alkene hydroamination have been reported by Hultzsch and coworkers (Scheme 15.13) [85]. Using a bulky binaphtholate yttrium complex at high temperatures with excess alkene substrate, the first examples of this challenging and highly sought after reaction have been realized with unactivated alkenes. 

Scheme 15.62 Ir-catalyzed hydroamination of unactivated alkene with amides and sulfonamides.

Protected nitrogen substrates in combination with late transition metal catalysts have proven exceptionally useful for addressing the aforementioned substrate scope problems when trying to mediate hydroamination with unactivated alkene substrates. In asymmetric variants of this reaction, early work by Yamamoto showed that protected aminoalkynes could be used as cydohydroamination substrates to yield chiral heterocydes with vinyl substituents [108, 225). Here the chiral chelating phosphine ligand 66 ((J ,J )-RENOPHOS) in combination with a Pd(0) precursor and benzoic acid yielded the desired products in good yield with up to 91% ee (Table 15.26). Unfortunately, to obtain these optimized enantiomeric excesses,... 

When unactivated alkenes were used as substrates, the addition process is referred to as hydroamination [19]. This process is extremely valuable for the preparation of new amines and related compounds and is often catalyzed by transition metal complexes or bases [19]. 

What is a good approach for the Markovnikov hydroamination of simple unactivated alkenes such as 1-hexene ... 

Helgert TR, Hollis TK, Valente EJ. Synthesis of titanium CCC-NHC pincer complexes and catalytic hydroamination of unactivated alkenes. Organometallks. 2012 31 3002-3009. 

Shen X, Buchwald SL. Rhodium-catalyzed asymmetric intramolecular hydroamination of unactivated alkenes. Angew. Chem. Int. Ed. 2010 49(3) 564—567. 

Multiple efficient catalysts were reported for the intramolecular process, while the intermolecular process has been studied predominantly for alkynes. The reactivity of the unsaturated fragment decreases in the order alkyne > allene diene > vinyl arene unactivated alkene with the intermolecular hydroamination of simple alkenes representing the most difficult transformation. The hydroamination of all types of carbon-carbon unsaturated fragments will be covered in this chapter. 

Although alkali metal amides cannot catalyze intermolecular hydroamination of higher unactivated alkenes, allylbenzene derivatives react smoothly via base-catalyzed isomerization into p-methyl styrene derivatives, which are active enough to form hydroamination products (22) [170]. 

A different catalytic cycle for alkene hydroamination is initiated by the oxidative addition of the N-H bond to the metal, followed by insertion of the alkene into the metal-nitrogen bond and reductive elimination to form the amine. The oxidative addition of unactivated N-H bonds to platinum(O) complexes is thermodynamically unfavorable, so the catalytic cycle cannot be completed17, but the successful iridium(I)-catalyzed amination of norbornene with aniline has been reported18. 

A simple Pt-catalyzed protocol has been developed by Widenhoefer and coworkers [230] that uses 2.5 mol% [PtCl2(H2C=CH2)]2 and 5 mol% PPhj for the intramolecular hydroamination of secondary amines (Scheme 15.49). This robust catalyst system can accommodate some functionality (e.g., silyl ethers, hahdes, nitriles, and esters) and unactivated terminal alkenes show good reactivity to give five- and... 

Other Pt(II) catalysts in ionic solvent have been disclosed for alkene hydroamina-tion, including ethylene hydroamination (Section 15.3.2) by Brunet and coworkers [109, 112]. This same catalyst system can promote intermolecular hydroamination of unactivated 1-hexene to give a mixture of products, with the Markovnikov product being formed preferentially (Scheme 15.50) [109]. Even in this specialized reaction medium, elevated temperatures and long reaction times are required with these challenging unactivated substrates. 

Need a good system for the Markovnikov hydroamination of unactivated and 1,1-disubstituted alkenes... 

Common nickel compounds have been used to catalyze the hydroamination of internal activated alkenes (Scheme 3.126) [138]. The reactions were carried out under a high pressure of argon and afforded moderate yields of the enamines. While activated internal alkenes were successfully functionalized using this approach, unactivated substrates such as diphenylacetylene were unreactive and afforded low conversions (-30%). 

ACu-Xantphos system [Cu(0-t-Bu)-Xantphos, 10-15 mol%]-catalyzedsynthesis of pyrrolidine and piperidine derivatives was reported. Some pyrrolidine and piperidine derivatives could be obtained in excellent yields in alcoholic solvents via intramolecular hydroamination of unactivated terminal alkenes bearing an unprotected aminoalkyl substituent. Both primary and secondary amines with... 

Iridium The intermolecular hydroamination of unactivated C=C bonds in ct-olefins (RCH=CH2) and bicycloalkenes (norbornene and norbornadiene) with arylamides (ArCONH2) and sulfonamides has been attained upon catalysis by chiral iridium complexes (PP)IrHCl(NHCOAr)(NH2COAr) [PP = chiral bidentate diphosphine]. Mechanistic studies identified the product of N-H bond oxidative addition and coordination of the amide as the resting state of the catalyst. Rapid, reversible dissociation of the amide precedes reaction with the alkene, but an intramolecular, kinetically significant rearrangement of the species occurs before the reaction with alkene. ... 

Alkali metal-catalyzed hydroaminations of unactivated higher alkenes is significantly less feasible [148, 152],... 

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