Hydroamination catalyse

An enantioselective, one-pot sequence of Mannich reaction and hydroamination, catalysed by a combination of the quinine-derived organocatalyst (185) and gold(I)-... 

In 2010, Gong et al. reported a highly enantioselective three-component domino reaction, consisting of an enantioselective aza-Diels-Alder cycloaddition catalysed by a chiral phosphoric acid and a subsequent intramolecular hydroamination catalysed by a gold complex. The domino reaction occurred between aldehydes, an enamide, and 2-(2-propynyl)aniline... 

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... 

Hydroamination of activated alkenes has been reported with complexes 91-93 (Fig. 2.15). For example, 91 catalyses the hydroamination of methacrylonitrile (X = CN in Scheme 2.13) by a range of secondary amines (morpholine, thiomorpholine, piperidine, iV-methylpiperazine or aniline) in good to excellent conversions (67-99%) and anfi-Markovnikov regioselectivity (5 mol%, -80°C or rt, 24-72 h). Low enantioselectivies were induced ee 30-50%) depending on the amine used and the reaction temperature [79]. 

Scheme 2.14 Copper-catalysed intermolecular hydroamination of electron-deficient aryl alkenes...

The proposed reaction mechanism involves intermolecular nucleophilic addition of the amido ligand to the olefin to produce a zwitterionic intermediate, followed by proton transfer to form a new copper amido complex. Reaction with additional amine (presnmably via coordination to Cn) yields the hydroamination prodnct and regenerates the original copper catalyst (Scheme 2.15). In addition to the NHC complexes 94 and 95, copper amido complexes with the chelating diphosphine l,2-bis-(di-tert-bntylphosphino)-ethane also catalyse the reaction [81, 82]. 

Scheme 2.15 Postulated mechanism for the copper-catalysed hydroamination of electron-deficient alkenes...

Finally, intramolecular hydroamination/cyclisation of M-alkenyl ureas was catalysed by the well-defined [AuCl(IPr)] complex (Schane 2.16), in the presence of AgOTf (5 mol%, rt, methanol, 22 h). The cationic Au(lPr)+ is presumably the active species [83]. 

Scheme 2.16 Gold-catalysed intramolecular hydroamination of alkenes...

Anfj-Markovnikov products are only observed. The postulated mechanism for these reactions is analogous to the previously discussed for the copper-catalysed hydroamination (Scheme 2.15) with the coordinated thiolate (rather than the amide) acting as nucleophile [82, 85]. 

In 2003, Livinghouse et al. also reported that chelating bis(thiophosphonic amidates) complexes of lanthanide metals, such as yttrium or neodymium, were able to catalyse intramolecular alkene hydroaminations. These complexes were prepared by attachment of the appropriate ligands to the metals by direct metalation with Ln[N(TMS)2]3- When applied to the cyclisation of 2-amino-5-hexene, these catalysts led to the formation of the corresponding pyrrolidine as a mixture of two diastereomers in almost quantitative yields and diastereos-electivities of up to 88% de (Scheme 10.81). 

Scheme 10.80 Y-catalysed hydroaminations of aminoalkenes with binaphthylamine-derived dithiol ligand.

The synthesis of a series of chiral organophosphine oxide/sulfide-substituted binaphtholate ligands has recently been reported by Marks and Yu and their corresponding lanthanide complexes characterized. These complexes, generated in situ from Ln[N(TMS)2]3, cleanly catalysed enantioselective intramolecular hydroamination/cyclisation of 1-amino-2,2-dimethyl-4-pentene albeit with a low enantioselectivity of 7% ee (Scheme 10.82). 

Scheme 10.81 Y-catalysed hydroaminations of 2-amino-5-hexene with bis(thiopho-sphonic amidates) ligands.

Scheme 10.82 Y-catalysed hydroamination of 1-amino-2,2-dimethyl-4-pentene with bis(thiophosphonic amidates) ligand.

Special dibenzoxazepinones 86, obtained through the general method described in Fig. 16 and containing, as a third additional functionality, a triple bond, have been further cyclized via a palladium-catalysed hydroamination reaction (Fig. 17) [68]. In this way complex polycyclic systems 87 have been assembled in three steps, taking advantage of the three additional functions embedded in the starting component the aryl fluoride, the phenol and the triple bond. 

Several neutral titanium complexes have been shown to catalyse intramolecular hydroamination reactions of alkenes. The corresponding pyrrolidine and piperidine products were formed in up to 97% yields. However, only the geminally disubstituted aminoalkenes were successfully cyclized (Thorpe-Ingold effect).56... 

Iron salts (e.g. FeCls) have been identified as new catalysts for intramolecular hydroamination. A number of olefinic tosylamides underwent the reaction at 80 °C to form the corresponding the N-tosylpyrrolidine derivatives in good yield.63 The same salt can also catalyse Markovnikov addition of electron-rich arenes and heteroarenes to styrenes, giving rise to 1,1-diarylalkanes at 80 °C.64... 

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... 

Intramolecular hydroamination of aminoalkenes CH2=CH(CH2) CH2NH2 and the corresponding alkynes can be catalysed by the calcium /9-diketiminato complex [ HC (C(Me)2N-2,6-Pr2C6H3)2 Ca N(SiMe3)2 (THF)] to produce the corresponding pyrrolidines and piperidines.71... 

The intermolecular hydroamination of alkynes, catalysed by the aquapalladium complex [(dppe)Pd(H20)2](0Tf)2, has been reported. The reaction is believed to proceed through the equilibrium between the hydroxopalladium and the amidopalladium complexes, followed by aminopalladation of alkynes.76 Regioselective 1,2-diamination of 1,3-dienes by dialkylureas, catalysed by (MeCN)2PdCl2 in the presence of 1 equiv. of / -benzoquinone, has been developed as a highly efficient method.77... 

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... 

A detailed mechanistic investigation revealed the steps of the anti-Markovnikov hydroamination of vinylarenes (81) with alkylamines catalysed by (COD)Ru(2-methyl-allyl)2, bis(diphenylphosphino)pentane, and TfOH. Treatment of the catalyst components with an excess of styrene under the catalytic conditions afforded a new... 

Figure 10 13C KIEs for catalysed hydroamination of styrene with aniline in benzene at 80°C.

Access to more simply substituted azepine derivatives 7 and 8 has also been achieved by ruthenium-catalysed intramolecular hydroamination of the aminoalkyne 6 [01JOM149]. 

Figure 9.1 Proposed reaction mechanism for the Zn2+ catalysed hydroamination...

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