Intramolecular Hydroamination of Allenes

Ackermann and Bergman developed a highly reactive titanium precatalyst for the intramolecular hydroamination of allenes 149 [101]. The products 150 and in one... 

Initial studies by Yamamoto et al. developed a highly efficient gold-catalyzed intramolecular hydroamination of allenes under very mild conditions [42]. 

LaLonde RL, Sherry BD, Kang EJ, Dean Toste, F. Gold(I)-catalyzed enantioselective intramolecular hydroamination of allenes. J. Am. Chem. Soc. 2007 129(9) 2452-2453. 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

Reactions of intramolecular hydroamination of alkenes, alkynes, and allenes with the formation of A-heterocycles in the presence of lanthanocene catalysts 02CRV2161. 

We found that the intramolecular hydroamination of the aminoallenes 220 took place in the presence of catalytic amounts of palladium, phosphine, and acetic acid to give the 2-alkenylpyrrolidine and -piperidine 221 in good to high yields (Scheme 71).142 The reaction proceeds through formation of hydri-dopalladium species by the oxidative addition of an N—H bond to palladium(O) and subsequent hydro-palladation of the allene moiety, as mentioned in Scheme 70, type b. 

Neutral group 4 metal complexes appear to possess a relatively broad scope for catalytic hydroaminations. They have been employed for the intramolecular hydroamination of alkynes [2], allenes [3], and alkenes [4] as well as the inter-molecular hydroaminations of alkynes [5] and allenes [6]. Primary aryl- and alkylamines readily react, but secondary amines have posed a greater challenge for this type of transformation with neutral catalysts [7]. For the reactions of the latter, cationic Zr and Ti complexes have been employed in intramolecular cyclizations of aminoalkenes [8]. Very recent work suggests that substrates that are difficult to hydroaminate may favor hydroaminoalkylations instead (Scheme 13.2) [9]. 

Hydroamination of 7i-bonds is one of the most straightforward methods for the construction of C N bonds and, as such, has attracted a lot of attention. NHC- Au catalysts, in line with results obtained in hydration and hydroalkoxylation reactions (vide supra), proved highly efficient in this field and the inter-and intramolecular hydroamination of various alkenes," allenes," and alkynes" were reported with a number of NHC- Au complexes. Among these reports, Widenhoefer published an elegant bis-hydroamination of allenes, leading... 

The iron hydride complex FeH(CO)(NO)(Ph3P)2 has been reported to catalyse selective hydrosilylation of internal alkynes Ar C=CAr with PhSiHj. The corresponding intermediate (Z)-vinylsilanes Ar CH=C(SiH2Ph)Ar thus generated then produce trans-Ar CH=CHAr. With PhMeSi(H)CH=CH2 as the reagent, di-Ar CH=CHAr were obtained. Mechanistic details of this stereodivergent method have been diseussed. Tetrahydropyrans and piperidines (218) were obtained by the Fe -catalysed intramolecular hydroalkoxylation and hydroamination of allenes (217). ... 

A palladium-catalyzed three-component reaction with 2-iodobenzoyl chloride or methyl 2-iodobenzoate, allene and primary aliphatic or aromatic amines to prepare fV-substituted 4-methylene-3,4-dihydro-1 (27/)-isoquinolin-1 -ones was disclosed <02TL2601>. A synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via a Cp2TiMe2-catalyzed, intramolecular hydroamination/cyclization of aminoalkynes was also reported <02TL3715>. Additionally, a palladium-catalyzed one-atom ring expansion of methoxyl allenyl compounds 79 to prepare compounds 80 that can serve as precursors to isoquinolones was reported <02OL455,02SL480>. 

Toste has described the intramolecular enantioselective hydroamination of y- and 6-aUenyl sulfonamides catalyzed by enantiomerically pure bis(gold) phosphine complexes [42]. For example, treatment of the terminally-disubstituted y-allenyl sulfonamide 59 with a catalytic amount of [(R)-3,5-xylyl-binap](AuOPNB)2 (OPNB =p-nitrobenzoate) formed protected pyrrolidine 60 in 88% yield with 98% ee (Eq. (11.34)). Likewise, treatment of 6-allenyl sulfonamide 61 with a catalytic amount of [(JJ)-Cl-MeObiphep](AuOPNB)2 in nitromethane at 50 °C for 24h formed 2-alkenyl piperidine 62 in 70% isolated yield with 98% ee (Eq. (11.35)). Realization of high enantioselectivity in this protocol required employment of both a terminally disubstituted allene and a sulfonamide nucleophile. 

While the focus of this chapter is on hydroamination with amines, impressive recent advances in the hydroamidation and hydrocarbamation of allenes have been disclosed. Espinet showed that acyclic carbenes can be used as ligands for Au(I) to realize intramolecular hydrocarbamation [240], while Widenhoefer has used the commercially available l,3-bis[(2,6-diisopropylphenyl)imidazole-2-ylidine] (IPr) NHC in combination with cationic Au(I) to realize regioselective intermolecular hydroamination of 1,1-disubstituted allenes with benzyl carbamate to access allylamines with quaternary centers adjacent to N. This same catalyst can also accommodate 1,3-disubstituted allenes and even tetrasubstituted allenes (Table 15.19) [241]. Interestingly, these products are in contrast to the preferred products accessed with related Au(I)-phosphine complexes in combination with aniline substrates (Table 15.18) [239]. Hydroureation has been achieved intramolecularly [242, 243] and will be later discussed (Section 15.3.6). 

Several Au-ADC catalysts have been examined in intramolecular hydroamina-tion and hydroalkoxylation reactions of allenes, although no advantages over established systems were uncovered [27c,29a]. Notably, Hong and coworkers showed that highly bulky Au -ADC complex 32 and a comparably hindered acyclic aminooxycarbene complex provide catalytic activities comparable to those attained with equivalently bulky NHC-based catalyst 33 in a fairly challenging intramolecular alkene hydroamination reaction [15b,32]. By contrast, less bulky Au-ADC catalysts were ineffective. 

The development of catalytic methods for the hydroamination of nonactivated alkenes, allenes, and alkynes has received considerable attention in recent years [1]. These highly atom-economical processes allow direct access to industrially and biologically relevant classes of compounds such as amines, enamines, and imines from cheap and readily available starting materials. This has recently led to an ever-increasing range of molecular compounds that have been identified as catalysts for these transformations (Scheme 13.1). Whereas rare-earth catalysts have been found to be mainly active in intramolecular hydroamination, other catalysts - in particular those of the late transition metals - are frequently limited to the addition of weakly basic substrates (aniline, sulfonamides, carboxamides, etc.) to alkenes, alkynes, and allenes. 

In the hydroamination of unsaturated carbon-carbon bonds, gold catalysts play an important role. Intermolecular hydroamination of alkenes [177], 1,3-dienes [204], terminal and internal alkynes [205], and allenes [206] are known to proceed smoothly in the presence of PhsP AufI) or AuCls catalyst. In addition, amino olefins also efficiently undergo intramolecular hydroamination using similar gold catalysts. He and coworkers have developed the catalytic cycloaddition of tosylated amino olefins [207], A representative example is shown in Scheme 18.35. When N-tosylated y-amino olefin (97) is exposed to a mixture of PhsP AuCl and AgOTf (5 mol% each) in toluene at 85 °C, pyrrolidine (98) is obtained in 96% yield. The gold(I)-catalyzed intramolecular hydroamination is applicable to N-alkenyl carbamates [208], N-alkenyl carboxamides [209], and N-alkenyl ureas [210], The use of microwave irradiation results in completing the hydroamination in a much shorter time than that required under thermal reaction conditions [211], The... 

During the course of the author s efforts directed toward the development of useful transformations of allenic compounds [66-77], the author found that the reaction of A -tosylated 2-ethynylaniline 1 with paraformaldehyde 2 and diisopropylamine 3 in dioxane in the presence of copper(l) bromide (Crabbe conditions) [78] afforded a 2-(aminomethyl)indole derivative 7 in 92% yield (Scheme 2) without forming the expected [2-(A -tosylamino)phenyl]allene. This reaction can be rationalized by Mannich-type MCR followed by indole formation through intramolecular hydroamination toward the activated alkyne moiety of a plausible intermediate 6. This is the first example of three-component indole formation without producing stoichiometric amount of salts as byproducts. 

Asymmetric hydroamination has made a significant contribution toward the synthesis of chiral cyclic amines. Intramolecular asymmetric hydroamination of amino alkenes, amino alkynes, and amino allenes has been extensively studied to develop interesting strategies for the synthesis of chiral cyclic amines. 

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