Aminoalkynes intramolecular hydroamination

Access to more simply substituted azepine derivatives 116 and 117 has also been realized by ruthenium-catalyzed intramolecular hydroamination of the aminoalkyne 115 (Equation 16) <2001JOM(622)149>. The isolated yield of 116 was 21% and of 117 was only 13%. 

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]. 

Intramolecular addition of amine N-H bonds to carbon-carbon multiple bonds would afford nitrogen heterocycles. To realize catalytic cyclization of a,co-aminoalkenes or aminoalkynes, various catalytic systems have been developed especially with early transition metals such as titanium, zirconium, lanthanide metals, and actinide metals [ 12], Late-transition-metal catalysis based on Ni, Pd, and Rh has also proved to be efficient [ 12], Recently, the ruthenium-catalyzed intramolecular hydroamination of aminoalkynes 15 was reported to afford 5-7-membered ring products 16 in various yields (Eq. 6) [13]. Among... 

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>. 

The complexes were used in catalytic intramolecular hydroamination reactions resulting in the intramolecular cyclisation of aminoalkynes [298,299]. 

Type 4 metallocene complexes catalyze the regioselective mtermolecular addition of primary amines to acetylenic, olefinic, and diene substrates at rates which are = 1/1000 those of the most rapid intramolecular analogues [165]. Variants such as the intramolecular hydroamination/cyclization of aminoallenes [166] and the intra- and intermolecular tandem C-N and C-C bond-forming processes of aminodialkenes, aminodialkynes, aminoallenynes, and aminoalkynes [167] were applied as new regio- and stereoselective approaches to naturally occurring alkaloids. For example, bicyclic pyrrolizidine intermediate E... 

Rare-earth metal complexes have proven to be very efficient catalysts for intramolecular hydroamination reactions involving aminoalkenes, aminoalkynes, aminoallenes, and conjugated aminodienes [88, 97]. They are significantly less efficient in intermolecular hydroamination reactions and only a limited number of examples are known [98-102]. The difficulties in intermolecular hydroamination reactions originate primarily from inefficient competition between strongly binding amines and weakly binding alkenes for vacant coordination sites at the catalytically active metal center. 

Equation 11.9. Palladium catalyzed asymmetric intramolecular hydroamination of aminoalkynes [115]. 

In the first total synthesis of pseudodistomin D 261, the 1,2-diamine 262 of known absolute configuration was prepared and cychzed to 263 by sequential hydroamination and in situ imiue reduction. The absence of any pyrrolidine product formation was rationalized mechanistically (Scheme 79) <05OL823>. A high-yield intramolecular hydroamination protocol has been developed for sulfonyl-protected primary aminoalkynes and application to piperidine synthesis... 

Scheme 11 Proposed mechanism for the organoactinide-catalyzed intramolecular hydroamination/cyclization of terminal and disubstituted aminoalkenes, aminoalkynes, aminoallenes, and aminodienes...

Some of the most active catalysts for the hydroamination of alkynes are based on lanthanides and actinides. The turnover frequencies for the additions are higher than those for lanthanide-catalyzed additions to alkenes by one or two orders of magnitude. Thus, intermolecular addition occurs with acceptable rates. Examples of both intermolecular and intramolecular reactions have been reported (Equations 16.87 and 16.88). Tandem processes initiated by hydroamination have also been reported. As shown in Equation 16.89, intramolecular hydroamination of an alk5me, followed by cyclization with the remaining olefin, generates a pyrrolizidine skeleton. Hydroaminations of aminoalkynes have also been conducted with the metallocenes of the actinides uranium and thorium. - These hydroaminations catalyzed by lanthanide and actinide complexes occur by insertion of the alkyne into a metal-amido intermediate. 

Tsuji-Trost reaction is used to prepare the requisite secondary aminoalkyne for intramolecular hydroamination. Finally, olefin isomerization results in the preparation of functionalized 1,2,5-pyrroles [327]. 

Qrganolanthanides such as metallocene or halfmetallocene andnomnetallocene lanthanide amides, alkylides, and hydrides are highly efficient catalysts for the intramolecular hydroamination/cyclization of a wide range of substrates such as aminoalkenes (Scheme 2), aminoalkynes, aminoal-lenes, and aminodienes. ... 

Enantiomerically pure Norphos derivatives were synthesized and used as chiral bisphosphine ligands for the catalyst system Pd(dba)3 CHCI3/ PhC02H in the intramolecular hydroamination of aminoalkynes. The synthetic approach to the racemic bis(phosphine oxide) precursor of Methyl Norphos is shown in Scheme 7. ... 

The tetrakisamido titanium complex is also efficient in catalysis of intramolecular hydroamination of aminoalkynes and aminoallenes to obtain cycloimines [318]... 

The hydroamination of alkenes and alkynes provides a highly atom-economical method for the preparation of substituted amines and imines. Despite substantial efforts and recent progress, the development of a generally applicable functional group-tolerant catalyst for this reaction remains a challenge, and intense research continues in this field. An interesting example has been reported by means of Rh combined with a bidentate NHC ligand [eqn (8.14)]. Complex 32 was found to catalyse the intramolecular hydroamination of aminoalkynes. However, the turnover rates remained modest with values up to 50 h ... 

The intramolecular hydroamination reaction of aminoalkenes and other substrates involves two key steps in the catalytic cycle. Although the insertion step is generally perceived as the rate-determining step of the process, this may not be true for aU substrate classes. The hydroamination/cyclization of aminoalkenes differs significantly from reactions involving aminoalkynes, aminoaUenes, and conjugated aminodienes from a thermodynamic point of view. The alkene insertion step of the... 

Cationic palladium(II) complexes are homogeneous catalysts for both intramolecular and inter-molecular hydroamination reactions.267 Palladium species immobilized on silica can be prepared by the simple addition of alkyl- or hydroxopalladium(II) complexes to partially dehydroxylated silica. The silica-bound species are more stable than their molecular precursors and are efficient catalysts for the cyclization of aminoalkynes.268... 

Selected examples of intramolecular aminoalkyne hydroamination catalyzed by rare-earth metal complexes (see Figs.8, 16, and 18) are shown in Schemed and Tables. Formation of five-, six-, and seven-membered cyclic imines has been achieved in excellent yields. 

Intermolecular hydroamination of alkynes, which is a process with a relatively low activation barrier, has not been used for the synthesis of chiral amines, since the achiral Schiff base is a major reaction product. However, protected aminoalkynes may undergo an interesting intramolecular allylic cyclization using a palladium catalyst with a chiral norbomene based diphosphine ligand (Eq. 11.9) [115]. Unfor tunately, significantly higher catalyst loadings were required to achieve better enantioselectivities of up to 91% ee. 

As discussed in Sect. 5, the intermolecular hydroamination of alkynes catalyzed by group 4 metal complexes is a well-documented process. The less challenging intramolecular transformation can be achieved efficiently with various titanium-based catalysts [51, 125-130]. The cyclization proceeds analogously to the rare earth metal-catalyzed process with exclusive ej o-selectivity and often requires elevated temperatures. However, the homoleptic titanium tetraamide Ti(NMe2)4 catalyzes the cyclization of both terminal and internal aminoalkynes at room temperature (7) [126, 127]. 

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