Aminoalkynes

Siiylcupration also works witli 1-aminoalkynes [70], propargyl sulfides [71], prop-argyl amines [14a, 72] - where it bas been exploited in tlie syntliesis of saturated and Linsaturated j -s dyl-a-amino acids iSdieme 3.17) - and propargyl ediers, where... 

Similar reactions with primary and secondary amines result in the formation of 3-aUcylamino- or 3-dialkylamino-l-butyne in 30-80% yield (TON = 3-9) [243-247]. In one example, the TOP could be estimated as 0.2 h" [246]. Enamines were proposed as reaction intermediates. It was later shown that enamines effectively react with terminal aUcynes, including acetylene, to afford the expected aminoalkynes without catalyst or, more rapidly, sometimes exothermically, in the presence of CujCf [248]. Aromatic amines do not react under the same conditions. However, in the presence of organic acids, e.g. acetic acid, 3-arylamino-l-butynes can be isolated in moderate yields (Eq. 4.59) [246, 247, 249]. 

Scheme 4-14 Catalytic cycle for the IH of aminoalkynes via activation of the alkyne...

IH of aminoalkynes can be performed under mild conditions using CpTiCb or CpTi(Me)2Cl as catalyst precursors to give dihydropyrrole and tetrahydropyridine derivatives (regioselective Exo-Dig processes) in high yield with TOE near 10 h (e.g., Eq. 4.79) [297]. 

Aminotroponiminato)yttrium amides also catalyze the regioselective IH of primary aminoalkynes of Eq. (4.79), but the catalytic activity is lower (TOE < 1 h ) [300]. 

Organolanthanides are efficient catalyst precursors for the regioselective (>95%) IH of primary aminoalkynes, forming five-, six-, and seven-membered cyclic imines via Exo-Dig processes (Eq. 4.86) [303, 304]. 

The initial reaction has been extended to the IH of secondary aminoalkynes to give cyclic enamines with an exocyclic C=C bond [304]. 

The ring-size dependence of the cyclization rate (TOE) is 5 > 6, as already observed for IH of aminoalkenes and aminoalkynes. 

With regard to TOE, the IH of aminoaUenes is significantly more rapid than that of the corresponding aminoalkenes, but slower (ca. 5-20 times) than that of the corresponding aminoalkynes. 

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... 

Alkynes can also serve as the recipient of cycloamination protocols. For example, 2,4-disubstituted pyrroles 180 are formed in high yields from Pd-cataJyzed cyclization of aminoalkynes 179 [127]. Less effective is Pd(Ph3P)4 but Pd(OAc)2 works as well as PdCh. 

The Sonogashira reaction of 5-bromopyrimidine with ]V,lV-dimethylpropargylamine gave aminoalkyne 81 [59], whereas the union of 6-methyl-2-phenyl-4-iodopyrimidine and 3,3,3-triethoxy- 1-propyne afforded ester 82 after acidic hydrolysis [60]. 

The ring closure of aminoalkynes bearing a leaving group in the appropriate position might lead to the formation of pyrroles in an addition-elimination sequence. 2-Phcnylcthynyl-1 -amino-sec-butanol. for example, gave 4-ethyl-2-phenylpyrrole on treatment with palladium dichloride in acetonitrile in excellent yield (3.46.),57... 

Reaction of isatoic anhydride with a-aminoalkynes gave 209, which cyclized to a mixture of the oxazolo[3,2-b]quinazolines (210) and 2-aminophenyloxazoles (211) upon treatment with phosgene (89JHC1495). 

Cyclizations with nitrogen nucleophiles involving alkynes and allenes have received little attention until recently. The cyclizations of several a-aminoallenes to 3-pyrrolines with silver tetrafluoroborate was reported by Claesson and coworkers (equation 133).264 A similar cyclization to form A -carba-penems has been reported (equation 134).265 Diastereomeric allenes (R1 R2) were shown to cyclize with complete stereocontrol. Cyclization with palladium chloride in the presence of allyl bromide or electrophilic alkenes allowed for the intermediate vinylpalladium species to be trapped by the electrophile.2651 A related product was obtained by cyclization of an alkynic substrate (equation 13S).265 Other examples of 5-endo cyclization of p-aminoalkynes50 include the formation of indoles by cyclization of 2-alkynylanilines with mercury salts200 or palladium chloride,266a,266b,266c formation of 1-pyrrolines with catalytic palladium chloride (equation 136)198 and formation of pyrroles by cyclization of hydroxy-substituted p-aminoalkynes.198,2666... 

Keywords alkyne, amine, paraformaldehyde, alumina, Mannich condensation, microwave irradiation, aminoalkyne... 

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%. 

Aminoalkenes, oxidative cyclization, 10, 710-711 Aminoalkoxides, on zinc compounds, 2, 371 a-Aminoalkylallenes, cycloisomerizations, 10, 720 a-Aminoalkylcuprates, preparation, 9, 519-520 -Aminoalkylidynes, diiron carbonyl complexes with cyclopentadienyl ligands, 6, 248 Aminoalkynes, hydroamination, 10, 717 a-Aminoallenes, activation by gold, 9, 574 Amino r]5-amides, in Ru and Os half-sandwich rf3-arenes,... 

The same type of precatalysts catalyze the regiospecific hydroamination/ cyclization of aliphatic and aromatic aminoalkynes RC=(CH2) NH2 [295]. The mechanistic scenario parallels that of the corresponding aminoolefin cyclization. However, the cyclization of the aminoalkynes is 10-100 times more rapid, and a rather contrary effect of the cyclopentadienyl substitution on N, was observed. 

Scheme 13. Organosamarium-catalyzed hydroamination and cyclization of aminoalkynes...

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]. 

Conjugated heterocumulenes can act as heterodimers in [4+2] cycloadditions, reacting with aminoalkynes to give tetrasubstituted pyridines (Equation 111) <1997T4521>. The corresponding isoquinoline is formed if the reaction is heated to 140 °C. 

Generally, insertion of the alkyne into a metal-P bond is observed (Scheme 10).188,190 When aminoalkynes are used, the formation of a C=N double bond inhibits the interaction of that carbon with the metal centers of the cluster.186 187 When two PR groups are present, the alkyne has been observed to bridge between them as seen in Scheme 10.195,285 A second equivalent of diphenylacetylene can substitute for two carbonyl groups on the iron triangle.195 The hetero-main group element species Fe3(CO)9(NPh) (P Bu) and Fe3(CO)9(NPh)2 have been reacted with diphenylacetylene.273 Some of the products involved in the acetylene addition reaction are shown here (241-243). 

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... 

Similar cyclic imines can be synthesized by intramolecular oxidative amination of aminoalkenes, which are less expensive than aminoalkynes. In the presence of catalytic amounts of [RuCl2(CO)3]2/l,3-bis(diphenylphosphino)propane and excess K2C03/allyl acetate, various aminoalkenes 19 possessing substituent(s) f3 to the amino group afforded five- and six-membered cyclic imines 20 in mod-erate-to-excellent yields (Eq. 8) [14]. 

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>. 

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