Acetylene hydroamination

It was probably Kozlov et al., studying the condensation of acetylene with aniline, who observed the first homogeneously catalyzed hydroamination of an alkyne [239]. They give experimental evidence that N-phenylethylideneamine is an intermediate, which evolves to an aldol-type condensation product (Scheme 4-9), known as an Ek-stein-Eibner base [240-242]. 

Scheme 4-10 Hydroamination product as intermediate in the reaction of acetylene and Et2N H...

Under the same conditions, the hydroamination of acetylene with primary or secondary aromatic amines brings about the formation of dimerization-cyclization products since the generated imines or enamines, respectively, are not stable. 

The Cp 2ThMe2 analog catalyzes the hydroamination of acetylene with EtNH2 (Eq. 4.83) [301]. 

Hydroamination of Alkynes The discovery of palladium-catalyzed intramolecular addition of amines to acetylene coupled with the spectacular contribution of Hutchings opened the door for the synthesis of several nitrogen heterocycles. The first study in this field was performed by Utimoto et al., who researched gold catalyzed intramolecular 6-exo-dig hydroamination. Tautomerization of the initial enamines allowed them to obtain imines, which were thermodynamically more stable [111] (Scheme 8.20). 

A number of additional cyclizations involving alkynes have been reported. For instance, it has been shown that indoles may also be accessed from 2-bromo- or 2-chloroanilines, as illustrated by the regioselective preparation of the carbinol 373 in the presence of the ferrocene 374 (Equation 104) <20040L4129>, whereas a one-pot sequence featuring titanium catalyzed hydroamination of 2-chloroanilines with acetylenes, followed by intramolecular Heck cyclization in the presence of an imidazol-2-ylidene palladium complex, has also been reported <2004CC2824>. A set of aryl-2-indolyl carbinols have been prepared in high enantiomeric purity by palladium-catalyzed annulation of... 

Imines react with alkynes to give pyrroles (equation 29). " A related transformation of azides has been reported by the group of Toste to afford pyrroles by an acetylenic Schmidt reaction (equation 30). " In an intermolecular-related addition, gold triazolates are obtained. The intramolecnlar hydroamination of trichloroacetimidates derived from propar-gyl and homopropargyl alcohols also proceeds with cationic An(I) as catalysts. ... 

The first intermolecular hydroamination of an alkyne was reported by Uchimaru in 1999 [92]. It was found that Ru3(CO)i2 catalyzes the reaction of N-methylaniline derivatives with phenyl-substituted acetylenes in good yields (76-88%)(Scheme 8.31). 

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... 

An intramolecular Pd(0)/benzoic acid-catalyzed hydroamination of acetylene 259 afforded the indolizidme 260 as a single diasteieomer. Saturation of the double bond gave the alkaloid (-)-209D <05TL2101> (Scheme 78). 

The Au(III)-catalyzed double hydroamination cascade reaction of ortho-alkynyla-nilines 167 with terminal alkynes 168 affording N-vinylindoles 169 was reported by li (Scheme 9.63) [221]. In the case of alkyl-substituted acetylenes, this protocol provided mixtures of isomeric N-vinylindoles with both terminal and internal double bonds. This transformation is believed to occur via the Au(III)-catalyzed cydoisomerization of transient key alkynyl imines, similar to 162 utilized by Yamamoto, which were generated via the initial Au(111)-catalyzed hydroamination of the corresponding anilines 167 with alkynes 168. 

Trimetallic palladium and gold earbene complexes structured around a triphenylene scaffold (13) have been synthesized and used in ct-arylation of propiophenone, Suzuki-Miyaura reactions and hydroamination of acetylene. They exhibited an enhanced reactivity compared to other trimetallic as well as more conventional monometallic complexes. This enhancement is thought to arise from the specific topological properties that might favour the interaction between the catalysts and the aromatic substrates as... 

A-Alkylation of amides and amines and dehydrative -alkylation of secondary alcohols and a-alkylation of methyl ketones " have been carried out by an activation of alcohols by aerobic oxidation to aldehydes, with copper(II) acetate as the only catalyst. A relay race process rather than the conventional borrowing hydrogen-type mechanisms has been proposed for the aerobic C-alkylation reactions, based on results of mechanistic studies. A Winterfeldt oxidation of substituted 1,2,3,4-tetrahydro-y-carboline derivatives provides a convenient and efiflcient method for the synthesis of the corresponding dihydropyrrolo[3,2-fc]quinolone derivatives in moderate to excellent yields. The generality and substrate scope of this aerobic oxidation have been explored and a possible reaction mechanism has been proposed. Direct oxidative synthesis of amides from acetylenes and secondary amines by using oxygen as an oxidant has been developed in which l,8-diazabicyclo[5.4.0]undec-7-ene was used as the key additive and copper(I) bromide as the catalyst. It has been postulated that initially formed copper(I) acetylide plays an important role in the oxidative process. Furthermore, it has been postulated that an ct-aminovinylcopper(I) complex, the anti-Markovnikov hydroamination product of copper acetylide, is involved in the reported reaction system. Copper(I) bromide... 

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