Gold intermolecular hydroamination

Equation 11.12. Stereoselective gold catalyzed intermolecular hydroamination of a chiral allene [122]. 

Synthesis of enantiomerically enriched secondary amines (168) with excellent ee values, through the tandem, intermolecular hydroamination with primary amines (166) /transfer hydrogenation of alkynes (167), using a the gold(I) complex-chiral phosphoric acid (127) protocol, has been developed by Che and Liu (Scheme 44). A wide variety of aryl, alkenyl, and aliphatic alkynes as well as anilines with different electronic properties were tolerated. 

The use of carbamates as the nucleophile allowed extension of the method to the gold-cataWzed intermolecular hydroamination of conjugated dienes at room temperature. The reaction took place regioselectively as 1,2-addition at the less substituted double bond. 

Li has reported that cationic gold(III) complexes also catalyze the intermolecular hydroamination of terminal alkynes with aniline derivatives [17]. For example, reaction of a neat 1 1.5 mixture of phenylacetylene and aniline catalyzed by AUCI3 at room temperature followed by reduction with sodium borohydride led to isolation... 

Yamamoto has also demonstrated the intermolecular hydroamination of mono-substituted arylallenes with morpholine [40]. For example, treatment of l-p-tolyl-1,2-propadiene with morpholine and a catalytic 1 1 mixture of [PPh2(o-tolyl)]AuCl and AgOTf in toluene at 80 °C for 24h led to isolation of the allylic amine 56 in 83% yield as a single regio- and stereo-isomer (Eq. (11.31)). 1-Alkylallenes, 1,1-, and 1,3-disubstituted allenes also underwent gold(I)hydroamination with morpholine, albeit with diminished efficiency and/or regioselectivity. 

In addition to these findings, the most remarkable example of the improvement of the stability of a gold catalyst was reported by Bertrand and coworkers. In their studies of intermolecular hydroamination reactions of allenes and alkynes, which were either conducted with ammonia or hydrazine, they showed that their gold catalysts based on abnormal NHC ligands have amazing thermal stability [38]. Due to the fact that the amines used are capable of coordinating to the open side of the catalytic species and therefore can block the catalyst, these reactions require high reaction temperatures. Therefore, the reactions are carried out at temperatures of 160-200 °C (see Scheme 9.19) [38]. 

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... 

Almost at the same time, Liu and Che independently applied the same strategy to the synthesis of chiral secondary amines through a domino intermolecular hydroamination-transfer hydrogenation of alkynes using a gold(i) complex in combination with a chiral phosphoric acid." This domino process has a broad substrate scope since a wide variety of aryl, alkenyl, and aliphatic allq nes could be coupled with anilines with different electronic properties to afford chiral amines in excellent enantioselectivities of up to 94% ee, as shown in Scheme 7.31. 

Scheme 7.31 Domino intermolecular hydroamination-reduction reaction catalysed by chiral phosphoric acid catalysis and gold catalysis.

Independently, Liu and Che reported the gold(I)/chiral Brpnsted acid-catalyzed tandem intermolecular hydroamination and transfer hydrogenation reactions of alkynes 369 and aryl amines 7, affording chiral secondary amines 371 in high optical purity (Scheme 2.98). Regarding the reaction mechanism, the authors believed that the imine, which was formed in situ from alkyne and aryl amine under gold(I) 370... 

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. ... 

Hydroamination of olefins is also possible with gold catalysts. In this reaction, the attack comes Ifom a nitrogen nucleophile as a carbamate,a urea, an amide, or a sulfonamide. In the latter case, the reaction can be carried out intermolecularly. While the carbamates, ureas, and amides give only products of intramolecular anunations, the sulfonamides can perform the intermolecular addition. Only the addition of ureas (equation 146) takes place at room temperature, and in the rest of the additions heating is required. The catalysts of choice in all these reactions are cationic gold(I)-species stabilized by phosphines or NHC ligands. The reaction times have been reduced by the use of microwave irradiation. The mechanism of the hydroamination reaction has been studied in detail theoretically. ... 

The corresponding intermolecular addition of cyclic ureas to terminal alkenes is catalyzed by Au[P(/-Bu)2(o-biphenyl)]Cl and AgOTf, and it provided alkylated ureas in high yield at 100 °C. The reaction even works with ethylene and other gaseous olefins. In the presence of chiral gold(I) pre-catalyst [Au2 (S)-3,5-r-Bu-4-MeO-MeOBIPHEP Cl2] and silver triflate, the hydroamination products were obtained with 71-76% ee (Scheme 4-68). Treatment of cyclic ureas with allylic alcohols in the presence of cationic gold(I) catalysts afforded allylated ureas with... 

Indeed, Cu can be used in combination with tungstophosphoric acid to realize solvent-free acid-catalyzed hydroarylation and hydroamination of alkynes to give the Markovnikov products with a variety of arylamines [211]. Furthermore, gold catalysts have been used extensively with acid additives for a variety of amine and protected amine substrates [120,212]. More recently, Bertrand [189] was able to illustrate the useful apphcation of his [(CAACjAulBlCgFj) complex for intermolecular alkyne hydroamination with both primary and secondary amines (Table 15.14). 

Table 15.15 Intermolecular alkyne hydroamination catalyzed by gold-phosphine complexes.

Nishina N, Yamamoto Y (2008) Gold-catalyzed intermolecular hydroalkoxylation of allenes difference in mechanism between hydroalkoxylation and hydroamination. Tetrahedron Lett 49 4908 911... 

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