Gold intramolecular hydroamination

Scheme 2.16 Gold-catalysed intramolecular hydroamination of alkenes...

Hydroamination of olefins has received considerable attention this year as a route to functionalized piperidines and spiropiperidines, particularly in regard to the investigation of new catalysts. In the synthesis of spiro-piperidines, two new mild and more general intramolecular hydroamination protocols were developed this year. One protocol uses a cationic gold-phosphine complex (Au[P(fBu)2(o-biphenyl)]Cl) as the catalyst... 

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

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 intramolecular hydroamination of trichloroacetimidates derived from propar-gyl and homopropargyl alcohols also proceeds with cationic Au(I) as catalysts. ... 

Mikami and co-workers have reported that axial chirality could be be controlled in gold-bis(phosphanyl)biphenyl (biphep) (213) complexes in a highly stereospecific manner by using the chiral, binaphthol-derived phosphate anion (X ) (200, 214-219), and that the high levels of enantios-electivity could be attained in the intramolecular hydroamination reaction using the enantiopure complexes (Scheme 60). ... 

General procedure for the gold-catalyzed intramolecular hydroamination of alkynyl-... 

An intramolecular gold-catalyzed hydroamination took place upon heating of cyclic dienes bearing a sulfonamide side chain with PhsPAuCl and AgOTf. In this case, 1,4-addition of the amide leads to the formation of hexahydroindoles and related heterocycles. The presence of the bulky phenyl groups in the tether is crucial for... 

Representative procedure for the gold-catalyzed intramolecular hydroamination of cyclic dienes. Cis-3,3-diphenyl-l-(phenylsulfonyl)-l,3,3a,4,5,7a-hexahydro-lH-indol ... 

In one of the first examples of gold-catalyzed hydroamination, Utimoto reported the gold(III)-catalyzed intramolecular hydroamination of 5-alkynyl amines to form... 

Utimoto has also shown that simple gold(III) salts catalyze the intramolecular hydroamination of alkynes with arylamines [4]. For example, treatment of 2-(3,3-dimethyl-l.butynyl)aniline with a catalytic amount of sodium tetrachloroaurate in refluxing TH F for 30 min led to isolation of 2-f-butylindole in 90% yield (Eq. (11.3)). Marinelli has modified and expanded the scope of Utimoto s procedure through employment of ethanol, ethanol/water [5], or ionic liquids 6] solvents. As an example of this modified protocol, treatment of 2-alkynylaniline 2 with a catalytic amount of NaAuCU dihydrate in ethanol at room temperature for 6h led to isolation of 2-(4-chlorophenyl)indole 3 in 92% yield (Eq. (11.4)). A similar hydroamination protocol employing AUCI3 as a catalyst has been recently reported by Majumdar [7]. 

Carbamates are also effective nucleophiles for the gold(I)intramolecular hydroamination of alkynes [12]. For example, treatment of O-propargylic carbamate 10 with a catalytic 1 1 mixture of (PPh3)AuCl and AgOTf in dichloromethane at room temperature led to isolation of 2,5-dihydroisoxazole 11 in 88% yield (Eq. (11.8)). The transformation was effective for alkyl-, alkenyl- and aryl-substituted internal alkynes and terminal alkynes and for N-Boc, Cbz, and Ts derivatives. A similar... 

Iwasawa has reported the gold(III)-catalyzed reaction of N-(o-ethynylphenyl)imi-nes with electron-rich alkenes to form polycyclic indole derivatives [26]. As an example, reaction of N-[l-(l-pentynyl)phenyl]imine 28 and tert-butyl vinyl ether with a catalytic amount of AuBrs in toluene at room temperature led to isolation of the polycyclic indole 29 in 80% yield as a mixture of diastereomers (Scheme 11.3). Conversion of 28 to 29 presumably occurs via initial intramolecular hydroamination to form the gold carbene containing azomethine ylide 30 that undergoes intermo-lecular [3 + 2] cydoaddition with tert-butyl vinyl ether to form the carbene complex 31. 1,2-Migration of the 7t-propyl group to the metal-bound carbon atom coupled with deauration then forms 29. This transformation is also catalyzed efficiently by PtCl2 [26]. 

Bender and Widenhoefer have reported the room temperature intramolecular hydroamination of unactivated alkenes with N,N -disubstituted ureas catalyzed by a gold(I) N-heterocyclic carbene complex [54], For example, treatment of 2-isopropyl-4-pentenyl urea 78 with a catalytic 1 1 mixture of (IPr)AuCl and AgOTf at room temperature for 22 h led to isolation of pyrroldine 79 in 98% yield as a 5.5 1 mixture of diastereomers (Eq. (11.45)). Gold(I)carbon atoms and was effective for the cycHzation of unsubstituted 4-pentenyl ureas and 5-hexenyl ureas. Conversely, the method did not tolerate substitution at the terminal alkenyl carbon atom. 

In contrast to the hydroamination of alkenes with sulfonamides, the potential of an acid-catalyzed reaction pathway in the hydroamination of alkenes with carboxamide derivatives appears less likely. Hartwig found that the intramolecular hydroamination of alkenes with N-arylcarboxamides was only realized in the presence of stoichiometric amounts of triflic add [50]. In contrast, He reported that triflic add catalyzes the intramolecular hydroamination of an N-4-methyl-4-pentenyl carbamate in toluene at 85 °C [55]. However, in the corresponding gold(I)-catalyzed transformation, the intramolecular hydroamination of an N-4-methyl-4-pentenyl carbamate was markedly slower than was the intramolecular hydroamination of an N-4-pentenyl carbamate [52], which is inconsistent with the antidpated behavior of an acid-catalyzed pathway. Furthermore, control experiments firmly ruled out the presence of an acid-catalyzed reaction pathway in the gold(I)-catalyzed intramolecular hydroamination of alkenes with carboxamide derivates and ureas [53, 54]. 

Widenhoefer and Bender have recently reported the gold(I)-catalyzed intramolecular hydroamination of unadivated C=C bonds with alkyl ammonium salts [56]. As an example, treatment of the HBF4 salt of 2,2-diphenyl-4-pentenyl amine (80 HBF4) with a catalytic 1 1 mixture of the gold(I) o-biphenyl phosphine complex (81)AuCl (81 = 2-dicyclohexylphosphino-2, 6 -dimethoxy-l,l -biphenyl) and AgOTf in toluene at 80 ° C for 24 h followed by basification with NaO H led to isolation of pyrrolidine 82 in 94% yield (Eq. (11.46)). Although the transformation was oflimited scope, gold(I)-catalyzed intramolecular hydroamination was also effective for primary 5-hexenyl ammonium salts and secondary 4-pentenyl ammonium salts. 

Scheme 9.16 Gold-catalyzed intramolecular hydroamination according to Bender and Widenhoefer [35],...

Scheme 16.55 Gold-mediated intramolecular hydroamination of aminoallenes to form pyrrolidines and piperidines.

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... 

In recent years, several groups have developed enantioselective tandem reactions based on the combination of gold catalysis and organocatalysis. Among them, Gong et al. reported that an achiral gold complex compatibly worked with a chiral phosphoric acid to promote a domino intramolecular hydroamination-reduction reaction, readily transforming... 

Scheme 7.30 Domino intramolecular hydroamination-reduction reaction catalysed by chiral phosphoric acid catalysis and gold catalysis.

In 2010, Gong et al. reported a highly enantioselective three-component domino reaction, consisting of an enantioselective aza-Diels-Alder cycloaddition catalysed by a chiral phosphoric acid and a subsequent intramolecular hydroamination catalysed by a gold complex. The domino reaction occurred between aldehydes, an enamide, and 2-(2-propynyl)aniline... 

Gong and coworkers coupled an organocatalyzed sequential Povarov reaction, occurring with high yield and enantioselectivity, to a gold-catalyzed intramolecular hydroamination, affording julolidine derivatives 218 (Scheme 42.50). The authors showed that no gold species is involved in the cycloaddition reaction [108]. 

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. 

Han Z-Y, Xiao H, Chen X-H, Gong L-Z. Consecutive intramolecular hydroamination/asymmetric transfer hydrogenation under relay catalysis of an achiral gold complex/chiral brpnsted acid binary system. J. Am. Chem. Soc. 2009 131 9182-9183. 

A related gold(I)-catalysed intramolecular hydroamination and ring-opening of sulfonamide-substituted 2-(arylmethylene)cyclopropylcarbinols (252), giving rise to isoxazolidines (253), has also been reported. ... 

---