Gold hydroamination

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

Kovacs, G., Ujaque, G. and Lledos, A. (2008) The Reaction Mechanism of the Hydroamination of Alkenes Catalyzed by Gold(I)-Phosphine The Role of the Counterion and the N-Nucleophile Substituents in the Proton-Transfer Step. Journal of the American Chemical Society, 130, 853-864. 

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... 

An interesting example of a gold-catalyzed cycloisomerization of P-aminoallene 168 to tetrahydropyridine 169 is depicted below <06OL4485>. Patil et al. report a similar gold-catalized hydroamination of allenes to produce 2-vinyl piperidine 170 in good yield <06TL4749>. 

Similarly, Vasudevan and Verzal have found that terminal alkynes can be hydrated under neutral, metal-free conditions using water as solvent (Scheme 4.15) [41], While this reaction typically requires a catalyst such as gold(III) bromide, employing microwave-superheated distilled water allowed this chemistry to proceed without any catalyst. Extension of this methodology led to a one-pot conversion of alkynes to imines (hydroamination). 

The cationic gold complex with CAAC ligand 29 can also catalyze the unprecedented hydroamination reaction of alkynes and allenes using ammonia [59, 60]. It was also demonstrated that it can catalyze the simple hydroamination reaction. It... 

The excellent ability of late transition metal complexes to activate alkynes to nucleophilic attack has made them effective catalysts in hydroamination reactions. The gold(l)-catalyzed cyclizations of trichloroacetimidates 438, derived from homopropargyl alcohols, furnished 2-(trichloromethyl)-5,6-dihydro-4f/-l,3-oxazines 439 under exceptionally mild conditions (Equation 48). This method was successfully applied to compounds possessing aliphatic and aromatic groups R. With R = Ph, cyclization resulted in formation of 439 with complete (Z)-stereoselectivity <2006OL3537>. 

Table 3 Phosphine-gold(i)-catalyzed isomerization and hydroamination reaotion of sulfonamides...

Hydroamination of Allenes Different related amines can also be cyclized. The use of free amino groups led to long reaction times (several days), but sulfonamides, acetyl or BOc as protecting group led to fast conversion (in the latter case, problems of diastereoselectivity were observed). Optimization studies showed that, although cationic gold (I) complexes were not effective for these conversions, AuCI was a very good catalyst for these reactions. 

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

At the end of 2007, Widenhoefer et al. reported the first examples of the dynamic kinetic enantioselective hydroamination of axially chiral allenes, catalyzed by a dinuclear complex of gold (Figure 8.1) and silver perchlorate [46, 47]. 

Figure 8.1 Gold complex used as catalyst for the hydroamination of axially chiral allenes.

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). 

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,... 

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. ... 

Scheme 11.24 Chiral counteranion effect on the gold catalyzed hydroamination/cyclization of aminoallenes [118],...

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

Hydroamination. On complexing to (/J)-xylyl-BINAP gold p-nitrobenzoate activates a double bond of an aUene moiety to allow intramolecular attack by an amino group, asymmetrically. 

Gold-catalyzed organic reactions, particularly, olefin epoxydation and hydroamination or hydroalkoxylation of alkynes to give N- or O-het-... 

Gold-catalyzed hydroamination of C-C multiple bonds, particularly, in synthesis of N-heterocycles 06EJO4555. 

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. 

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). ... 

The synthesis of benzo[f ][l,4]diazepines 66 by a tandem hydroamination-cychzation sequence was carried out using a gold(I)-N-hetereocyclic car-bene catalyst (14JOM438). The authors utilized readily available N-alkyl o-phenylenediamines 63 and arylacetylenes 64 as starting materials. They proposed that the reaction proceeds by amination of a gold-activated alkyne with subsequent cyclization of intermediate 65. 

A-vinylindoles took place. Moreover, the gold-catalyzed cyclization of 2-alkynylanilines can be combined with a gold-catalyzed Michael addition to enones, which afforded 3-alkylated indoles with good yield. Gold-catalyzed hydroamination/hydroarylation cascades of polyenyne-substituted anilines leading to condensed aromatics have been described recently. ... 

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