Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• -alanine. The key step to access the enantiopure pyridone intermediate was achieved by a gold-mediated cyclization. Finally, various transformations afforded the natural product in a few steps and good overall yield. Keywords: epimyrtine; gold; gold catalysis; heterocycles; hydroamination; quinolizidine

• renders gold catalysis a straightforward protocol in the realm of the synthesis of natural products [17][18]. Herein we report a short total synthesis of (−)-epimyrtine employing an alternative strategy by using a gold(I)-catalyzed hydroamination of a β-aminoynone as the key step. Actually, cyclization of

• lithium acetylide to furnish the β-aminoynone 2 with a yield of 71%. With this key building block in hand, efforts were directed toward the gold-mediated intramolecular hydroamination for the construction of the chiral pyridone intermediate 3. For this, PPh3AuSbF6 generated in situ from a 5 mol % mixture

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• Saint-Aignan, France 10.3762/bjoc.9.168 Abstract A concise and regioselective preparation of 2-heteroarylmethylene decorated N-arylpyrroles is described through a metal-free Mannich/Wittig/hydroamination sequence followed by isomerization of the N-arylpyrrolidine adducts. Furthermore, the C–H

• recently described a one-pot organo-catalyzed synthesis of N-heteroarylmethylene pyrrolidines 4 [13] from readily available aldehydes 1 and imine 2 by a sequence of Mannich coupling [14][15][16][17][18][19][20][21][22][23][24], Wittig olefination with phosphonium 3, and proton-mediated hydroamination

• high yield (91%). The Mannich coupling was next attempted with different imines 2b–e in order to modulate the nature of the aryl moiety (Scheme 4). The electronic nature of the aniline being crucial for the stability of the imine and the hydroamination step, electronically rich anilines were selected

Gold-catalyzed intermolecular hydroamination of allenes with sulfonamides

• Chen Zhang,
• Shao-Qiao Zhang,
• Hua-Jun Cai and
• Dong-Mei Cui

Beilstein J. Org. Chem. 2013, 9, 1045–1050, doi:10.3762/bjoc.9.117

• the intermolecular hydroamination of allenes with sulfonamides is shown. The reaction proceeded smoothly under mild conditions for differently substituted allenes giving N-allylic sulfonamides in good yields with high regioselectivity and E-selectivity. Keywords: allene; gold catalysis

• ; hydroamination; N-sulfonyl; selectivity; sulfonamide; Introduction Hydroamination of an N–H bond across a C–C unsaturated bond represents one of the most effective and atom-economical methods to prepare amine derivatives [1][2][3][4][5]. In the case of using allenes, this reaction can lead to allylamines, which

• are invaluable precursors for the synthesis of natural products and other potentially biologically relevant substances [6]. In the literature, a wide range of catalytic intramolecular hydroaminations of allenes are known, but only a small number of intermolecular hydroamination reactions are reported

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• reaction times and displayed limited reaction tolerance and low reaction selectivity [20][21]. Cheeseman and Tuck reported the first pyrrolo[1,2-a]quinoxaline in 1965 [22]. Recently, Patil et al. developed the PtBr2 and Au(I)-catalyzed hydroamination–hydroarylation cascade reactions of 2-(1H-pyrrol-1-yl

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• hydroamination of the allenes 39, easily accessible by prototropic isomerization of the corresponding propargylamides (Scheme 20) [78]. The selective 5-exo-allylic hydroamination occurs in mild conditions in the presence solely of Pd(PPh3)4 under microwave irradiation by an initial coordination of the Pd(0

• ]indole skeleton by intramolecular C-2 alkenylation. Synthesis of azepinoindoles by oxidative Heck cyclization. Enantioselective synthesis of 4-vinyl-substituted tetrahydro-β-carbolines. Pd-catalyzed endo-cyclization of 3-alkenylindoles for the construction of carbazoles. Pd-catalyzed hydroamination of 2

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

•  5) [38]. This reaction is important for the hydroamination of alkynes by Cp2ZrX2 complexes, which proceeds through zirconium imido intermediates [39]. A similar [2 + 2] cycloaddition of symmetrical alkynes across a tungsten nitride is the initial step in Johnson's nitrile-alkyne cross metathesis

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• chiral NHC–Au(I) complexes (4–6) with a binaphthyl or biphenyl framework [13][14]. These Au(I) complexes were applied to catalyze the asymmetric cyclization of 1,6-enynes or allene in up to 70% ee, and the asymmetric intramolecular hydroamination of allene in up to 44% ee. We previously reported a novel

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• attempted Pd-catalyzed deallylation of N-allyl-3-sulfonylpyrrolidines in the presence of 2-mercaptobenzoic acid according to the procedure developed by Genêt and coworkers [24] (Scheme 21). Amines as coupling partners through hydroamination of alkyne derivatives Many synthetic methods for the preparation of

• coupling of aryl chlorides. This was followed by an intramolecular alkyne–hydroamination (addition of an N–H bond across a carbon–carbon multiple bond) leading to the corresponding indole derivatives 52. The amination/alkyne–hydroamination sequence requires the addition of 1.5 equiv of t-BuOK to reach

• amines [31]. This is followed by an in situ intramolecular hydroamination of the resulting amide on the triple bond, leading to substituted 3-methyleneisoindolin-1-ones in high selectivities in favor of the (Z)-isomers (Scheme 24). A palladium-mediated three-component process for the preparation of

Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles

• Antoine Simonneau,
• Pierre Garcia,
• Jean-Philippe Goddard,
• Virginie Mouriès-Mansuy,
• Max Malacria and
• Louis Fensterbank

Beilstein J. Org. Chem. 2011, 7, 1379–1386, doi:10.3762/bjoc.7.162

• the synthesis of 3-fluoro-2-methylene-pyrrolidine (3a) and -piperidine (3b) from 1,5- and 1,6-aminoalkynes, respectively, using a combination of a gold-catalyzed hydroamination reaction followed by electrophilic trapping of an intermediate cyclic enamine by Selectfluor. Careful attention was paid to

• explained either by direct fluorination of the enamine resulting from the gold-promoted alkyne hydroamination or by oxidation of the intermediate vinyl gold(I) complex by Selectfluor into a gold(III) fluoride species followed by a reductive elimination. Moreover, the formation of C(sp2)–F bonds, either by

Efficient gold(I)/silver(I)-cocatalyzed cascade intermolecular N-Michael addition/intramolecular hydroalkylation of unactivated alkenes with α-ketones

• Ya-Ping Xiao,
• Xin-Yuan Liu and
• Chi-Ming Che

Beilstein J. Org. Chem. 2011, 7, 1100–1107, doi:10.3762/bjoc.7.126

• - [11][12][13][14][15], nitrogen- [10][16][17][18] (for recent reviews on gold-catalyzed hydroamination see [16][17][18]), or carbon-nucleophiles [19][20][21][22][23][24] to unactivated alkenes [21][22][23][24][25] have been developed. On the other hand, in recent years, considerable efforts have been

Triazole–Au(I) complex as chemoselective catalyst in promoting propargyl ester rearrangements

• Dawei Wang,
• Yanwei Zhang,
• Rong Cai and
• Xiaodong Shi

Beilstein J. Org. Chem. 2011, 7, 1014–1020, doi:10.3762/bjoc.7.115

• improved thermal stability and substrate stability in the gold(I) promoted hydroamination and Hashmi phenol synthesis [42], which makes them interesting novel catalysts in the field of gold catalysis. One particular new development of the TA–Au catalysis that attracted our attention was the synthesis of α

Intramolecular hydroamination of alkynic sulfonamides catalyzed by a gold–triethynylphosphine complex: Construction of azepine frameworks by 7-exo-dig cyclization

• Hideto Ito,
• Tomoya Harada,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2011, 7, 951–959, doi:10.3762/bjoc.7.106

• Hideto Ito Tomoya Harada Hirohisa Ohmiya Masaya Sawamura Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan 10.3762/bjoc.7.106 Abstract The gold-catalyzed, seven-membered ring forming, intramolecular hydroamination of alkynic sulfonamides has been

• cyclization to afford the nitrogen-containing heterocyclic seven-membered rings, such as tetrahydroazepine and dihydrobenzazepine, in good yields. Keywords: azepine; cyclization; gold catalyst; hydroamination; triethynylphosphine; Introduction Nitrogen-containing heterocyclic seven-membered rings are found

• for the construction of N-heterocyclic compounds, metal-catalyzed intramolecular hydroamination of unactivated C–C multiple bonds is particularly straightforward and efficient [17][18]. Specifically, gold-catalyzed intramolecular hydroaminations of alkynes, alkenes and allenes show remarkable

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• obtained in all cases. A similar Markovnikov hydroamination [59] could also be achieved via an intermolecular hydroamination of allenamides 123 with arylamines under mild AuPPh3OTf catalysis conditions to furnish allylamino (E)-enamides stereoselectively (Scheme 22). Hesp and co-workers have identified a

• gold pre-catalyst 125 featuring a P,N-ligand that has significantly extended the substrate scope and synthetic utility of alkyne hydroamination [60]. The hydroamination of unsymmetrical internal aryl acetylenes 126 with dialkylamines 127 has been achieved with synthetically useful regioselectivities

• played an activation role but also acted as a reactant in the reaction (Scheme 32). A simple, convenient, and green synthetic approach to diverse fused xanthines 182 has also been developed by gold-complex catalyzed intramolecular hydroamination of terminal alkynes 181 under microwave irradiation in

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• and trapping of the carbocation by the sulfonamide. Subsequent intramolecular hydroamination gave the pyrrolidine products. 1.3 Oxiranes As an oxophilic Lewis acid, gold can activate epoxides towards the attack of nucleophiles. A good example is the AuCl3 catalyzed ring opening of aryl alkyl epoxide

Sequential Au(I)-catalyzed reaction of water with o-acetylenyl-substituted phenyldiazoacetates

• Lei Zhou,
• Yizhou Liu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2011, 7, 631–637, doi:10.3762/bjoc.7.74

• chemical processes in the fine chemical industry. In this context, we have previously reported the copper(I)-catalyzed reaction of amines with o-acetylenyl-substituted phenyldiazoacetates, which leads to a Cu(I)-catalyzed tandem N–H insertion/hydroamination of an alkyne [29]. Subsequently, we have tried to

Synthesis of chiral mono(N-heterocyclic carbene) palladium and gold complexes with a 1,1'-biphenyl scaffold and their applications in catalysis

• Lian-jun Liu,
• Feijun Wang,
• Wenfeng Wang,
• Mei-xin Zhao and
• Min Shi

Beilstein J. Org. Chem. 2011, 7, 555–564, doi:10.3762/bjoc.7.64

• showed good catalytic activities in the asymmetric intramolecular hydroamination reaction to give the corresponding product in moderate ee. Keywords: chiral mono(N-heterocyclic carbene) complex; Heck–Mizoroki reaction; hydroamination; Suzuki–Miyaura reaction; Introduction N-heterocyclic carbene (NHC

• activities in the reaction of arylbromides or iodobenzene with n-butyl acrylate to afford the coupling products 10 in up to 97% yield. The results have been summarized in Table 2. Intramolecular hydroamination reaction catalyzed by NHC–Au(I) complex (S)-6a Since the first example of NHC–Au complex was

• NHC–Au(I) complex (S)-6a was consequently investigated as the catalyst in the asymmetric intramolecular hydroamination of allenes. This reaction has been achieved with high enantioselectivity by a chiral phosphine–Au(I) complex [87][88][89][90][91][92][93]. Treatment of allene 11 with (S)-6a and

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• hydroamination reactions [66]. Nevertheless, Beller et al. developed a valuable method to overcome these limitations. In 1999 they described the transition metal catalyzed hydroarylation of anilines 46 with styrenes using a cationic Rh-complex [67]. Depending on the aniline derivative, a combination of 2.5 mol

• well [68]. Ackermann et al. attempted to develop a Ti(IV)-catalyzed hydroamination of anilines with olefins, and surprisingly discovered that a mixture of hydroamination and ortho-hydroarylation products was formed. Upon further heating of the secondary amine 48 in the presence of TiCl4 the ortho

The enantiospecific synthesis of (+)-monomorine I using a 5-endo- trig cyclisation strategy

• Malcolm B. Berry,
• Donald Craig,
• Philip S. Jones and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2007, 3, No. 39, doi:10.1186/1860-5397-3-39

• transformations, would be converted into the 2,5-syn disubstituted pyrrolidine core 8 via alkene 7. With all the required carbon atoms in place, the final steps would involve deprotection, intramolecular hydroamination of the alkene and desulfonylation. Initial studies directed towards this goal exploited the

• -Hydride® to give the free amines 23 and 15c, which were subjected to mercury-mediated hydroamination (Scheme 6 and Scheme 7). [20] Cyclisation of 23 proceeded in good yield to give a 9:4 mixture of two indolizidines, epimeric at the C-5 methyl group 24-anti and 24-syn (Scheme 6). Cyclisation of the

• required for the preparation of (+)-monomorine I Mercury-mediated hydroamination Proposed transition state for mercury-mediate hydroamination Model study for the reductive amination-based cyclisation The synthesis of (+)-monomorine I Deprotection of N-benzoylpyrrolidines Supporting Information Supporting