Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• desired 6b in 96% yield. The reaction worked also with 5c and 5d bearing a cyclohexyl bridge, delivering the desired products 6c and 6d in 78% and 72% yields, respectively (Table 3, entries 2 and 3). We tested the reaction with the benzenoid substrates 5e–5g, giving the corresponding enones 6e–6g in 63–78

A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand

• Hideki Shimizu,
• Jeffrey C. Holder and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2013, 9, 1637–1642, doi:10.3762/bjoc.9.187

• ][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Recently, our laboratory reported the catalytic asymmetric conjugate addition of arylboronic acids to cyclic, β,β-disubstituted enones utilizing (S)-t-BuPyOx (1) as the chiral ligand (Figure 1) [24]. This robust reaction is

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• to C14–C15 of ripostatin A instead was sought. Oxy-Michael approach to epoxide We were intrigued by a recent report by Falck describing an organocatalytic oxy-Michael addition to achiral δ-hydroxy-α,β-enones (Scheme 12) [52]. The hydroxy group is delivered in a directed fashion from the boronic acid

• around the enone. Aliphatic enones react more sluggishly in this transformation; however, 3,4,5-trimethoxyphenylboronic acid may be used as a more efficient nucleophilic partner to circumvent this limitation. Application of this transformation to the ripostatin A epoxide fragment 5 allows installation of

• well tolerated for the reaction using γ-hydroxy-α,β-enones. Although the presence of chirality at the δ-position allows for diastereoselective intramolecular oxy-Michael addition of hemiacetal-derived alkoxides into α,β-unsaturated esters, the extension of this reaction to ketones was not successful

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• synthesis; catalysis; enones; intramolecular aza-[3 + 3] annulation; N-heterocycles; natural product; vinylogous amides; Introduction Throughout the past decade, we have been developing an aza-[3 + 3] annulation reaction as a general and unified strategy in alkaloid synthesis [1][2][3][4][5][6][7][8][9][10

• employ vinylogous amides tethered to α,β-unsaturated ketones, or enones 1b (R ≠ H) (Scheme 1). Conceptually, employing enals or enones in an aza-[3 + 3] annulation appears to constitute very little difference, with the major difference lying in the R group in their respective products 3 and 4. While

• seemingly an insignificant perturbation, the ability to employ enones in aza-[3 + 3] annulations can generate a vast array of opportunities, including the case where R is as small and simple as a Me group, which would already represent a facile entry to aza-phenylene alkaloids [30][31][38][39][40][41][42

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• , France Clermont Université, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand, France 10.3762/bjoc.9.52 Abstract A general and simple procedure to access chiral β'-amino-α,β-enones, in seven steps, from an α,β unsaturated ester has been described. The use of a Horner–Wadsworth

• –Emmons reaction as a key step for generating the β'-amino-α,β-enones, permits access to a range of substrates under mild conditions and in moderate to high yield. Keywords: β’-amino-α,β-unsaturated ketones; Horner–Wadsworth–Emmons reaction; stereoselective synthesis; Introduction Compounds

• devised for the asymmetric synthesis of β’-amino-protected-α,β enones, a valuable intermediate for the synthesis of trans 2,6-disubstituted piperidines. The scope and limitation of the aza-Michael reaction were studied with a range of substrates. We are currently working on the application of this

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• -metal salts of these betaine-like amides are able to form imines with enones, which are activated by Lewis acid interaction for nucleophilic attack by 4-hydroxycoumarin. The addition of 4-hydroxycoumarin to enones gives ee’s up to 83% and almost quantitative yields in many cases. This novel type of

• myriad of enantioselective transformations, e.g., with aromatic or aliphatic enones [1]. There are many approaches employing protonated derivatives of chinchona alkaloids [2][3][4][5], amino acid derivatives, and chiral 1,2-diamines, which provide excellent yields and enantioselectivities. Among the most

• % whereas the trans-diaminocyclohexane derivatives could only reach up to 47% ee (Table 1, entry 5). There is a strong preference for 7 to produce higher ee’s if cyclic enones are used, whereas diaminocyclohexane derivatives perform better with the acyclic trans-enone 9 (Table 1, entry 4 versus Table 2

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• have been performed in microflow systems. The first of these was an intermolecular reaction between enones and vinyl esters or ethers (Scheme 1). By using a 300 W Hg lamp and a FOTURAN glass reactor the reaction gave moderate to high yields, albeit with poor diastereoselectivity [23]. Subsequent work

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• explored by several groups [72][73]. In 2007, Jørgensen et al. reported that the organocatalyzed asymmetric aza-Michael addition of hydrazones to cyclic enones had been achieved in good yield and stereoselectivity [74]. In 2011, the Deng group developed a highly enantioselective organocatalytic synthesis

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• to 56%) and enantioselectivities in the range of 85–91% ee (Scheme 9). Mechanistically the reaction involves the iminium activation of the α,β-unsaturated cyclic enones by the chiral pyrrolidine catalyst. Very recently, Xu and co-workers [51] reported an improved protocol for the same reaction

• employing a chiral pyrrolidine bearing a 2-mercaptopyridine moiety as organocatalyst (VII) and simple α-amino acids, such as tert-leucine, as co-catalyst. The asymmetric transformation proceeds by simultaneous activation of cyclic enones 13 and aldehyde 1 by the bifunctional catalyst VII and the amino acid

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• calculated VCD spectra of the reaction product 3a. Keywords: Michael addition; non-covalent catalysis; organocatalysis; squaramide; thiourea; Introduction The asymmetric 1,4-conjugated addition (Michael reaction) of C-nucleophiles to enones is a powerful tool for obtaining a significant variety of

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• leaving group β-positioned to the keto group, thereby facilitating elimination to enones 17 (Scheme 5). In the case of compound 12, which predominantly exists in a form lacking the typical cyclized carbinolamide moiety, the C-9 keto group can preserve its electronic properties, thus facilitating the

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• novel concept combines the unique reactivity patterns of transition metal catalysis with fundamental organic reactivity, in a sequential or consecutive fashion. Over the years, we have contributed to this concept through Pd/Cu-catalyzed accesses to enones and ynones and the in situ transformation of

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

• product when treated with TA–Au catalyst, even after an extended reaction time (24 h). This was probably caused by the preferred 1,2-rearrangement with the formation of a vinyl–Au intermediate. The aliphatic propargyl esters (1g, 1h) also did not give any desired allene products (enones from hydrations

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• and enones, as well as in palladium-catalyzed allylic substitution reactions [14][15][16][17][18][19][20]. Thus, the synthesis of specifically functionalized pyridines is of considerable interest, and many approaches toward this heterocyclic structure have been disclosed in the literature [21]. In

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

• -methoxyphenylboronic acid or 1 equiv of methanol [52]. Mechanistically, it was proposed that the enones 103 were produced through two pathways (Scheme 19). The gold(I)-catalyzed rearrangement of propargylic tert-butyl carbonates gave diversely substituted 4-alkylidene-1,3-dioxolan-2-ones 115 [53]. For example

• ). Similar strategies [145][146] were applied to synthesize arylated (Z)-enones, -enals or dihydrocyclohepta[b]indole skeletons 277 by gold-catalyzed cascade Friedel–Crafts/furan (or indole)–alkyne cycloisomerizations (Scheme 48). The polysubstituted butenolides 281 could be obtained through a gold-catalyzed

• substituted naphthalenes 296 [151]. This cascade reaction involves a tandem sequence of 1,3- and 1,2-migration of two different migrating groups. Jin and Yamamoto prepared the fused tri- and tetracyclic enones 298 through an efficient gold(III)-catalyzed tandem reaction, heteroenyne metathesis, and Nazarov

Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

• Peter Wipf and
• Marija D. Manojlovic

Beilstein J. Org. Chem. 2011, 7, 824–830, doi:10.3762/bjoc.7.94

• to achieve the carbalumination of 1-alkynes [10], internal alkynes [11], conjugated enynes [12], and 1-iodoalkynes [13]. Huang and Pi found that allylzirconocenes underwent conjugated addition to enones in the presence of CuBr·SMe2 [14]. Wipf and Pierce demonstrated that, upon the addition of a zinc

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

• synthesis of both molecules. In addition, 3- and 1-substituted cyclopropyl propargylic acetates 98 and 99 have also been intensively studied and provide access to 5- and 6-membered ring enones, respectively (Scheme 29) [62][63][64]. In the former substrates, experimental as well as computational evidence

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• chemistry. This mini-review focuses on the most recent achievements on gold-catalyzed oxygen transfer reactions of tethered alkynones, diynes or alkynyl epoxides to cyclic enones. The corresponding mechanisms for the transformations are also discussed. Keywords: alkyne–carbonyl metathesis; cyclic enones

• conjugated enone substructure has attracted the interest of synthetic chemists for decades. Among numerous methodologies, aldol condensations and Wittig-type reactions have been widely utilized [9][10][11][12][13][14][15][16][17][18]. Recently, it was found that conjugated enones could be generated from the

• cyclic enones from alkynyl ketones Yamamoto and co-workers were the first to report the gold-catalyzed formation of conjugated cyclic enones under mild conditions using tethered alkynyl ketones as substrates (Scheme 2) [43]. Both, aromatic and aliphatic groups substituted on alkynyl ketones 1 were

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• demonstrated by the catalytic asymmetric additions of thiols to α,β-unsaturated ketones [44]. (R)-LaNa3tris(binaphthoxide) (LSB) catalyses asymmetric addition to cyclic enones (Scheme 16), and products of addition 43 are isolated in good yields and enantiomeric ratios. However, addition to the substituted

• thioether 29. Thioethers 33 prepared from phosphinites 31. Preparation of enantiomerically pure thiol 39. Thioethers prepared by a modified Mitsunobu reaction. Nucleophilic conjugate addition. Asymmetric addition to cyclic enones. Preparation of thioether 45. Catalytic kinetic resolution of the enantiomers

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• -alkynylanilines can be followed by 1,4-addition to enones [15][16], iodination [17] or reaction with 1,3-dicarbonyl compounds [18]. Perumal recently demonstrated that aldehydes and nitroalkenes can be used as electrophilic partners [19][20]. Triple bonds can also serve as a second electrophile for the

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

• allylic acetates [75][76], carbene-transfer reactions from ethyl diazoacetate [77], formation of conjugated enones and enals [78], regio- and stereoselective synthesis of fluoroalkenes [79], and so on [80][81][82][83][84][85]. However, reports on NHC–Au catalyzed asymmetric reactions are rare [86]. The

Synthesis of 2a,8b-Dihydrocyclobuta[a]naphthalene-3,4-diones

• Kerstin Schmidt and
• Paul Margaretha

Beilstein J. Org. Chem. 2010, 6, No. 76, doi:10.3762/bjoc.6.76

• (relatively) low yield of mixed cycloadduct formation from excited 1 and alkynes seems disappointing. Nevertheless, one should bear in mind that a) dimer formation on irradiation of phenyl-conjugated enones, e.g., 3-phenylcyclohex-2-enone, is not suppressed even in neat alkenes as solvent [6], as these

Efficient 1,4-addition of α-substituted fluoro(phenylsulfonyl)methane derivatives to α,β-unsaturated compounds

• G. K. Surya Prakash,
• Xiaoming Zhao,
• Sujith Chacko,
• Fang Wang,
• Habiba Vaghoo and
• George A. Olah

Beilstein J. Org. Chem. 2008, 4, No. 17, doi:10.3762/bjoc.4.17

• enones can be used to introduce difluoromethylene moiety while Kumadaki and coworkers [21][22] have used bromodifluoroacetate with a copper catalyst to introduce the CF2 functionality. There also exist few reports on the 1,4-addition of monofluoromethylene moieties to α,β-unsaturated compounds [23][24

Part 1. Reduction of S-alkyl- thionocarbonates and related compounds in the presence of trialkylboranes/air

• Jean Boivin and
• Van Tai Nguyen

Beilstein J. Org. Chem. 2007, 3, No. 45, doi:10.1186/1860-5397-3-45

• . Alternatively, radical C might fragment to conjugated enone E and stabilised TolSO2• radical. Neither compounds D nor enones E were ever isolated in the present work. Similarly, these compounds were not seen in a precedent work in which a "fast" hydrogen atom donor (hypophosphorus acid) or a "slow" hydrogen

Vinylogous Mukaiyama aldol reactions with 4-oxy-2-trimethylsilyloxypyrroles: relevance to castanospermine synthesis

• Roger Hunter,
• Sophie C. M. Rees-Jones and
• Hong Su

Beilstein J. Org. Chem. 2007, 3, No. 38, doi:10.1186/1860-5397-3-38

• reagent of choice for promoting extended (vinylogous) Mukaiyama addition reactions to aldehydes,[4] imines [5] and conjugatively to enones [6][7] under Lewis-acid mediated dissociative reaction conditions. Many of these reactions reveal high diastereoselectivities, which has been exploited to access a