Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• .10.44 Abstract The cyclocondensation of enones with aminoacetonitrile furnishes 3,4-dihydro-2H-pyrrole-2-carbonitriles which can be readily converted to 2,4-disubstituted pyrroles by microwave-induced dehydrocyanation. Alternatively, oxidation of the intermediates produces 3,5-disubstituted pyrrole-2

• the literature. They can be obtained from enones by Michael addition of nitromethane, partial reduction and dehydrogenation of the resulting pyrroline with selenium or sulfur in moderate yields (3 steps) [40][41]. Alternatively, a Nef reaction of the nitromethane adducts gives masked 1,4-dicarbonyls

• which can be cyclized to compounds 7 in yields of up to 50% (over 4 steps) [42]. Other methods involve the use of stoichiometric zirconocene dichloride [43], the reductive coupling of alkynes to enones followed by ozonolysis and Paal–Knorr cyclization [21] or the reaction of vinylazides with aldehydes

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• with various dipolarophiles, such as α,β-unsaturated esters [21][22][23][24][25], dienones [26][27], α,β-unsaturated ketones [28][29][30], unsaturated aryl ketones [31][32][33] and electron-poor alkenes [34][35][36][37][38][39]. Among the studied α,β-unsaturated enones for 1,3-dipolar cycloaddition

• -unsaturated enones. Moreover, we envisioned that the additive might effectively tune the regioselectivity of a 1,3-dipolar cycloaddition of azomethine ylide. Herein, we report a three-component 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from isatin derivatives and benzylamine, with

• nature of the substituent and its position on the benzylideneacetone aromatic ring significantly influenced the regioisomeric ratio. In general, the regioisomeric ratio with water as an additive is comparatively higher for the substrates in which the phenyl rings of enones were substituted by electron

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• Buchwald’s procedure for the catalytic asymmetric vinylation of enones [51]. However, the desired vinylated product could not be obtained under the described conditions. An alternative α-formylation/Wittig olefination sequence gave only low yields. O’Brien et al. [41] described the failure of a direct

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• Chemistry and Food Biotechnology, Heinrich-Buff-Ring 58, 35392 Gießen Department of Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany 10.3762/bjoc.9.262 Abstract Allylic oxidations of olefins to enones allow the efficient synthesis of value-added products from simple

• Pleurotus sapidus. This ‘’mushroom catalysis’’ is operationally simple and allows the conversion of various unsaturated spirocyclic terpenoids. A number of new spirocyclic enones have thus been obtained with good regio- and chemoselectivity and chiral separation protocols for enantiomeric mixtures have been

• developed. The oxidations follow a radical mechanism and the regioselectivity of the reaction is mainly determined by bond-dissociation energies of the available allylic CH-bonds and steric accessibility of the oxidation site. Keywords: allylic oxidation; CH-activation; chiral separation; enones; flavors

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• ketones by the use of shelf-stable electrophilic trifluoromethylating reagents, S-(trifluoromethyl)diphenylsulfonium salts and copper under mild conditions is described. A wide range of acyclic aryl–aryl–enones and aryl–alkyl–enones were converted into β-trifluoromethylated ketones in low to moderate

• of regioisomers (C2/C3 1.1:1) [22]. We disclose herein the regioselective 1,4-addition of the CF3 group into simple conjugated acyclic enones including chalcones using S-(trifluoromethyl)diphenylsulfonium salt 3 and a copper system in 11–37% yields (12 examples). Results and Discussion We initiated

Synthesis of enones, pyrazolines and pyrrolines with gem-difluoroalkyl side chains

• Assaad Nasr El Dine,
• Ali Khalaf,
• Danielle Grée,
• Olivier Tasseau,
• Fares Fares,
• Nada Jaber,
• Philippe Lesot,
• Ali Hachem and
• René Grée

Beilstein J. Org. Chem. 2013, 9, 1943–1948, doi:10.3762/bjoc.9.230

• -mediated isomerisation affords enones in fair yields with a gem-difluoroalkyl chain. These derivatives were used to prepare pyrazolines and pyrrolines with the desired gem-difluoroalkyl side chain by cyclocondensations in good yields and with excellent stereoselectivity. A one-pot process was also

• ][21][22]. The goal of the present work is to demonstrate that selected propargylic derivatives [23][24][25] can be employed for the preparation of enones with a gem-difluoroalkyl chain by using an isomerisation process (Scheme 1). These intermediates can be employed for the preparation of

• bearing a CF3 group on the triple bond could be isomerised to the corresponding enones. In that case, Et3N proved to be sufficient as a catalyst to perform this transformation [28]. The required starting propargylic alcohols were obtained by a reaction of the lithium salt of easily available gem-difluoro

Gold-catalyzed regioselective oxidation of propargylic carboxylates: a reliable access to α-carboxy-α,β-unsaturated ketones/aldehydes

• Kegong Ji,
• Jonathan Nelson and
• Liming Zhang

Beilstein J. Org. Chem. 2013, 9, 1925–1930, doi:10.3762/bjoc.9.227

• following observations and considerations: a) propargylic carboxylates of type 4a with an internal C–C triple bond typically undergo facile 3,3-rearrangements [26][27][28][29][30] instead of 1,2-acyloxy migrations. The former process would eventually lead to the formation of the enones 6 [31]. Due to

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