Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• line. A very recent example of a highly diastereoselective Ugi-type MCR was reported by Rivera, Paixão and co-workers using a steroidal isocyanide [31]. As shown in Scheme 9, the procedure comprised the organocatalytic asymmetric synthesis of the chiral bifunctional substrate 30 bearing an masked

• organocatalytic multicomponent approaches [32] not only the chiral steroidal isocyanide but also the bifunctional component 30, used in enantiomerically enriched form, plays a crucial role in the high stereoselection. The mechanistic insights of this class of MCR were disclosed in the original publication [31

• ]. In short, the organocatalytic conjugated addition of benzoylacetonitrile to cinnamaldehyde generates the hemiacetal 30, which next initiates the multicomponent sequence upon condensation with the aniline and formation of the imine, eventually occurring as a stable cyclic aminal. The attack of the

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• polyfurfuryl alcohol-supported catalysts for applications in heterogeneous enamine catalysis. The utilization of the polymer-supported catalysts in both batch and continuous-flow organocatalytic procedures proved moderate catalytic efficacy and enantioselectivity, but excellent diastereoselectivity in the

• employ a three-component, diastereoselective variant of the Ugi reaction for the synthesis of a prolyl pseudo-peptide catalyst, which proved effective in an organocatalytic conjugate addition reaction [6]. Later, our groups developed an Ugi reaction-based multicomponent approach enabling the structure

• diversification of prolyl pseudo-peptide catalysts [7], which also proved great efficacy in organocatalytic asymmetric Michael reactions. As extension of this concept to the field of immobilized organocatalysts, we reported the use of the multicomponent approach for the synthesis of silica-grafted peptide

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• mechanochemical ball milling. The organocatalytic polymerization of trimethylene carbonate to form aliphatic polycarbonates was found to be more efficient when using a mechanical ball-milling reaction than a solution polymerization (Scheme 1). The detailed findings are disclosed in this article. Results and

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• acid catalysts for over three decades [15][16][17][18][19][20][21][22][23][24][25][26]. Comparatively, interest in the utilization of metal-free organocatalytic oxo-DA reactions began to grow only after Rawal’s group reported a ground-breaking contribution in using a diol molecule, TADDOL, as a

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• (−)-Isoguaiene was prepared from (S)-citronellal in only 9–10 steps with good overall yields. Either a trienyne or a dienediyne metathesis and highly diastereoselective organocatalytic Michael additions of aldehydes derived from (S)-citronellal served as the key transformations. Keywords: domino reactions

• were interested in developing an efficient synthetic access to 1 using a combined organocatalytic/metal-catalyzed strategy related to the one applied to the preparation of 2 [7][8]. Results and Discussion As illustrated in Scheme 1, two alternative routes were retrosynthetically devised, both of which

• feature a domino metathesis event and an organocatalytic Michael addition as the key steps. In closer analogy to our improved synthesis of clavukerin A (2) [8], a relay metathesis [9] of trienyne 3 was expected to lead to the hydroazulene 1 selectively. Trienyne 3 was envisioned to result from a

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• recycle catalysts. However, only a limited number of organocatalytic moieties and functional groups have been attached to CD scaffolds so far. Cinchona alkaloids are commonly used to catalyze a wide range of enantioselective reactions. Thus, in this study, we report the preparation of new α- and β-CD

• well-explored strategy [2] which can be used to prepare various types of CD derivatives. Several examples of modified-CD derivatives with a catalytic nucleophilic center have been reported in the area of organocatalytic asymmetric reactions [11]. Initially, Kanagaraj et al. [16] used per-6-amino-β-CD

• potential of asymmetric organocatalytic reactions using CD derivatives. However, a wide range of catalytic groups, especially cinchona alkaloids (Figure 2), have been used in organocatalysis with excellent results. These naturally occurring compounds and their derivatives are commonly applied in various

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• enantioenriched precursors (R)-56a and (R)-56i (Scheme 21) [61]. The addition of a cyclopropenyllithium to an aldehyde is arguably the most widely used method to access cyclopropenylcarbinols but Gevorgyan et al. disclosed an interesting organocatalytic route to cyclopropenylcarbinols possessing gem-diester

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• these established methods necessary. Examples from the past 15 years include transition metal-catalyzed transformations [21][22][23], solid-phase synthesis directed at combinatorial library design [24] and organocatalytic annellation reactions [25][26]. Sparked by our interest in the development and

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• rim have been successfully developed and used in chiral recognition. But their use in asymmetric organocatalysis hasn’t been reported. To explore the organocatalytic behaviors of inherently chiral calix[4]arenes modified at the lower rim, Li et al. reported the synthesis of N,O-type enantiomers based

• methyl ester 120 in four steps (Scheme 39) [73]. The organocatalytic properties of this inherently chiral calixarene Brønsted acid was firstly examined in the aza-Diels–Alder reaction of imines bearing electron-withdrawing or electron-donating substituents 122 with Danishefsky’s diene (123, Scheme 40

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• an enantioselective organocatalytic Mannich reaction between isatin-derived benzhydrylketimines 12 and trimethylsiloxyfuran 13 [38]. Using 10 mol % of another type of organocatalyst, such as chiral phosphoric acid 14, the process led at −40 °C in THF to the corresponding butenolides 11 in moderate to

• first asymmetric organocatalytic synthesis of chiral 3-amino-2-oxindoles based on enantioselective aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines 3 with activated nitroolefins 39 [62]. The best results were achieved by using cinchona alkaloid-derived thiourea catalyst 40 in toluene at −10 °C

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• of ketone enolates to give 1,4-dicarbonyl compounds [26]. However, the radical-based method of Baran and the umpolung method of Maulide both take advantage of the selective activation of an amide and are therefore not amenable to ketone enolates. MacMillan reported the organocatalytic oxidative

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• small heterocycles, such as pyridine, can increase the rate of the reaction [60]. Most probably, this effect was organocatalytic in nature, being caused by a pyridinium species that forms in the reaction medium, an effect known from the acceleration of DCC-induced acylation reactions with

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide

• . Stereoselective Michael addition, one of the most important organocatalytic reactions [8] usually serves as a key stereoinduction transformation. Earlier studies, performed by Hayashi and Wang employed iminium activation to perform the enantioselective addition of nitromethane to enals for syntheses of baclofen

• ][21]. Other green chemistry concepts such as reusable media [22], immobilized catalysts [23], or flow set-ups have also been used with success for the synthesis of GABA derivatives [24]. Pregabalin is currently manufactured using enzymatic kinetic resolution [25], but an organocatalytic procedure

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• bond donor were developed and evaluated for enantioselective organocatalytic alcoholysis of meso-cyclic anhydrides. These structural diversified organocatalysts were found to induce high enantioselectivity in alcoholysis of anhydrides and was successfully applied to the asymmetric synthesis of (S

• chloramphenicol-derived bifunctional amide organocatalysts and their application for enantioselective alcoholysis of meso-cyclic anhydrides. In the precedented urea- or thiourea-based organocatalytic methanolysis of anhydrides, one big problem is the homo-aggregation of the catalysts via hydrogen bonding, which

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• –S bonds were developed and already excellently reviewed, including nucleophilic substitution reactions between S-nucleophiles and organic electrophiles, metal-catalyzed C–S bond formations and organocatalytic or enzymatic approaches [15][16][18][20][21][22]. This review provides a brief overview

• steric effects. In 2017, the group of Kokotos described a organocatalytic photoinitiated thiol–ene coupling reaction, applying phenylglyoxylic acid as photoorganocatalyst (Scheme 10) [40]. They have shown that the reaction mainly proceeds via a radical chain propagation mechanism, which is initiated by

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• -catalyzed oxidative deformylation of 1,2-amino alcohols is reported. A wide range of readily accessible amino alcohols and primary amines can be reacted to provide N-protected imine products. The methodology presented provides a novel organocatalytic approach for imine synthesis and demonstrates the

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• (Figure 1). These compounds are unique heterocyclic conjugated trifluoromethylketimines with two competing electrophilic centers which can enable either Michael- or Mannich-type nucleophilic additions. As found in our previous studies, organocatalytic addition of acetone [37], nitromethane [38] and

• screened organic base catalysts, solvents and temperature in the decarboxylative addition of malonic acid (nucleophilic component) to 1-methyl-4-trifluoromethylpyrimidin-2(1H)-one (2a, the simplest model substrate) aiming to find the optimal organocatalytic reaction conditions (Table 1). In the preliminary

• derivatives 10c and 11c by using the general procedure for N1(3)-PMB cleavage (see Scheme 1). Conclusion In conclusion, it has been demonstrated that the efficient and highly regioselective organocatalytic decarboxylative addition of malonic acid or its derivatives to 4-trifluoromethylpyrimidin-2(1H)-ones 2

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• ; MacMillan catalyst; organocatalysis; Introduction Organocatalytic iminium and enamine activation has attracted organic chemists for more than one century [1]. Until today a wide and constantly increasing number of different organocatalytic transformations with various substrates have been accomplished [2

• (OTf)3 in THF. This Lewis acid proved to be the Lewis acid of choice since the reaction proceeds without loss of optical purity [30]. The naphthyl residue was chosen since it revealed a high selectivity in the desired organocatalytic transformation. Table 1 depicts the scope with respect to 1-naphthyl

• esters, gave rise to the desired imidazolidinones 7f and 7g (Table 1, entries 5 and 6) in 46% and 32%, respectively. After evaluating the scope of imidazolidinones 7 we were keen to investigate which sterically more demanding aldehydes could be employed. Since the anticipated organocatalytic

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• K2CO3 (Scheme 3). Michael adducts were isolated with good to excellent yield (76–99%) in a high-speed vibration mill (HSVM) within 10–60 min [51]. Bolm and co-workers reported an organocatalytic asymmetric version of Michael addition reaction under planetary-milling (PM) conditions. Differently

• -(S)-proline derived catalyst [49]. b) Report using α,α-dipeptide-based catalyst [50]. Mechanochemical Michael reaction [51]. Mechanochemical organocatalytic asymmetric Michael reaction [52]. Mechanochemical Morita–Baylis–Hillman (MBH) reaction [53]. Mechanochemical Wittig reactions [55

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• utilise readily available starting materials and operate under mild organocatalytic conditions. Results and Discussion We initiated our study with readily available alkyne 4a and subjected it to reaction conditions similar to those we have previously reported (Table 1). By using 2-iodoanisole as

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• reactions of prochiral nucleophiles have been much less commonly reported than fluorination and chlorination reactions [49][50][51][52][53][54] and only a few reasonably enantioselective organocatalytic approaches have been reported so far [54][95][96]. In these few reports it became obvious that it is a

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• report, which is in line with our continuous interest in developing new sustainable organocatalytic protocols [39][49][50][51], and taking advantage of previous experience with the enzymatic hydrolysis of a racemic mixture of N-protected-β3-amino acid methyl esters [52], we decided to examine the use of

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• at times lead to complete aromatization of the moiety based on the dehydrogenation capability of the oxidant as well as the presence of the appropriate acidic protons in the heterocyclic substrate (path b', Scheme 1). To attend greener synthesis metal catalyzed and organocatalytic aerobic oxidative

• ) [83]. In general, electron-donating and neutral functionality (R = OMe, H) on the tetrahydroisoquinolines were well tolerated. Interestingly the electron-withdrawing groups were conspicuous by their absence. Metal-catalyzed aerobic dehydrogenation From organocatalytic aerobic dehydrogenation, in this

• conditions were not well tolerated by few sensitive groups, most of the β-carbolines were successfully prepared utilizing this procedure, including the alkaloid harmine with 99% yield. The final product precipitates at the end of the reaction and hence required minimum purification. Organocatalytic aerobic

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• transition state. Several successful results and a recent trend in organocatalytic atroposelective reactions, including enantioselective formation of chiral axes [17][18][19][20][21][22][23][24], dynamic kinetic resolution [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], kinetic

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• demand and potential for the development of a green one-pot cascade aldol/cyclization strategy for these compounds [22]. The use of β-keto acids as ketone enolate equivalents in metal- and organocatalytic decarboxylative aldol reactions has been extensively studied and proven to be a valuable and