Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• phosphorus pentoxide directly before use, respectively. All imines were prepared from corresponding aldehydes and amines. Methyl acrylate was distilled directly before use. Other commercially available reagents were used without further purification. All experiments were carried out under an argon atmosphere

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• in high yield with high diastereo- and enantioselectivities. The reaction with methyl acrylate also proceeded in high yield with high enantioselectivity; however, in this case the exo/endo selectivity was moderate. Methyl vinyl ketone and methyl methacrylate reacted with 1a to afford the desired [3

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• product was obtained exclusively. Under optimized conditions, various acrylates and amides can be synthesized via C–H activation reactions (Figure 6). Methyl acrylate, which did not show good general reactivity with arylureas under previous conditions, could be coupled in excellent yields (5i, 5j, 5k). As

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• base to participate in the catalytic cycle. In 2015, we reported a novel asymmetric dual-reagent catalysis strategy based on these chiral phosphine catalysts [42], in which the zwitterion in situ generated from the chiral phosphine and methyl acrylate acted as an efficient catalyst for the asymmetric

• Mannich-type reaction. As an extension of this work, we then wondered if other electrophilic partners instead of methyl acrylate could be used to generate similar catalytically active species in situ. Also inspired by the Mitsunobu reaction [43], we reported herein the reaction of azodicarboxylates with 3

Self-assemblies of γ-CDs with pentablock copolymers PMA-PPO-PEO-PPO-PMA and endcapping via atom transfer radical polymerization of 2-methacryloyloxyethyl phosphorylcholine

• Jing Lin,
• Tao Kong,
• Lin Ye,
• Ai-ying Zhang and
• Zeng-guo Feng

Beilstein J. Org. Chem. 2015, 11, 2267–2277, doi:10.3762/bjoc.11.247

• a channel-like crystal structure. With an increase in the amount of γ-CDs added, they began to accommodate the poly(methyl acrylate) (PMA) segments dissociated from the core of the micelles. When more γ-CDs were threaded and slipped over the segments, the γ-CDs were randomly distributed along the

• compared with PPO or PMAA), respectively, these unmatched PRs possess the potential to be applied as dynamic-responsive materials, carriers for controlled drug release, biosensors and catalysts. Poly(methyl acrylate) (PMA) prepared via ATRP of methyl acrylate (MA) is a typical hydrophobic polymer with a

• Group Co., Ltd., China. The average molecular weight (Mn) is 4580 g/mol. Methyl acrylate (MA) was purchased from J&K Company, China, and was used after removal of inhibitors. Both 2-bromoisobutyryl bromide (BIBB) and N,N,N’,N”,N”-pentamethyldiethylenetriamine (PMDETA) were available from Sigma-Aldrich

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• ring [78]. When olefin 93, bearing a pyridine without any substituent at C2 or C6, was treated with methyl acrylate in the presence of G-HII catalyst no reaction took place and the starting material was fully recovered. By contrast, the presence of a chlorine substituent at C2 on the pyridyl ring

• ). Various substituents on the pyridyl ring such as halides, trifluoromethyl or triflate groups were found to be suitable basicity modulators and the alkenes containing the corresponding disubstituted pyridines were efficiently coupled to methyl acrylate by utilizing a CM reaction. In addition, steric

Ru complexes of Hoveyda–Grubbs type immobilized on lamellar zeolites: activity in olefin metathesis reactions

• Hynek Balcar,
• Naděžda Žilková,
• Martin Kubů,
• Michal Mazur,
• Zdeněk Bastl and
• Jiří Čejka

Beilstein J. Org. Chem. 2015, 11, 2087–2096, doi:10.3762/bjoc.11.225

• of 1,7-octadiene and (−)-β-citronellene; HGIIN+Cl− on SBA-15 (HGIIN+Cl−/SBA-15) was the most active (TON up to 16000 in RCM of citronellene). HGIIN+Cl−/SBA-15 proved its versatility in RCM, enyne metathesis, metathesis of methyl oleate, and cross-metathesis of electron deficient methyl acrylate with

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• Chemistry, Hlavova 2030, CZ-128 40 Prague, Czech Republic Faculty of Chemistry, University of Seville, E-41012 Seville, Spain 10.3762/bjoc.11.201 Abstract The cross metathesis of 1,2-epoxy-5-hexene (1) with methyl acrylate and acrylonitrile was investigated as an entry to the synthesis of polyfunctional

• cross metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy alcohol and an amino alcohol in high yields. Keywords: cross metathesis; epoxide; ruthenium catalysts; tandem reactions; Introduction Catalytic carbon–carbon

• involving the cross metathesis of a commercially available epoxide-containing olefin with methyl acrylate and acrylonitrile and their subsequent transformations leading to multifunctional building blocks are reported. Results and Discussion Cross metathesis reactions involving electron-deficient olefins are

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• system 234 (91%). Alternatively, a ROM–RCM–CM sequence was employed under similar reaction conditions in the presence of methyl acrylate (232) as a CM partner. The tandem metathesis product 233 was obtained in 68% yield along with the ROM–RCM product 234 in 18% yield (Scheme 47). Later, 7-azanorbornene

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• worse than nG-SIPr. As outlined in Table 2, all tested catalysts were similarly effective in CM of methyl undecenoate 12 with cis-1,4-diacetoxy-2-butene (13), but parent dichloro complexes provided smaller quantities of dimerization product of 12. In CM of 12 with electron deficient methyl acrylate 15

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• conditions. Methyl acrylate (1a) was chosen as a model substrate as it is highly reactive in standard Matsuda–Heck reactions. Therefore, a solution of 4-nitrobenzenediazonium tosylate (2a) in water was allowed to react with 1.2 equiv of methyl acrylate (1a) in the presence of 1 mol % Pd(OAc)2 at rt, at 75 °C

• (t, 2H), 3.75 (t, 2H), 2.11 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 165.6, 142.6, 138.5, 132.7, 129.0, 121.4, 118.5, 112.3, 61.3, 41.8, 31.1; HRMS m/z: calcd. for C13H12NO2Cl, 249.0551; found, 249.0548. Arylation of methyl acrylate (1a) with arenediazonium tosylate 2a. Arylation of alkenes with ADT

• . Arylation of methyl acrylate (1a) with arenediazonium tosylate 2a. Study of reaction conditions. Arylation of alkenes with arenediazonium tosylates in water under microwave heating. Supporting Information Supporting Information File 354: Additional experimental data. Acknowledgements This research was

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• two chiral centers, and that produced a mixture of diastereomers with potential challenges in the stereoselectivities. Reaction of methyl acrylate (1d) with 2a and PMHS in toluene at 25 °C gave two diastereomers which were detected by GC, however inseparable by column chromatography. Formation of the

• hydride-catalyzed reductive aldolization of acetophenone [19]. Therefore, tert-butyl acrylate (1d) was used to replace methyl acrylate, and several biphosphorous ligands were screened for improving the diastereoselectivity (Table 3). Diastereomers of 3da were separated, which were subjected to further

• diastereomers were then deduced by 1H NMR chemical shifts of CHCH3 or OCH3. As shown in Table 3, syn-3da was favored when tert-butyl acrylate was used to replace the methyl acrylate (Table 3, entry 8 vs Table 2, entry 1). Higher yields were obtained in the presence of biphosphorous ligands (Table 3, entries 2–8

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• complicated TLC results. A change of substrate (N-benzyl-protected isatin), catalyst (DMAP) or other solvents (THF, DCM, dioxane), gave no different result. However, remarkably, when the activated alkene was changed from acrylamide to methyl acrylate, formation of required aza-MBH product 5aa in high purity

• access to these adducts for the rapid development of other methodologies. Optimization of the conditions and parameters revealed DABCO as a superior catalyst (Table 2). The reduction in the loading of methyl acrylate and catalyst, or dilution of the solutions did not have any major effect on time or

• yield. Thus, DABCO (0.25 equiv) along with methyl acrylate (3 equiv) in acetonitrile as a solvent was identified as the best condition (Table 2, entry 9). Next, the reaction on different substrates was further explored. The protocol was found to work consistently, delivering the product with a short

Relay cross metathesis reactions of vinylphosphonates

• Raj K. Malla,
• Jeremy N. Ridenour and
• Christopher D. Spilling

Beilstein J. Org. Chem. 2014, 10, 1933–1941, doi:10.3762/bjoc.10.201

• substituted vinylphosphonates 12a or 12b in good yield. In contrast, when vinylphosphonate 12a was subjected to a cross metathesis reaction with methyl acrylate, the cross metathesis product 16a was formed in low yield (~11%) as part of a complex mixture. More highly substituted vinylphosphonates (5 and 19

• ) failed to react at all with methyl acrylate under similar conditions, even with higher catalyst loading and extended reaction times. Initially, the synthesis of the allyl vinylphosphonate esters was achieved using a transesterification reaction catalysed by tetra n-butylammonium iodide (TBAI) (Scheme 5

• - and diallyl vinylphosphonates 21a and 21b. The products were isolated by silica gel chromatography to give 27% yield of the mono-allyl and 36% yield of the diallyl phosphonate esters. With the mono- and diallyl vinylphosphonates in hand, the cross metathesis reactions with methyl acrylate (a type II

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• impact on polymer solubility, including the presence of amine-functional groups and allyl polymers with a –CH2-spacer between the polymer backbone and the side chain or group [85][91]. These have since been used more as a set of guidelines as opposed to a set of hard-and-fast rules; poly(methyl acrylate

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• inexpensive dehydroepiandrosterone (5) by the means of a copper-mediated C–H hydroxylation in the 12-position and a palladium-catalyzed coupling of methyl acrylate to an activated enol ether in the 17-position. In synthetic direction (Scheme 2), dehydroepiandrosterone (5) was protected as its

• -dimethylaminopyridine, pyridine, 25 °C; then KOAc, MeOH, 64 °C, 85% yield for the two steps) to give 8. Generation of an enol triflate from the carbonyl group in 8 (potassium hexamethyldisilazide, phenyl bis-triflimide, THF, −20 → −10 °C, 85% yield) set stage for a Heck-reaction with methyl acrylate (cat. Pd(OAc)2, cat

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• L-amicetal 4 [36]. Alternatively, we have used 2 as a substrate for a cross metathesis reaction with methyl acrylate under isomerization-free conditions to furnish enoate 5, which underwent cyclization to the lactone 6 after hydrogenation. Reduction of 6 with DIBAL-H eventually yields a protected L

• -amicetose 7 [35]. To avoid the last step of the sequence, we envisaged a cross metathesis with acroleine, rather than methyl acrylate, to give enal 8 which should undergo spontaneous lactol formation after hydrogenation and desilylation. However, compared to cross metathesis reactions with methyl acrylate

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• unsaturated polyester was cross-linked by a 1,3-dipolar cycloaddition with the received dinitrones 10a/b. The 1,3-dipolar cycloaddition led to a strong change of the mechanical properties which were investigated by rheological measurements. Nitrones derived from methyl acrylate (3a) and methyl crotonate (3b

• study the course of this cycloaddition the two low molecular model nitrones methyl 3-[benzylidene(oxido)amino]propanoate (3a) and methyl 3-[benzylidene(oxido)amino]butanoate (3b), were prepared from methyl acrylate (2a) and methyl crotonate (2b) with E-benzaldoxime (1) (Scheme 1), respectively. The

• . 1,3-dipolar cycloadditions of model nitrones with dimethyl itaconate confirmed the proposed mechanism of cross-linking. Experimental Materials Acryloyl chloride (97%), crotonic acid (98%), itaconic acid (IA, 97%), methyl acrylate (99%), methyl crotonate (98%), succinic acid (SA, 99%), p

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• ], phenylacetylene [73][74], and methyl acrylate [75]. Starting from these results, a MC approach to 1-(isoquinolin-1-yl)guanidines 55 was efficiently developed by a silver triflate-catalyzed three-component reaction of 2-alkynylbenzaldehydes 25, tosylhydrazide (41) and carbodiimides 54 (Scheme 29) [76]. The

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• . In the case of methyl acrylate or acrylonitrile, a mixture of cis diastereomers was obtained regioselectively at higher temperature, in a 1:1.6 to 1:1.8 ratio. By contrast, the [4 + 2]-cycloaddition proved to be completely regioselective when performed on the catechol derivative in the absence of

• dienophile used (Scheme 5) [39]. Finally, interesting results were reported with methyl acrylate and dienes derived from tartrate esters (9/1 de, 70% ee for the major isomer) (Scheme 6) [40]. In 2003, Hall and co-workers reported the application of electron-rich dienylboronates in one-pot tandem Diels–Alder

• -component adducts were isolated in good yields up to 92%. A single diastereomer was detected with maleimides; the diastereoselectivity being lower with methyl acrylate and vinyl oxazolidinone (Scheme 7). A one-pot, palladium-mediated cycloisomerization of ene-ynes 5 was applied to the synthesis of the

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• reaction of methyl acrylate with benzaldehyde the substituted triamide catalysts show a comparable or an even superior activity relative to the thiourea analogue. Recently, Gale et al. demonstrated that the same phosphoric triamides effectively act as anion transporters by hydrogen bonding [19]. These

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• , 43500 Semenyih, Selangor Darul Shsan, Malaysia 10.3762/bjoc.9.325 Abstract The palladium metal catalysed Heck reaction of 4-iodoanisole with styrene or methyl acrylate has been studied in a continuous plug flow reactor (PFR) using supercritical carbon dioxide (scCO2) as the solvent, with THF and

• the reaction with methyl acrylate the reactor was scaled from a 1.0 mm to 3.9 mm internal diameter and the conversion and turnover frequency determined. The results show that the Heck reaction can be effectively performed in scCO2 under continuous flow conditions with a palladium metal, phosphine-free

• eliminated the requirement of an inert atmosphere. Reactions between iodobenzene and methyl acrylate achieved 85% yield and 100% selectivity to trans-methyl cinnamate at 200 °C and 80 bar. The reaction system was then extended to acrylonitrile as the olefinic substituent, and achieved a yield of 66% and 70

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• steps from monoprotected dienediol 10 via cross metathesis with methyl acrylate (22) [47] using a comparatively low loading of phosphine-free catalyst A, followed by MOM protection and Stryker–Lipshutz reduction of 24. Notably the latter step proceeds significantly more efficient in a toluene/tert

Self-assembly of 2,3-dihydroxycholestane steroids into supramolecular organogels as a soft template for the in-situ generation of silicate nanomaterials

• Valeria C. Edelsztein,
• Andrea S. Mac Cormack,
• Matías Ciarlantini and
• Pablo H. Di Chenna

Beilstein J. Org. Chem. 2013, 9, 1826–1836, doi:10.3762/bjoc.9.213

• showing that, although spherical spaces cannot be defined, prediction is possible by selecting solvents with HSP inside the gelation zones. Figure 2 qualitative shows that there is a good correlation between the HSP and the gelated solvents, pyridine and methyl acrylate are the only solvents that visible

• gelled by steroid 1, styrene and methyl acrylate offer great potential in the preparation of mesoporous polymers. We are currently exploring these materials and their potential applications. Experimental Materials Cholesterol (94%) was purchased from Sigma-Aldrich. n-Hexane, ethyl acetate