Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• chiral calcium alkoxide complex was generated in situ by mixing Ca(OEt)2, PyBox ligand (S,S)-88, and phenol 89. The authors found that the slow addition of malonate 86 and the use of phenol 89 and ethanol as additives were all crucial for achieving high yield and enantioselectivity, although the exact

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• alkoxide species C. Reductive elimination of species C gave the product and regenerated the active iridium catalyst. Recently, Qiu and co-workers developed a novel chiral ligand L5 based on a chiral-bridged biphenyl backbone and successfully achieved the asymmetric addition of arylboronic acids to N

• ] and PCy3 formed the ruthenium(0) complex, which then mediated the oxidative coupling of N-benzyl-protected isatin and styrene to form oxametallacycle I. The ruthenium alkoxide III was formed through two possible pathways: (a) the direct transfer hydrogenolytic cleavage of I (slow); (b) the

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• control with electrophilic quench by a variety of electrophiles. After evaluating a few chiral diamino-alkoxide ligands, ligand 24 was identified as a superior choice. As shown in Figure 7, the result was not optimal with only 30–75% of the desired α-substituted products being obtained and the

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• anion equivalent 3 is known as the "Breslow intermediate". Its reaction with another molecule of aldehyde leads to the formation of an alkoxide intermediate 4. Proton transfer and subsequent release of thiazolylidene 1 affords the final product, the α-hydroxy ketone 5. Breslow demonstrated that

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• intermediate mechanism is usually involved. The formation of an inclusion-complex first occurs and then the secondary alkoxide of the host pseudo-intramolecularly attacks the phosphorus atom to form a covalent bond. Finally an alkoxide ion could react with the formed phosphonates to regenerate the CD secondary

• alkoxide and to release the hydrolyzed product (Scheme 2). In 1970, van Hooidonk and Breebaart first studied the alkaline hydrolysis of the enantiomers of isopropyl methylphosphonofluoridate (sarin) with α-CD in aqueous solution at pH 9.0 and 25 °C. A hydrolysis rate enhancement is observed and they report

Polydisperse methyl β-cyclodextrin–epichlorohydrin polymers: variable contact time ¹³C CP-MAS solid-state NMR characterization

• Isabelle Mallard,
• Davy Baudelet,
• Franca Castiglione,
• Monica Ferro,
• Walter Panzeri,
• Enzio Ragg and
• Andrea Mele

Beilstein J. Org. Chem. 2015, 11, 2785–2794, doi:10.3762/bjoc.11.299

• conditions to achieve deprotonation of the hydroxyl groups. Then, EP reacts with the alkoxide to form intra- or inter-ether linkages. We previously proposed the synthesis [22] of soluble and insoluble polymers of a partially secondary rim methylated β-CD (DS = 4.9) commonly called CRYSMEB. In this previous

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• 1. A catalytic amount of copper was enough to complete the reactions. In the synthesis of trifluoromethylarenes (Ar–CF3), the cross-coupling proceeded via the pathway shown in Scheme 17 [53]. First, the fluoride-ion-induced reaction of hemiaminal 1 with CuI-diamine complex 2 gave copper alkoxide 3

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• formaldehyde (in the case of reaction performed in MeOH), are consistent with the previously reported pathway (Scheme 2) [16]. In this mechanism initial substitution of a Cl− ligand in Cp by the solvent gives rise to the alkoxide complex A. Subsequently, the η5-Cp ring can undergo slippage to form complex B

• , with an η1-Cp ligand. The η1-Cp ligand is nucleophilic and can abstract a β-hydrogen from the alkoxide ligand to generate a Pd(0) species with a coordinated cyclopentadiene ligand (C). In this step the formaldehyde or acetone byproduct originating from the solvent is released. Finally, dissociation of

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• -6-(2-nitrophenyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine was determined by single crystal X-ray diffraction. Keywords: four-component; one-pot; pyrazolo[3,4-d]pyrimidine; sodium alkoxide; Introduction Heterocycles containing a pyrimidine ring are extensively present in natural products and are very

• could promote the reaction to produce 5a, though DBU needed a higher reaction temperature (Table 1, entries 4–6). Taking into account the yield of the reaction, sodium alkoxide was the best choice. The reaction performed in alcohol resulted in the highest yield (Table 1, entries 6–9). The reaction

• temperature was screened and the appropriate temperature was found to be 60 °C (Table 1, entries 6, 10 and 11). The amount of catalyst had an effect on the reaction and 1.2 equivalents of sodium alkoxide was the most appropriate choice (Table 1, entries 12 and 13). This means that sodium alkoxide is not only

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• higher temperatures. TMSCl is assumed to abstract an alkoxide group and to deliver at the same time the chloride as the preferred counterion for the imidazolium salts. As said, temperature plays a decisive role in the formation of stage d, requiring the N,N’-diarylbenzene-1,2-diamines to be heated in

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• calculations to elucidate the reaction step of CO2 insertion into cobalt(III)–alkoxide bonds, which is also the central step of metal catalysed carboxylation reactions. It was found that CO2 insertion into the cobalt(III)–alkoxide bond of [(2-hydroxyethoxy)CoIII(salen)(L)] complexes (salen = N,N”-bis

• , a linear Brønsted–Evans–Polanyi relationship was found between the activation energy and the reaction energy. Keywords: activation; alkoxide; carbon dioxide; cobalt; insertion; salen; Introduction Carbon dioxide (CO2) has been known to be an attractive carbon source for decades [1][2][3][4][5][6

• carbonates. In consequence, industrially relevant catalysts, combined with efficient processes, have only recently emerged for the manufacture of alternating polycarbonates [10] and polyethercarbonates [11]. The respective research has mainly focussed on homogeneous zinc–alkoxide complexes [12] and chromium

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• cannot exclude the possibility that this rearrangement occurs already on the Grignard reagent and that the actual nucleophile is allenemagnesium bromide [56][57]. Nevertheless, it is reasonable to assume that prior to its acidic work-up 5h contains an intramolecular alkoxide function that may certainly

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• , amides, aldehyde, and ketone upon treatment with hydroxide, alkoxide, amine, diisobutylaluminium hydride and Grignard reagent, respectively. In these transformations, N-methyl-N-tosylcarboxamides behave like a Weinreb amide. Similarly, N-methyl-5-phenylisoxazole-3-carboxamide was converted into 3

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• ). After exiting the cold reactor zone, this stream passes through a coil maintained at 30 °C in order to ensure the complete consumption of the ketone 134. The resulting solution of lithium alkoxide 135 is combined with a further stream containing trifluoroacetic anhydride (TFAA) before being mixed with a

Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

• Antonio Monopoli,
• Pietro Cotugno,
• Carlo G. Zambonin,
• Francesco Ciminale and
• Angelo Nacci

Beilstein J. Org. Chem. 2015, 11, 994–999, doi:10.3762/bjoc.11.111

• methylene deprotonation, the alkoxide anion (RO−), can in fact originate (in situ) from the degradation of the allylic carbonate by the Pd catalyst [2]. Optimisation of the reaction conditions was carried out on the model substrate diethyl malonate by varying several parameters such as ligands, Pd sources

CO₂ Chemistry

• Thomas E. Müller and
• Walter Leitner

Beilstein J. Org. Chem. 2015, 11, 675–677, doi:10.3762/bjoc.11.76

• ]. Activation of carbon dioxide by inserting it into metal-alkoxide bonds allows for subsequent applications in polymer synthesis such as the copolymerisation of carbon dioxide with epoxides and other co-monomers [11]. Here, the catalysis with cobalt complexes still presents surprising effects [12]. More

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• ). Interestingly, when the oxygen in (S,S)-(+)-pseudoephedrine was protected, a reversal in diastereoselectivity was observed [54]. The authors attributed the difference in diastereoselectivity to the fact that when unmodified (S,S)-(+)-pseudoephedrine is used, a lithium alkoxide is produced in the presence of the

• lithium amide nucleophile. This alkoxide is believed to direct the addition of the lithium amide through coordination (Figure 4). On the other hand, when the oxygen in pseudoephedrine is TBS-protected (OTBS-15), this group sterically blocks one side of the double bond, thus the nucleophile attacks the

• method to synthesize protected syn-1,3-diols by performing intramolecular conjugate additions to a series of α,β-unsaturated esters and amides [71] (Scheme 8). Upon treatment of 24 with KHMDS and benzyaldehyde, a hemiacetal forms which provides the alkoxide nucleophile for the DCA reaction. These

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• either the rac or meso diastereomer could be realised. The meso enriched diastereomer of 8a could be realised by treating rac/meso mixtures of bis-lithium alkoxide of 8a with freshly prepared anhydrous NBu4F (2 equivalents) [23] (Scheme 3). Acid quench of the resultant purple dianion leads to ca. 5:1

Switching the reaction pathways of electrochemically generated β-haloalkoxysulfonium ions – synthesis of halohydrins and epoxides

• Akihiro Shimizu,
• Ryutaro Hayashi,
• Yosuke Ashikari,
• Toshiki Nokami and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2015, 11, 242–248, doi:10.3762/bjoc.11.27

• alkoxide ion, which is protonated by water to give bromohydrin 5a-Br (Scheme 2). The stereochemistry determined by NMR (5a-Br was synthesized using NBS according to the literature; see Supporting Information File 1) indicated that the addition of Br+ and DMSO across the C–C double bond was anti-selective

• , which is consistent with the results reported previously [22]. Treatment of 3a-Br with NaOMe resulted in a different product, namely epoxide 6a in 95% yield. In this case, the methoxide ion attacks the sulfur atom and cleaves the S–O bond under formation of an alkoxide ion. The latter intramolecularly

• attacks the carbon atom bearing the bromine substituent to give epoxide 6a (Scheme 2). Presumably, the protonation of the alkoxide ion with MeOH is slower than the intramolecular nucleophilic attack. We could not exclude the possibility that a protonated DMSO molecule presumably generated by the reaction

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

• conjugate reduction of the α,β-unsaturated diester with newly generated copper hydride, followed by aldol reaction to yield the key intermediate alkoxide A, which is subjected to further lactonization to form the lactone. Lam’s group has furnished a cobalt-catalyzed conjugate reductive aldolization

• with a γ-keto ester (instead of simple ketone) would yield an intermediate B as described in Figure 2. Intermediate B possesses a γ-alkoxide unit and an ester unit as that in intermediate A, and therefore, it is expected to afford a γ-carboxymethyl lactone as the final product. Furthermore, change of

• condensation [20]. Therefore, it is rationalized that an α,β-unsaturated monoester-derived enolate should react preferentially with the keto group in the keto ester to yield the alkoxide, which further lactonizes with an intramolecular ester group to form the lactone. It should provide a novel three-step

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• opening and generation of the benzimidazolium N-ylide 7 by the action of the alkoxide. The benzimidazolium N-ylide 7 reacts with the activated alkynes 3 to give the corresponding primary cycloadduct dihydropyrrolo[1,2-a]benzimidazoles 8. The formation of pyrrolo[1,2-a]quinoxalin-4-ones 4 involves the

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• unambiguously confirmed by single-crystal X-ray analysis. The formation of o-tolyl isomers 4 and 5 can be explained by the possible reaction sequence (path 1) depicted in Scheme 2. The first step involves an addition of the Grignard reagent to the saccharide aldehyde, producing a trienic magnesium alkoxide

• ][25] for the reaction of 1-naphthylmethylmagnesium chloride (10) with some aldehydes and ketones (Scheme 3). However, in this case, a trienic magnesium alkoxide intermediate E (magnesium salt of 2-hydroxymethyl-1-methylene-1,2-dihydronaphthalene, an analogue of intermediate A in Scheme 2, path 1

• ), produced by an addition of the Grignard reagent 10 to the monomeric formaldehyde (11, R1 = R2 = H), was unstable and decomposed by a reversible process into the Grignard reagent and aldehyde. The latter underwent a Prins-type reaction with the magnesium alkoxide intermediate E in the presence of MgCl2, to

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• , entry 16), indicating the potential use of this reagent as a tosylating agent for phenols. The outcome in the phenol reaction may be linked to the potential reaction pathway, an aspect that is described below. However, because phenoxide is a softer nucleophile as compared to alkoxide, we had to consider

Copolymerization and terpolymerization of carbon dioxide/propylene oxide/phthalic anhydride using a (salen)Co(III) complex tethering four quaternary ammonium salts

• Jong Yeob Jeon,
• Seong Chan Eo,
• Jobi Kodiyan Varghese and
• Bun Yeoul Lee

Beilstein J. Org. Chem. 2014, 10, 1787–1795, doi:10.3762/bjoc.10.187

• signals were observed at 25 °C and ca. 70 °C (entries 1, 5, 8–10). In the polymerization reaction, the nitrate and acetate anions in 1 became chain-growing carbonate or alkoxide anions [14][17]. In the presence of protic compounds such as water (present as an impurity) or alcohols (deliberately added

• incorporation process in the PO/CO2/PA terpolymerizations. In addition to the direct attack of the alkoxide anion on PA, another PA consumption process might operate in the presence of the chain transfer agent such as deliberated added ethanol or impurity water. In this process, PA directly reacted with the

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• complex 1. The reaction begins with the addition of NH3 to the carbonyl carbon of acetaldehyde to form a Mulliken charge-transfer complex 2. This complex was firstly proposed here. In 2, the C–O bond is elongated to1.345 Å, which has an alkoxide character and the complex is not stable in the gas phase

• . However, it is more stable than the precursor complex by 3.5 kcal/mol when ten specific water molecules are considered; see Figure 2. This result indicates that the consideration of water molecules in the reaction is necessary to describe the step 1 → 2. Then, the alkoxide oxygen atom captures a proton