Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• . Challenges: Gas formation from amine deprotonation, residence time optimization due to variations in the amine and amide properties. System setup: The same flow system was used as for the generation of turbo Grignard reagents (Figure S2, Supporting Information File 1). For TMPH, a coil (V = 10 mL, ID = 0.03

• ″) for the tert-amyl alcohol addition (Figure S4, Supporting Information File 1). Finally, we explored the formation of sterically hindered oxygen bases by a direct alcohol deprotonation. Knochel-type tert-amyl magnesium alkoxide (t-AmylOMgCl⋅LiCl) 1.0 M (95%) was obtained (≈15 mL) by the reaction of the

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• between the aryl substrates 30.1 and the amides 30.2 for the synthesis of the Weinreb amides 30.3 using DCA (OD5) as an organic dye. Under visible-light irradiation, the SET oxidation of 30.2 by the excited state of DCA, followed by a deprotonation, afforded the amidyl radical. This radical behaved as a

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• ion, then giving an imine after deprotonation (Scheme 50). Adopting this strategy, Che and co-workers obtained several imines in 90–99% yield from secondary amines [102] (Scheme 51). The authors observed that the oxidation is regioselective, occurring at the less substituted position of nonsymmetric

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• a certain extent Hg2+) initially induced a ring-opening reaction that was irreversibly followed by a fast ring closure–deprotonation–oxidation sequence to give styryl-substituted naphthoxazole derivatives as the products quantitatively. For the quinolizinium-substituted spirooxazine derivative, the

• short-lived absorption band between 500 and 650 nm, which supports this hypothesis and suggests that the processes have different rate constants in the presence of Cu2+ or Fe3+. We finally propose that the following reaction steps, i.e., the ring closure, deprotonation, and electron transfer to a second

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• (Scheme 27b). The sulfate radical then reacted with formamide (106) to produce the carbamoyl radical 125, which could perform a nucleophilic addition to the C-2 position of the protonated benzothiazole 126. A deprotonation, followed by an oxidation, most probably by the intermediates 121 and 122, could

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• the isomerization of 3-phospholene oxides 1 under basic conditions The calculations showed that the reaction mechanism follows a simple sequence under basic conditions (Scheme 4). In the first step the base makes the reactant–base complex 20, and the consequent deprotonation occurs at position C(2

• hypersurface (PES)). Triethylamine can initiate the deprotonation, but the reaction enthalpy towards 21 is very endothermic, making the reaction rate negligible, as observed in the experiment. In the case of KCO3− (instead of Cs2CO3), the deprotonation proceeds smoothly with almost a thermoneutral fashion

• deprotonation by NaOEt is already a slightly exothermic process, suggesting a fast transformation. Conclusion In this comprehensive study, the isomerization of 3-phospholene oxides 1 to the corresponding 2-phospholene oxides 4 was investigated. Complete isomerization took place either in the presence of

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• results, a reaction mechanism was therefore postulated in Scheme 3. Deprotonation of the α-carbon next to the carbonyl group generates a carbanion 8, which then undergoes a nucleophilic attack to the carbonyl carbon of the ester to give a cyclic enol 9. Leaving of the ethoxy group forms the 2,4-dione

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• intermediate A, followed by oxidation with (NH4)2S2O8, gave intermediate C [21][42][43][44][45][46][47]. Finally, deprotonation of intermediate C (R2 ≠ H) with NaHCO3 delivered the aromatized product 4. In the case of intermediate C (R2 = H), intermediate D was probably formed, and further underwent

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• for ricin toxin A (RTA) inhibitors [14]. By deprotonation of the lactam NH, and conversion to the DBU salt, the pterin easily dissolves in methanol at high concentrations, unprecedented for unfunctionalized pterins. This greatly accelerated the development of a library of bioactive pterins, as it

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• provide a transient radical, which undergoes an intramolecular cyclization to give the aryl radical anion. A final oxidation/deprotonation sequence delivers the product. In 2018, Reiser and co-workers reported the use of the [Cu(dap)2]Cl catalyst in the oxoazidation of styrene derivatives (Scheme 14) [30

• from the oxidation of the amine with the formed [Cu(II)] complex, followed by a deprotonation by DABCO. The resulting alkoxide is finally converted into the alcohol by the protonated DABCO. During this study, the authors found that replacement of the base by the Brønsted acid (R)-1,1-binaphtyl-2,2-diyl

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• hydrazine on the more reactive carbon atom of the fluoroenolate in a Michael-type addition. The cyclization did not require a deprotonation of the RNH moiety. Conclusion In summary, a synthesis of fluorinated pyrimidines under mild conditions using fluoroenolate 8 and amidines in a cyclocondensation was

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• their corresponding phenoxasilin derivatives 3b and 3c in 66 and 74% yield, respectively. The yields of 3b and 3c were improved to 83 and 91% in the presence of a catalytic amount of 2,6-lutidine, probably due to the acceleration of the deprotonation step by 2,6-lutidine [33]. In the case of

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• ). Therefore, we focused on methods to trap the HCl from solution (see Table 2). An addition of 2,6-lutidine as a base leads to a lower conversion. Although the addition of a base is an efficient method to remove HCl, deprotonation of monochloroacetic acid leads to an anionic species that is harder to reduce

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• proposed mechanisms for direct arylation (Scheme 2). Amongst these mechanisms, the most widely accepted is the concerted metalation–deprotonation (CMD) pathway [21]. Within the indole direct-arylation literature, however, there remains much discussion of an electrophilic metalation mechanism, with the

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• suitable bases. The metalation reaction is prone to side reactions when carried out at higher temperatures and as such, the reaction must be carried out below 0 °C. For example, pyridyllithium derivatives as intermediates can be subjected to deprotonation, substrate addition and pyridine formation due to

• chloropyridylphosphine 14 with PhPLi2. In a similar manner, the hexadentate pyridylphosphine 16 was synthesized: Firstly, PhPH2 was treated with an equivalent amount of n-BuLi to afford LiPHPh. The latter was then reacted with 14, followed by deprotonation with n-BuLi and reaction with 0.5 equiv CH2Br2 to afford

Oligomeric ricinoleic acid preparation promoted by an efficient and recoverable Brønsted acidic ionic liquid

• Fei You,
• Xing He,
• Song Gao,
• Hong-Ru Li and
• Liang-Nian He

Beilstein J. Org. Chem. 2020, 16, 351–361, doi:10.3762/bjoc.16.34

• the cation of IL and attacks the intermediate A (step I), generating a tetrahedral intermediate B. Finally, dehydration and deprotonation of the tetrahedral intermediate occurs (step II), forming dimeric ricinoleic acid C. The carboxyl and hydroxy groups in the dimeric ricinoleic acid may further

Formal preparation of regioregular and alternating thiophene–thiophene copolymers bearing different substituents

• Atsunori Mori,
• Keisuke Fujita,
• Chihiro Kubota,
• Toyoko Suzuki,
• Kentaro Okano,
• Takuya Matsumoto,
• Takashi Nishino and
• Masaki Horie

Beilstein J. Org. Chem. 2020, 16, 317–324, doi:10.3762/bjoc.16.31

• shown to proceed in a dehalogenative manner [3]. We have recently shown that the generation of the organometallic monomer species can alternatively also be achieved by deprotonation, using 2-halo-3-substituted thiophene 2 or 3 with a bulky magnesium amide Knochel–Hauser base (TMPMgCl⋅LiCl) [7], followed

• coupling is followed by chlorination, this protocol exploits the improved deprotonation efficiency of 2 toward 3’-unsubstituted 3-substituted bithiophene, and this method enabled the synthesis of 4 (where R1 = H) regioselectively. Polymerization of 4 (where R1 = n-hexyl and R2 = (CH2)4Si(Me2)OSiMe3) was

• with monomer precursors 4 by deprotonation with Knochel–Hauser base followed by the addition of the nickel catalyst NiCl2(PPh3)IPr to initiate the polymerization of bithiophene. We first carried out the polymerization of chlorobithiophene 4a, bearing hexyl and methyl substituents at the 3- and 3

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• seen in Figure 8, the mechanism of the reaction commences with the deprotonation of the biphenyl carboxylic acid 36, followed by the reaction of 38 with dimethyl dicarbonate (DMDC) to generate compound 39. On the other hand, the photocatalyst is excited by metal–ligand charge transfer, which produces

• an intermediate radical anion 40 via SET. Then, the intermediate 40 yields the acylated radical 41 by fragmentation, which, upon intramolecular addition, followed by one-electron oxidation and deprotonation, gives the desired product 37. C–H thiolation Synthesis of benzothiazoles via aerobic C–H

• triflyl chloride (64) by SET gives the highly energetic compound 66, which combines with 88 to give 94. The oxidation of 94 by 92 generates an intermediate 95, which, upon further deprotonation, produces the desired product 89 (Figure 14). C–H lactonization: synthesis of benzo-3,4-coumarins Benzo-3,4

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• deprotonation of the hydroxy group, and that the lack of observable photoswitchability arose due to fast free rotation around the C–C single bond connecting the thioindigo and hemistilbene motifs. Interestingly, in neutral or acidic aqueous media where the quinoidal structure is not present (λmax ca. 370, 480

Terpenes

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 2966–2967, doi:10.3762/bjoc.15.292

• generate a highly reactive cationic intermediate that can be subject to a cascade reaction through typical carbocation chemistry, including cyclisation reactions, hydride migrations and Wagner–Meerwein rearrangements [1][2]. The cascade is usually terminated by deprotonation or attack of water. The

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• rearrangement; silyl ketene acetals; Introduction The Ireland–Claisen rearrangement is a reaction converting allyl esters to γ,δ-unsaturated carboxylic acids. Its key step is a [3,3]-sigmatropic rearrangement of a silyl ketene acetal, which is generated in situ by deprotonation of an allyl ester using a strong

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• NMR spectroscopy. The mechanism by which IPA facilitates the reaction towards the formation of the cyclic hemiketal and indeed, the desired β-ketonitrile scaffold, has not been conclusively determined in this work. It is well known that strong-base deprotonation of acetonitrile leads to the formation

• solvent is effectively lowered by adding a small amount of polar, protic IPA and this facilitates acetonitrile deprotonation. Alternatively, the addition of a crown ether is also known to enhance nucleophilic substitution reaction rates, but in this case through the suppression of ion-pairing [16]. We

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• electrostatic interactions [54]. Moreover, TCs also assist intramolecular atom transfer and rearrangements including hydride or proton transfer and carbon shifts [10]. Eventually, the carbocation is quenched by deprotonation (E1-like) or nucleophilic attack (SN1-like) of water [45]. In contrast to

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• to 2-acylimidazole derivatives 94 generates the Lewis acid/enolate complex 100 upon deprotonation (Scheme 35). This is followed by the formation of intermediate 101 by electrolysis-induced SET oxidation. In a parallel electrochemical cycle, benzylic radical species 95 was delivered by the anodic

• 2007, Feroci disclosed an electrochemical strategy for the cis-stereoselective synthesis of chiral β-lactams 180 via a 4-exo-tet cyclization of bromo amides 178 with an acidic methylene group and bearing a chiral auxiliary [101]. The cyclization occurred via deprotonation of the acidic methylene group

• the Re-face in both cases (Scheme 58). Magdesieva and his group developed an electrochemical method for the deprotonation of a Ni(II) glycinate complex containing (S)-o-[N-(N-benzylprolyl)amino]benzophenone [(S)-BPB] 188 as an chiral auxiliary moiety and explored its applicability in

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• furnish the vinylphosphonium ion 6. These two steps have been proposed earlier for the formation of related betaines from acetylenic ketones and esters (see Introduction). A replacement of the N-phenyltriflamide group by the conjugate base of the active methylene compound followed by deprotonation of the