Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• , reacting BT-SCF3 with carboxylic acids 1 under similar conditions provides (trifluoromethyl)thioesters 3 via a concerted deoxytrifluoromethylthiolation process from tetrahedral intermediate A affording thiocarbamate by-product B [31]. To test whether thioester species could act as intermediates in the

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• as potential inhibitors of cathepsins. The phosphorus atom by default should mimic the tetrahedral intermediate, but this role may also be played by the hydroxy group present in hydroxyphosphonates, which mimic the carbonyl carbon in the peptide bond by forming a hydrogen bond with the amino group of

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• formation of imine 6. Presumably, the combination of Red-Al® and DIBAL reacts with amide 5 to form a stable tetrahedral intermediate that collapses to 6 upon aqueous workup. This type of direct amide semi-reduction using aluminum hydride reagents is, to the best of our knowledge, previously unknown within

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• -TSN7 and 6-TSN9 (Figure 4) are characterized by one imaginary frequency (134i and 163i cm−1, respectively), which corresponds to the N–C bond formation concomitant with C–Cl bond breaking. Both structures support a concerted SN2-type mechanism in which a tetrahedral intermediate does not exist

• for the reaction between N6-substituted adenine anions 1–5 and FcCOCl. In no case the tetrahedral intermediate, typical of a nucleophilic addition–elimination pathway, was located as a genuine minimum on the potential energy landscape. Instead, the structure with tetrahedral geometry corresponds to

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• +. Subsequent attack of water forms a tetrahedral intermediate which results in a cleavage of the acetylated lysine. Most HDAC inhibitors act as substrate mimics and contain a zinc-binding motif. They competitively interact with the HDACs to form stable intermediates and therewith block the active site. Many

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• the unstable tetrahedral intermediate ion E, the breakdown of which leads to a negatively charged 2-organylthioacetate stabilized by both a carbonyl group and the sulfur atom. Finally, a proton abstraction from the reaction medium produces the target product 3. We showed that oxygen plays an important

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

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• employed to determine microscopic rate constants for elementary steps in several ThDP-dependent enzymes. It is notable that, in addition to BFDC [55], E. coli AHAS I and II [57], glyoxylate carboligase [7], DXP synthase [58] and indolepyruvate decarboxylase [59] all have formation of the first tetrahedral

• intermediate as the rate-determining step. Of course, in the absence of the corresponding calculations it is impossible to definitively state that this is due to stabilization of the TC state, but the question is worth asking. The pyruvate oxidase from Lactobacillus plantarum provides some support in that both

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• ester carbonyl of the isatoic anhydride forming tetrahedral intermediate A. Subsequent collapse of the sp3-hybridized carbon to the ketone B with concomitant expulsion of carbon dioxide and enolization affords the ketone C. The anion of the aniline nitrogen then attacks the ketone carbonyl via

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• collapse of the tetrahedral intermediate generates an acyl–enzyme intermediate and the 2,6-dihydroxypyridine product. The subsequent hydrolysis of the acyl–enzyme intermediate then yields the N-methylaminobutyrate product. Other than the preliminary characterization of site-directed mutants of the protein

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• binds to the carbonyl group of ketone 1 to form the tetrahedral intermediate 3 which is referred to as the Criegee intermediate. The next step involves the concerted migration of the R2 group to the peroxide oxygen atom, resulting in the formation of ester 4 and carboxylic acid 5 (Scheme 2). The ability

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

• addition of 1 to aromatic aldehyde generates the tetrahedral intermediate 2. The latter then undergoes a proton shift to furnish an enaminol derivative 3. The aldehyde carbonyl carbon has now transformed into a nucleophilic entity by virtue of conjugation to the nitrogen and sulfur lone pairs. This acyl

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

• fluoroalkylated aromatics. Keywords: β-carbon elimination; carbon–carbon bond cleavage; decarboxylation; tetrahedral intermediate; trifluoroacetate; fluoral; trifluoromethylation; Introduction Organofluorine compounds attract attention because of their applicability in various fields, such as medicine

• indicated that the CF3Cu reagent is directly formed from tetrahedral intermediate A [44] (Scheme 10). The CF3Cu reagent was applied to aromatic trifluoromethylation with aryl iodides, which have electron-withdrawing or electron-donating functional groups, in good to high yields (Scheme 11). The preparation

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

• -acylpyrroles are more reactive at the carbonyl unit and the tetrahedral intermediate is more stable than the Weinreb amides [208]. Based on their previous work on the Strecker reaction [209][210][211], Shibasaki and co-workers used a gadolinium-based catalyst for the 1,4-cyanation (Scheme 25). Overall, this

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• tetrahedral intermediate thus generated, the polyether bridge functions as a leaving group to form an aldehyde intermediate. This is subsequently reduced a second time to the N-CH3 moiety. In compound 22 one formyl group is still present whereas in 23 this has been lost completely. Both compounds were

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• the tetrahedral intermediate Int1 were unsuccessful. Instead, a reaction sequence diverging from the initially formed product P1a of path A was found. Path C involved transformations via high energy bicyclic transition states and/or intermediates. The final products of these latter two paths have

Presence or absence of a novel charge-transfer complex in the base-catalyzed hydrolysis of N-ethylbenzamide or ethyl benzoate

• Shinichi Yamabe,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 185–196, doi:10.3762/bjoc.9.22

• tetrahedral intermediate by O'Leary and Marlier [17]. Marlier suggested that the attacking nucleophile in aqueous solution is water with OH− assistance in the hydrolysis of methyl formate (HCOOCH3) [18]. This suggestion is in sharp contrast to the traditional Bac2 mechanism [19]. In this mechanism, the

• tetrahedral intermediate is formed by direct nucleophilic collisions between hydroxide ions and ester molecules. Marlier's suggestion was supported by a kinetic study of the saponification of ethyl acetate (CH3COOC2H5) [20]. For the base-catalyzed amide hydrolysis, Brown and co-workers made extensive studies

• of the carbonyl 18O exchange and D2O solvent kinetic isotope effects [21][22][23][24][25]. They suggested intervention of a pair of a zwitterion and OH− as well as that of the anionic tetrahedral intermediate (Scheme 1). Although many theoretical studies of the basic amide hydrolysis have been

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

• Takuya Uno,
• Yusuke Kobayashi and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2012, 8, 1499–1504, doi:10.3762/bjoc.8.169

• the cross-aza-benzoin reaction is shown in Scheme 3. Carbene I is generated by deprotonation of triazolium salt 3e in the presence of K2CO3. The carbene I reacts with aldehyde 1 to afford Breslow intermediate II, which could lead to benzoin (6), or tetrahedral intermediate III when treated with α

Kinetic evaluation of the solvolysis of isobutyl chloro- and chlorothioformate esters

• Malcolm J. D’Souza,
• Matthew J. McAneny,
• Dennis N. Kevill,
• Jin Burm Kyong and
• Song Hee Choi

Beilstein J. Org. Chem. 2011, 7, 543–552, doi:10.3762/bjoc.7.62

• electronegative oxygen atoms and the planarity of the phenoxy group (3'), compound 3 [17][39][40] was found to solvolyze in all of the 49 solvents studied solely by an addition–elimination (AN + DN) pathway (Scheme 1) with formation of the tetrahedral intermediate as the rate-determining step. When both oxygens

• a stepwise mechanism via a zwitterionic tetrahedral intermediate [60][61][62][63][64][65]. Isobutyl chloroformate (1) and isobutyl chlorothioformate (2) have found use as specific precursors in novel synthetic routes for the preparation of peptidyl carbamate and thiocarbamate inhibitors of the

• 15 pure and binary solvents. The points for the 100% EtOH, 90% EtOH, 100% MeOH, 90% MeOH, and 20% T-80% E were not included in the correlation. They are added to show the extent of their deviation. Stepwise addition–elimination mechanism through a tetrahedral intermediate for solvolysis of

Tether- directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

• Peter J. Jervis and
• Liam R. Cox

Beilstein J. Org. Chem. 2007, 3, No. 6, doi:10.1186/1860-5397-3-6

• aldehyde in high yield owing to the propensity for the intermediate aldehyde to be reduced further to the corresponding primary alcohol. Presumably in the case of these t-butyl esters, increased steric compression in the initial tetrahedral intermediate causes this to collapse to the aldehyde, even at low