Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• a single diastereomer (Table 1, entry 4). To explain this diastereoselectivity, we hypothesize that the C–O bond, which occupies an axial position in the proposed transition state TS-1, could avert an additional hyperconjugative interaction (σ*C-O/π) that renders the reacting C=C bond electron

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• underwent a reductive interrupted Fisher indolization with phenylhydrazine to give indoline 281. To forge the C16 stereocenter and form the C–O bond at C2, diol 282 was prepared from 281 in six steps. Treatment of 282 with MeI/Cs2CO3 induced cyclization through putative indoleninium intermediate 283

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• -substrates with the potential to react with metal carbenoids in many different ways [14], for example through O–H, N–H or formal C–H insertion, cyclopropanation, or oxazole [20] formation. The 16 co-substrates, selected from available compounds in our laboratory, are shown in Figure 2 (panel A). Many of

• these substrates had more than one potentially reactive site to enable, for example, O–H insertion (C1–5, C8, C11 and C14), N–H insertion (C3, C6, C12, C13 and C15), formal C–H insertion (C1, C3, C4, C12, C15 and C16), oxazole formation (C9 and C10) and cyclopropanation (C7, C10, C14 and C16). To start

• reactions, a product with molecular weight consistent with O–H insertion into water was also observed. For these 18 substrate/co-substrate combinations, the reaction with the highest estimated yield was selected for mass-directed purification (Table 2). In total, 23 intermolecular reaction products were

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• chemical literature regarding the biological activity (including anticancer properties) of phosphoric esters, reports on biological studies of systems based on the P=O fragment and oxirane skeletons are less common. Nevertheless, systems containing both of the mentioned structural motifs are rarely

• of chlorophosphine oxides (methylphosphonic dichloride MeP(O)Cl2; methyl dichlorophosphate (MeO)P(O)Cl2) and phosphorus oxychloride P(O)Cl3 with racemic glycidol in CH2Cl2 in the presence of KOH as basic agent (Scheme 1). Further filtration and final distillation at low pressure leads to the products

• voltammetric wave, the aqueous solution was actively stirred with a magnetic stirrer in an atmosphere of constant inert gas flow. Starting materials. Methylphosphonic dichloride MeP(O)Cl2 and methyl dichlorophosphate (MeO)P(O)Cl2) [30] were prepared according to literature procedures. Phosphorus oxychloride P

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• catalytic sites. The OH group on the phosphorus atom functions as a Brønsted acid site, while P=O serves as a Lewis base site, which enables the simultaneous activation of both nucleophiles and electrophiles in one reaction (Figure 1). The chiral properties of the catalysts are derived from the chiral

• macrocyclization strategy [53]. Starting from the linear precursor 60 bearing two triazine moieties, the intramolecular SNAr reaction catalyzed by CPA 13 (30 mol %) led to macrocyclization, which produced the inherently chiral N3,O-calix[2]arene[2]triazines 61 with high enantioselectivity, albeit in moderate yield

• ]arenes displayed a distinctive 1,3-alternate conformation, notably differing from the typical cone conformation of the conventional calix[4]arenes. Moreover, unlike previously documented examples, the inherent chirality of these products arises from the difference of just one heteroatom (O and NH) in the

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• symmetrical diazocines is more demanding compared to classical azobenzenes since the two aromatic rings are not only connected via an azo-bond, but also have to be linked by an alkyl chain first. For that, more synthetic effort is required. It can be performed through oxidative dimerisation of o-nitrotoluene

• (37) followed by reduction with Zn/Ba(OH)2 and partial re-oxidation (Scheme 12A) [52]. They can also be obtained from o-halogenated benzyl bromides 40 by lithium–halogen exchange followed by nucleophilic substitution and a second lithium–halogen exchange with iodine (Scheme 12B) or by nickel-catalysed

• reaction can also be used to prepare precursors for the Ullman–Goldberg coupling (Scheme 12B and 12C); however, in the presence of halogens, an alternative reduction pathway of the alkene with tosylhydrazine and NaOAc must be used [55]. Hetereodiazocines 35b and 35c are synthesised by coupling of o

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• transformations. For example, compound 7e underwent both sulfone formation and S/O atoms exchange in the heterocyclic core. For derivatives 6 and 8, any oxidation conditions resulted in even more complex product mixtures (presumably due to the additional sulfur atom in the second ring), whose structures could not

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• through a σ-type intermolecular halogen bonding (C–Br···O) between the ortho-bromine atom and the carbonyl oxygen. The formation of similar heterochiral polymers through a σ-type intermolecular halogen bond (C–Br···S) was also found in crystals of the thio-analogue rac-II. On the other hand, in the

• intermolecular interaction (halogen bonding) between chiral compounds possessing an amide group and a thioamide group are quite rare [21]. We were curious as to whether the chirality (racemate/optically pure form)- and the functional group (C=O/C=S)-dependent halogen bonds found in I and II are also observed in

• mebroqualone rac-I was very similar to that of the thione analogue rac-II [the formation of heterochiral polymers through a σ-type halogen bond (C–Br···O or C–Br···S)]. In contrast, the intermolecular associations in the crystals of racemic quinoline-2-thione rac-2a significantly differed from those of the

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• methoxymethyl group cleavage, O-to-N rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyloxazoline. The reactivity of the electron-deficient double bond in the vinyloxazoline was explored in several

• ][24] (Scheme 1). The proposed strategy relied on the N-deprotection of the intermediate ester 3d inducing O-to-N rearrangement to form amide 5 as a precursor of vinyloxazoline 6. For this purpose, Alloc (allyloxycarbonyl) turned out to be a suitable N-protecting group as it was compatible with the

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ]. However, under the same coupling conditions (Pd2(dba)3, P(o-Tol)3, n-Bu4N+OH−, toluene/H2O, 90 °C), the reaction of diiodide 1 with bisboronic acids 75/6/7/8 gave only low yields of the desired macrocycles Me-M1 (7/32/22/21% for Me-M15/6/7/8). Thus, the macrocyclization via two-fold Suzuki coupling was

• routes towards macrocycles featuring one BINOL unit. a) Two-fold Suzuki coupling and b) two-fold Williamson synthesis. Reagents and conditions: i) bis(boronic ester) 75/6/7/8 (1.0. equiv), Pd2(dba)3 (0.1 equiv), P(o-Tol)3 (0.2 equiv), n-Bu4N+OH− (3.2. equiv), toluene/H2O 5:1, 90 °C; ii) ethylene glycol

• shown. Initially attempted route towards bis-BINOL macrocycles based on precursors Me-36 or Me-46. Conditions: i) 96 (2.2 equiv), Pd2(dba)3 (0.1 equiv), P(o-Tol)3 (0.2 equiv), n-Bu4N+OH− (3.2 equiv), toluene/H2O 5:1, 90 °C; ii) 96 (2.2. equiv), Cs2CO3 (3.0 equiv), CH3CN, 80 °C. Synthetic route towards

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• typically exist as a mixture of anomers which complicates their use in the chemical glycosylation reactions. Earlier approaches to constructing 1,1'-O-glycosidic bonds often relied on the use of simply and symmetrically protected (benzylated or acetylated) monosaccharide building blocks, enabling the

• tetrabenzylated glucose lactol acceptor 2, resulting in the formation of the β,α-1,1-linked diglucoside 3 (Scheme 1) [49]. The application of a the 2,3,4,6-tetra-O-benzyl trichloroacetimidate donor 4 resulted in the same disaccharide product 3, albeit as part of a mixture with other diastereomers [51]. The

• formation of an α-glycoside on the donor side [54]. On the acceptor side, the β-configuration was favored due to steric hindrance from the C-2 phthalimido group in the triacetylated GalN-lactol acceptors 6 or 3,4-di-O-benzylated acceptors 8, resulting in kinetically controlled formation of β,α-1,1

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• classifications necessitate tailored nitrating reagent selections, giving rise to fundamentally distinct mechanistic pathways. This reactivity is exemplified by the comparative kinetic profiles: N-nitration of amines and O-nitration of alcohols – facilitated by accessible lone electron pairs – exhibit markedly

• , achieving 54.98% o- and 45.01% p-nitrophenol yields within 15 minutes [10]. Umrigar et al. demonstrated a microwave-assisted nitration of monochlorobenzene (MCB) for the efficient synthesis of 2,4-dinitrochlorobenzene (2,4-DNCB), achieving reduced reaction time, minimized waste acid, and enhanced yield

• nitric acid and the model was formulated to predict the reaction outcome at large capacity. Lan and Lu [32] developed a method for the rapid determination of lumped kinetics for the nitration of o-dichlorobenzene by processing the profile of adiabatic temperature rise in a micropacked-bed reactor. Type B

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• modifications of bacterial polysaccharides, and the interaction of 4,6-O-pyruvylated pyranoses with lectins depends on the stereochemistry of the pyruvate ketal. Moreover, this chemical modification is crucial, as the distinct R or S diastereochemistry at the ketal center directly influences its biological

• confirming their structure by using X-ray crystallography as direct evidence. Subsequently, the pyruvylated galactose was further applied in the synthesis of zwitterionic polysaccharide A1 (PS A1) precursor. Results and Discussion In the initial experiment, p-tolyl 2,3-di-O-acetyl-1-thio-β-galactopyranoside

• a = 16.1017(4) Å, b = 7.7608(2) Å, c = 28.8344(8) Å, and β = 93.3680(10)°. Additionally, the presence of lattice water greatly influenced the molecular packing. The hydrogen bond (H–O–H) lengths in this lattice water ranged from 1.923 to 2.204 Å (Figure 2b). The pyruvylated galactose 6 was utilized

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• reductive elimination to afford INT-IV. Finally, migration of the Piv group from O to N gave the product 17a. Moreover, the Pd-catalyzed isocyanide insertion approach has been successfully extended to the generation of helical chirality [31]. As shown in Scheme 4a, phenyl diisocyanides 21 or 22 underwent

• thionolactones, getting rid of the pre-formation of stoichiometric Ru-complexes [52][53]. Mechanistic investigations indicated that this transformation proceeds through a two-step sequence promoted by the same catalyst: 1) the diastereo- and enantioselective [3 + 2] cycloaddition to generate spiro-S,O-ketal 52

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• rigid, with only small modifications on going from the ground state to the first single excited state (Figure 6). However, the presence of the two perchlorate anions results in additional coordination with Ba2+, thus resulting in larger values of the Ba–N distances, as well as of the average Ba–O and Ba

• [33] calculations were performed using the B3LYP[34][35][36], B3LYP-D3BJ [37][38], CAM-B3LYP [39], M06 [40][41], M06-2X [42], M06-L [43][44][45], PBE0 [46] and ωB97XD [47] functionals. The 6-311+G* and 6-31++G** bases sets [48][49] were used for C, N, O, and H. The DefTZVPP [50] effective-core

• (⟨RBa0⟩)n denote the average Ba–O bond distances (in Å) for the different crown ethers. Distances between Ba2+ and the ring points of electron density of benzene (in green) are also gathered in (B). ΔGiso and ΔGrxn terms stand for the Gibbs energies (in kcal/mol) described in Scheme 2 and have been

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• associated with high barriers (>40 kcal/mol). However, we found that the Meerwein–Ponndorf–Verley-type reaction involving the double hydrogen migration from CH3–OH to O=CH2 proceeds with a much lower activation barrier of ca. 25 kcal/mol [79]. Interestingly, although the analogous reaction involving CH3–CH3

• and O=CH2 proceeds with a much higher barrier, both transformations feature transition states whose in-plane aromaticity is nearly identical according to their NICS(3, +1) values (−24.5 ppm vs −27.2 ppm, respectively). Therefore, it is found once again that there is no clear relationship between the

• TS-aromaticity and the barrier heights. The origin of the computed decrease of the activation barrier in the CH3–OH to O=CH2 as compared to the analogous reaction involving ethane as hydrogen donor can be initially traced to different C–H vs O–H bond strengths. Indeed, we found that the total bond

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• ABz 7, Man PVB 8, and Man 9 through orthogonal one-pot glycosylation strategy (Scheme 1B). The 2-O-Bz group in 5–8 served as the neighboring participating group for the stereoselective construction of 1,2-trans-mannosidic bonds, while the 3-O-Lev group in 6 was the temporary protecting group for (1→3

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• local excited (LE) and charge-transfer (CT) states can be experimentally observed as dual fluorescence: a structured, higher-energy emission from the LE state and a broad, red-shifted emission from the CT state [8][9]. Classical systems such as 4-(N,N-dimethylamino)benzonitrile (DMABN) and pyrene-o

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• , respectively [19][20]. Recently, our group established an efficient synthetic strategy for strained macrocyclic polyarenes, such as compound C, in which o-phenylene units preorganize adjacent heteroaromatics into close proximity, thereby facilitating oxidative ring-closure reactions [21]. Among these, the

• thiophene units [24][25]. The influence of heteroaromatic positioning on the reaction outcome has been rationalized in our previous work [25]. As a further extension of this molecular design, herein we report the synthesis of an o-phenylene-pyrrole-thiophene hybrid icosamer and its oxidative fusion to yield

• an aza[5]helicene-incorporated macrocycle. The resulting cyclophane-like structure and its optical properties have been analyzed in detail. Results and Discussion Synthesis and characterization Synthesis We obtained o-phenylene-pyrrole-thiophene hybrid icosamer 4 during our attempt to synthesize

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• of nitrile oxides to isocyanates or their dimerization [26][27]. Since isomerization is believed to be the primary direction of molecule degradation only for bulky o,o'-disubstituted aromatic dipoles [28][29][30], the main efforts in developing a methodology were focused on suppressing dimerization

• -substituted aromatic group, we have observed atropoisomerism (Figure 2) what is manifested by the appearance of a second set of signals in their NMR spectra. As the previously studied similar structures (Y = N–R) [22], products 5b and 5d (Y = O) were formed through the addition of a dipole molecule, resulting

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• five-membered heterocycles via [3 + 2]-cycloaddition reactions. Depending on the type of the dipolarophile used in these reactions, the target heterocycles may contain only one sulfur atom (cycloadditions with C=C or C≡C dipolarophiles) or more heteroatoms (cycloadditions with C=S, C=O, C=N, N=N, S=O

• , N=S=O, etc. dipolarophiles) [5][6][7][8][9][10] (Scheme 1, upper part). Notably, [3 + 2]-cycloadditions of the sterically crowded thiocarbonyl S-methanide 1b with electron deficient, tetrasubstituted ethylenes activated with CN and CF3 (or CN and CO2Me) groups were encountered as the first examples

• sulfur (χ = 2.55 (for C) and χ = 2.58 (for S) according to the Pauling scale), thiocarbonyl S-methanides 1 are considered as electron-rich 1,3-dipoles with basic and nucleophilic reactivity displayed by the =S+–CH2‒ unit [6]. Therefore, acidic compounds of type R–XH (X = NR’, O, S), which are able to

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• achieved in case of o-halo-substituted diaryliodonium salts providing 64% and 67% for amides 2bg and 2bh, respectively. In contrast, iodonium salts with electron-rich aryls afforded the corresponding benzamides 2aa, 2ba, 2bb, 2bf, and 2bk in significantly lower 19–36% yields. Subsequently, various

• not significantly change for EWG- or EDG-substituted species except for extreme cases [44]. Additionally, such reactivity pattern cannot be explained only by steric factors since the yield dramatically dropped for o-methyl-substituted iodonium salt 1f compared to o-halo-substituted salts 1g and 1h

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• . In their contribution, Son et al. focus on transformations via the formation of copper nitrenoids, particularly amidations via oxidative insertion to N–O bonds and reductive elimination, and a small number of other reactions. The final Review by Cho, Lee, and co-workers is useful for the scientific

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• open derivative, and the subsequent ring oxidation upon closure (as shown in the mechanism in Scheme S1 (Supporting Information File 1), the reaction mixture may contain the desired 2-substituted benzoxazole 2a together with its open-form precursor 2a-o. The latter can be hydrolysed to give N

• -formylpiperidine and aminophenol (2a-o-hydrol) (see Figure 1a). To better understand the influence of the reaction conditions on product distribution, we plotted conversion versus selectivity in Figure 1b. Crudes were analysed by 1H NMR spectroscopy, as shown in Figure S1 (Supporting Information File 1), to

• determine the percentage composition of starting material and products 2a, 2a-o and 2a-o-hydrol. The reaction was perfectly reproducible and no other derivatives were observed. As shown in Figure 1b, when the reaction was conducted without a catalyst, only ring opening was observed, accounting for 47%. By