A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• diastereoisomeric secondary alcohols (Scheme 2). The reaction of (S)-citronellal in the presence of 10 mol % of 16 at 60 °C was monitored by 1H NMR observing the rapid disappearance of the triplet signal at 9.78 ppm relative to the aldehyde hydrogen atom and consequent increase of the signals at 4.9 ppm relative to

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylate using gem-dibromomethylarene, oxalacetic acid, and urea [25]. Here the gem-dibromomethylarene moiety serves as an aldehyde equivalent. In addition, utilizing aromatic ketones as a β-ketoester equivalent, the synthesis of 5-unsubstituted DHPM

• -unsaturated ketoesters, such as (E)-ethyl 4-(4-nitrophenyl)-2-oxobut-3-enoate (17), afforded the corresponding 5-unsubstituted DHPM derivative 18 in good yield (entry 6, Table 1). Similarly, heteroaromatic aldehyde derived ketoester 21, also underwent the tandem reaction to give the corresponding 5

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C–H bond, insertion of the olefin into the iridium

• bonds [6][7][8][9][10][11][12][13]. Hydroacylation reactions, the formal addition of an aldehyde C–H bond across a C–C π-system, has emerged as a powerful, and highly atom-economic approach to synthesize ketones. As such, C–H functionalizations are inherently both environmentally benign and economically

• hydroacylation reactions [74][75][76][77][78], we propose a catalytic cycle utilizing iridium that proceeds with three key steps: (1) iridium(I) oxidative addition into the aldehyde C–H bond, (2) insertion of the olefin into the iridium hydride, and (3) C–C bond-forming reductive elimination. The hydroacylation

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• following treatment of acid 5 with hydrazine hydrate, followed by hydrazone formation with the corresponding aldehyde. When subjected to the reaction conditions, oxadiazoles 2k and 2l were obtained in low yield over this multi-step sequence. While unsuitable for large scale reactions, this methodology may

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

• ozonide formed during the reaction [57]. Consequently, no PPh3 or Me2S was required to obtain the crude aldehyde. Subsequent addition of a Wittig ylide gave access to a cyclopeptide with an α,β-unsaturated ester side chain as a (E/Z) mixture. Unfortunately, this compound contained triphenylphosphine oxide

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• in the literature, which generally involve four components. These include one primary amine, two multiple bonds, and one aldehyde function [27]. However, one advantage of our study is that we only used three components since the cinnamaldehyde derivatives 3 played the role of two components at the

• same time, namely that of an aldehyde and that of one multiple bond. Generally, aldehydes and multiple bonds are very reactive in the presence of primary amines. However, since we used cinnamaldehyde derivatives 3, which are conjugated systems of a double bond and an aldehyde, the reactivity was rather

• to the more stable aldehyde form C. In the second step, the nitrogen atom of the enamine function attacks the aldehyde carbon atom of the cinnamaldehyde unit in 3, and one water molecule is eliminated to give the desired product. Both steps are accelerated by the presence of the catalyst. In support

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• ] developed the synthesis of naphtho[1,2-d]oxazole heterocycles from β-NQS as potential antiviral agents capable of inhibiting the HCV virus. Compound 45 was obtained from β-NQSNa (18) as shown above and reacted with substituted benzaldehyde or furfuryl aldehyde to form naphthoxazoles 51a–i and 53a–c

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• afforded the products in excellent yields. The authors also conducted various experimental and theoretical studies to analyze the reaction mechanism. The proposed mechanism begins with the oxidative dehydrogenation of the alcohol to afford the aldehyde which undergoes condensation with ammonia to give the

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• strategy for aldehyde C–H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the

• -electron oxidation of DABCO into its radical cation, the active species responsible for HAT activation of the aldehyde. Our results showed that intermediate amounts of DABCO (0.5 equiv) led to the best results (Table 1, entries 2 and 5; see Supporting Information File 1, Table S1 for details). Unexpectedly

• was the study of the aldehyde scope, using 4-bromophenyl methyl sulfone as a coupling partner. We were delighted to see that both aliphatic and aromatic aldehydes could be arylated using this protocol with good to excellent yields (13–16, 69–89%), although 4-anisaldehyde led to a diminished yield when

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• unstable under basic conditions, readily forming aldehyde products 3. However, related hemi-aminal compounds are quite stable under non-basic conditions, and the motif is even contained in some natural products, such as zampanolide [21] and spergualin [22]. We propose a competing electrocyclization pathway

• 1 in acetone. Preparation and hydrolysis kinetics (inset) of N-formyl product 11. Dashed line: first-order decay fit used in calculating the rate constant. Proposed mechanism for the formation of aldehyde 3 and N-formyl product 8. Supporting Information Supporting Information File 280: Experimental

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• conditions, both primary and secondary alcohols are oxidized to the corresponding aldehyde/ketone, so the chronology of the addition remains unclear whether the reaction proceeds exclusively via an alkyl radical followed by subsequent oxidation, an acyl radical, or a combination of both. Further, slight

• results, the authors proposed a catalytic cycle (Scheme 12). First, the hydroperoxide, in the presence of an Fe(II) species, generates an Fe(III) intermediate and the alkoxy radical which can oxidize the incoming alcohol 67 to an aldehyde 70. Another equivalent of hydroxy radical, either generated under

• a four-component radical dual difunctionalization and ordered assembly of two chemically distinct alkenes 114/115, aldehyde 65, and tert-butyl peroxide (Scheme 23) [108]. In order to selectively couple one alkene to another, without the formation of oligomers, the authors utilized the different

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• base; Introduction Schiff bases are an important class of organic compounds first reported by the German chemist Hugo Schiff in 1864 and are formed from the reversible condensation between a primary amine and an aldehyde or a ketone [1]. Also known as azomethines, aldimines, and more commonly as

• yield obtained for the synthesis of 3bc (R1 = 5-OMe, 75%), the aromatic aldehyde 2c substituted with a similar electron-rich group (R1 = 5-NEt2) gave only a regular 40% yield for 3bb. The structures of the new Schiff bases 3 were characterized by 1H, 13C, and 19F NMR spectroscopy and HRMS techniques

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• (p-TSA) catalyst at reflux (Scheme 1). Sadayoshi and co-workers [39] developed the synthesis of 1,3-oxathiolane derivative 8 (Scheme 2). The protected glycolic aldehyde 3b was isolated after ozonolysis of alkene 3ra. The reaction between an aldehyde 3b and 2-mercaptoacetic acid (3o) was carried out

• -butyldiphenylsilyl chloride (TBDPSCl) for selective protection. The compound was further debenzoylated by ammonolysis, which gave compound 16. Compound 16 underwent oxidative cleavage using lead tetraacetate, and the intermediate aldehyde was oxidized to the carboxylic acid using sodium chlorite, which afforded acid

• ). Sodium periodate was used for oxidative cleavage of cis-diol 3d. The subsequent aldehyde was then converted to a vicinal diol by reduction with sodium borohydride. Further, it was protected by 2,2-dimethoxypropane to give the 1,3-oxathiolane derivative 21. The benzoylated compound 22 was obtained by

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

•  1, entries 7 and 8). The primary alcohol 2k and aldehyde 2l, both bearing oxygen-containing functional groups instead of nitrogen adjacent to the reactive center, gave 26% and 25% of the target compound 3 under these conditions, respectively (Table 1, entries 11 and 12). The TBHP-mediated

• cyclization of primary alcohols like 2k has been successfully utilized in the synthesis of fluorenones and azafluorenones [37], however, the authors used TBHP in n-decane. We repeated the reaction for primary amine 2a, primary alcohol 2k, as well as aldehyde 2l with TBHP in n-decane and obtained fluorenone (3

• ][38][56] (Table 2, entries 10–13), were employed. The yield of aldehyde 2l as the most prominent side product and possible intermediate involved in the oxidative cyclization was also determined. Unfortunately, the initial conditions could not be improved upon, as all the changes implemented had an

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• ratio of 86:14 and high enantiomeric purity of 95:5 er for the major diastereomer (Table 1, entry 1). Using chloroform/isopropyl alcohol 9:1 as the solvent mixture afforded after 120 hours, aldehyde 10a in 45% yield with 83:17 dr and 97:3 er (Table 1, entry 2). The Michael addition in methanol catalyzed

• the base (dr 93:7) but unfortunately with a comparable enantioselectivity (Table 3, entry 2). When the excess of butanal (6a) was reduced from 3 to 1.5 equivalents, the yield again decreased (Table 3, cf. entries 2 and 7). The Michael addition of aldehyde 6a to nitroalkene 7a with K2CO3 and pyrrole

• °C. The experimental results of the addition reactions of aldehydes 6a–c with nitrostyrenes 7b,c catalyzed with (S,R)-C2 are summarized in Table 4. The aliphatic aldehyde 6a in the Michael addition with 4-methoxy-β-nitrostyrene (7b) catalyzed by catalyst (S,R)-C2 gave the corresponding Michael adduct

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• enantioselectivities of up to 93% (Table 24) [65]. The role of the additive is to assist in the formation of the iminium intermediate from the reaction of pyrrolidine with the aldehyde group. Following a similar approach, Guo et al. accomplished the first organocatalytic asymmetric aza-Michael addition of purine bases

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis

• other hand, is proposed to give rise to isolated products 94 (R = Me, Et), 95, and 96. Interestingly, 94 showed anti-inflammatory activity. α‑Iminol rearrangements Whereas α-ketol rearrangements must be driven thermodynamically by the presence of a destabilizing feature in the reactant (e.g., aldehyde

• -ketol rearrangement is believed to give rise to 92 and 93, while a similar sequence at C1 is proposed to yield 94–96. R = Me or Et. α-Iminol rearrangements catalyzed by VANOL Zr (99). The rearrangement can be conducted with preformed iminol 97 or from a mixture of aldehyde 100 and aniline. α-Iminol

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• to generate the CuII hydroperoxo complex C and the corresponding aldehyde. Complex C can undergo a reductive elimination to recover 64a. The liberated aminobenzamide 64a and the aldehyde undergo a condensation reaction to produce quinazolinone 66′, followed by oxidation with molecular oxygen to

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• ) carried out in refluxing toluene using a Dean–Stark apparatus followed by the reduction with NaBH4 (not shown). When the condensation of acetal 1 and aldehyde 2f and the subsequent reduction were carried out in EtOH at rt, according to our procedure applied for the synthesis of aminoacetals 3a–e, the

• proposed a plausible mechanism for the reaction of 6a with diluted HCl (Scheme 10). The mechanism consists of four major steps: the first step is an acid-catalyzed hydrolysis of the acetal function in 6a to afford aldehyde 15; the second step is the enolization of the aldehyde 15 to form the tautomeric

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• and Gandhi reported an Ag-catalyzed cascade cyclization of 6-hydroxyhex-2-en-4-ynals 42 and primary amines to give the 2-(α-hydroxyacyl)pyrroles 43 in moderate to good yield (Scheme 17) [62]. The proposed mechanism involves the condensation of amine and aldehyde to give the imine 44 and the AgNO3

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• the hydrogen source. Following protection of the alcohol moiety with PMBCl, ether 22 was realized in 93% yield. Afterwards, this species was transformed into the γ-keto α,β-unsaturated aldehyde 23 through an NBS-assisted furan oxidation procedure in moderate yield (65%). The keto functionality was

• liberated using TBAF to give compound 27 in 97% yield over two steps. The alcohol group in 27 was then oxidized to the corresponding aldehyde under Swern conditions and subsequently subjected to a Wittig reaction with a two-carbon phosphonium ylide reagent. The desired α,β-unsaturated ester 28 was then

• Jin’s one step dihydroxylation–oxidation protocol using a NaIO4/(cat.) OsO4 system. Allylation of the resulting aldehyde 74 was best performed under Brown’s protocol at low temperature utilizing a chiral allyl reagent prepared from allylmagnesium bromide and (+)-B-chloro-diisopinocampheylborane. By this

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• was demonstrated to be useful for the synthesis of the natural product trisphaeridine (3) [17]. Exposure of 1-bromo-2,4,5-trimethoxybenzene (19) to Suzuki–Miyaura coupling reaction conditions with boronic acid 20 resulted in the formation of aldehyde 21 (Scheme 5). Treatment of 21 with hydroxylamine

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• potassium sodium tartrate solution (Rochelle salt) to furnish the aldehyde 5. Then, transformation of the 7-formyl into the 7-aminomethyl group proceeded via oxime formation, applying hydroxylamine hydrochloride in methanolic ammonia, followed by reduction with Raney nickel to yield the tritylated precursor

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• ] (Scheme 10c) described by Jacobsen and co-workers in 2010 and 2014, respectively [50]. In the one hand, while the thiourea unit in catalyst 43 abstracts the bromide in 45 and forms an electrophilic benzhydryl cation, the free amine group activates the aldehyde substrate 46. The resulting enamine can then

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• radical and toluene as well as aldehyde; iv) product formation in a nickel catalytic cycle; and v) regeneration of nickel(II) species. Recently, the group of Huo developed a nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic acids under visible light irradiation (Scheme

• catalysis under blue light irradiation (Scheme 45) [128]. Among the tested several commercially available photocatalysts, Ir[dF(CF3)ppy]2(dtbbpy)PF6 was found to provide the desired products in good yields. Aldehyde C–H functionalization Inspired by their earlier contributions on HAT-metallaphotoredox

• -mediated C(sp3)–H functionalizations [53][54], the MacMillan group reported a photoredox nickel-catalyzed aldehyde C–H arylation, vinylation, or alkylation [129]. The ketone-forming reaction was conveniently realized by the reaction of aldehydes 89 with aryl, alkenyl, or alkyl bromides in the presence of