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

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• dimerized 7,7’-bis(indolyl) products 185 with the 2-methyl group transformed to the aldehyde in the same step (Scheme 27) [118][119]. The less electronically activated N-acyl substrate gave a slightly better yield. Selenation occurs at C-3 instead of C-7 for the C-3 unsubstituted substrates. Conclusion This

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• triarylmethane in 93% yield, indicating that this reaction strongly depended on the nature of the aromatic aldehyde [44]. Synthesis of substituted anthracenes from anthraquinones An easy and common method to obtain anthracenes is to reduce anthraquinones by using several reagents. An important advantage of this

• intramolecular Friedel–Crafts-type cyclization. This was the first report of the same molecule bearing an acid-sensitive acetal and dibenzyl alkoxy groups. The key steps described in the work were protection of the aldehyde group of 6-bromopiperonal (80) by using 1,2-ethanediol or 1,3-propanediol, followed by

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• synthesis of 3,4-dihydrocoumarins 80 bearing a cyclohexene ring, through [4 + 2] cycloaddition between 2,4-dienals 79 and 3-coumarincarboxylates 43. This stereoselective transformation was performed using a squaramide 81 derivative catalyst, which activates the aldehyde with the formation of an enamine

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• inspired by the biocatalytic action of the cytochrome P-450 cycle, which is driven by a reductase or bioreductant, and presented high versatility in incorporating both aldehyde and ketone functionalities into unprotected arylboronic acids. The reaction consists of using a porphyrin-based iron catalyst, and

• same year, Wu, Li and co-workers described a successful cobalt-Cp*-catalyzed C–H amidation of benzaldehyde derivatives (Scheme 39B), in which the aldehyde portion works as the directing group [198]. After an acid workup using diluted hydrochloric acid, the desired ortho-amidated products were obtained

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• research. This has been explored utilizing the reactivity between primary amines and the aldehyde moiety of a 2’-O-(2-oxoethyl)uridine nucleotide, incorporated centrally in an 11-mer TFO, to form a Schiff base (monomers 41–45) [80]. All aminoalkylated moieties improved the triplex stability. Notably, a

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• with the prenylation of ʟ-tryptophan to dimethylallyltryptophan (DMAT). During several steps DMAT is converted to chanoclavine-I aldehyde, the last mutual intermediate. Branching into different pathways after this intermediate is mainly due to differences in the function of EasA, the enzyme catalysing

• the next biosynthetic step. In A. fumigatus EasA acts as a reductase and after additional steps chanoclavine-I aldehyde is converted into festuclavine (16) (Figure 6). Festuclavine is then oxidized to fumigaclavine B (17) which in turn is acetylated to fumigaclavine A (18). Finally a reverse

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• benzylic alcohol selectively to the aldehyde or ketone is still desirable. Recently, cerium photocatalysis was introduced as a robust alternative to generate oxygen or carbon-centered radicals under mild reaction conditions [57][58][59][60][61][62][63][64]. CeCl3 reacts via ligand-to-metal charge transfer

• 1ad and 1ae gave the ketones 2z, 2aa, 2ab, 2ac, 2ad, and 2ae in good yields. However, the primary aliphatic alcohol 3-phenylpropanol (1af) did not provide the desired aldehyde at all, and allylic alcohols such as geraniol (1ag) and cinnamyl alcohol (1ah) afforded the aldehydes 2ag and 2ah in very low

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

•  2). This second route commenced with a three-step protecting group manipulation of primary alcohol 6, delivering 7 in 63% yield over three steps (Scheme 2). Alcohol 7 was then subjected to Parikh–Doering oxidation to deliver a crude aldehyde in 98% yield, from which oxime 8 was subsequently formed

• latter synthetic steps towards 5, an alternative, one-pot three-component procedure (H2N-OH, NaN3 and catalytic [(NH4)4Ce(SO4)4]) was attempted from the crude C6-aldehyde [17]. TLC analysis indicated C6-nitrile formation was evident after 36 h, however, the desired C6-tetrazole 5 was not observed

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -promoted condensation of a homoallylic alcohol and an aldehyde to give an oxocarbenium ion, which is then reacted with an olefinic/alkynic bond generating a carbocation that undergoes a Friedel–Crafts reaction. Given the potential value of tetralin-2-ol scaffolds to drug research programs, we decided to

• develop a novel Prins/Friedel–Crafts cyclization strategy for the synthesis of 4-aryl-2-hydroxytetralins starting from 2-(2-vinylphenyl)acetaldehydes (Scheme 2). In this protocol, we envisioned that the aldehyde 5 would give rise to an oxocarbenium ion species 6 upon treatment with a Lewis acid. The

• hydrolysis using 18% aq HCl furnishing the corresponding aldehyde [21]. Without purification, the resultant aldehyde intermediate was then directly reduced using potassium borohydride to the corresponding primary alcohol 11a in 74% yield starting from 9a. Pd-catalyzed cross-coupling of 11a with pinacol