A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• single electron transfer (SET), is proposed to be involved in the plausible reaction mechanism. Keywords: arylsulfonylimine; benzylic oxidation; benzyl sulfonamide; K2S2O8; sulfate radical anion; Introduction Among various imine compounds [1], N-arylsulfonylimines are perhaps the most prominent due to

• confirms that the reaction proceeds via a radical pathway. Based on the literature [15][16], our previous experience [14][17][18], and current understanding, a plausible mechanism for the benzylic oxidation is depicted in Scheme 5. Initially, a sulfate radical anion (SO4·−) is generated by homolytic

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• of ethylbenzene and CH-fluorination of aldehydes catalyzed by N-hydroxybenzimidazoles, precursors of corresponding N-oxyl radicals. Mixed hetero-/homogeneous TiO2/N-hydroxyimide photocatalysis in the selective benzylic oxidation. Electrochemical benzylic iodination and benzylation of pyridine by

• . Electrochemical benzylic oxidation mediated by triarylimidazoles. Thiyl radical-catalyzed CH-arylation of allylic substrates by aryl cyanides. Synthesis of redox-active alkyl tetrafluoropyridinyl sulfides by unactivated C–H bond cleavage by tetrafluoropyridinyl thiyl radicals (SPyf). Main intermediates in quinone

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

• aldehyde (33%) being generated (Table 2, entry 11). Similar results were obtained when adding iodine to promote benzylic oxidation [56] (Table 2, entry 12). Finally, Pd(OAc)2 was added in hopes of improving the mediation of C–C bond formation [38] (Table 2, entry 13). Interestingly, here the yield of

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• Information File 1, Figure S7) and δ 6.57 and 7.63 ppm with a J value of 15 Hz for compound 18 (Supporting Information File 1, Figure S9) as inferred by 1H NMR analysis. The resulting Suzuki-coupled products 16 and 18, were subjected to benzylic oxidation expecting the olefin functionality would facilitate

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• was isomerized in the presence of base and dehydrated to give diene 45. Reduction of 45 with 10% Pd/C afforded 8 in good yield (60%) after recrystallization. Benzylic oxidation of 8 (CrO3/HOAc, 45%), followed by C-14 ether cleavage (BBr3) and subsequent sodium borohydride reduction afforded 46 with

• isomerization of olefin 43, the benzylic oxidation of 8, the use of m-CPBA to introduce the C-9,11 epoxide and the non-stereoselective reduction of the C-14 carbonyl group using sodium borohydride, caused an unacceptable overall yield (1.6%). This pioneering work undoubtedly established the basis for the future

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• selectively acetoxylate the tertiary position of adamantane, we sought to apply this approach to the selective acetoxylation of benzylic C–H bonds. As shown in Figure 1, the use of ammonium iodate in combination with an NHPI-type catalyst yielded efficient benzylic oxidation of n-butylbenzene (1a) to 1

• are trapped by molecular iodine which is produced under catalytic conditions via the reduction of iodate. While iodine is produced under experimental conditions via the reduction of iodate, it is not entirely clear what the origin of all the electrons for this process is given that the benzylic

• oxidation is only a net 2 electron process. Previous research shows that the rate of radical trapping by molecular iodine nears diffusion control, similar to that of diatomic oxygen [68][69][70]. This process of radical trapping was probed through the pyrolysis of tert-butyl 2-(naphthalen-1-yl

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• catalyze allylic and benzylic oxidation reactions through a radical mechanism [70]. To implement this tandem sequence in the synthesis of pyran-2-one-annellated coumarins 15 an isomerization of the 8-allyl substituent to a prop-1-enyl substituent was first required. When 8-allyl-7-hydroxycoumarin (8a) was

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• ][8]. Benzylic oxidation is of particular interest because it is a convenient direct approach to arylcarbonyl compounds; it has a long history of research and development, and thus is included among the well-investigated C(sp3)–H transformations [9][10][11][12]. To widen the scope, recent studies and

• acids, such as propionic acid, cyclohexyl carboxylic acid, pivalic acid, and benzoic acid, were also possible by simply replacing PIDA with iodosobenzene (Scheme 3). Here, the addition of 3 Å molecular sieves was essential for removing water derived from the iodosobenzene and to suppress the benzylic

• oxidation forming aryl ketones [52]. Note that the successful coupling of a range of secondary and tertiary carboxylic acids now supports the direct and selective C–H bond activation at the benzyl position by avoiding the formation of carbonyloxy radicals, which are susceptible to decarboxylation. In

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• 5a with PPE/CHCl3 under microwave irradiation led to 1,4-dihydroquinazoline 2a, accompanied by a low percentage of a collateral product. This compound was identified as 2-methyl-1-propylquinazolin-4(1H)-one (6a) (Scheme 3, (a), R1 = Pr, R2 = Me), arising from spontaneous benzylic oxidation of 2a. An

• benzylic oxidation. In spite of this, partial oxidation during workup and purification could not be avoided accounting for the lower yields obtained for the 2-aryl derivatives 2i,j (Table 4, entries 9 and 10). The higher sensitivity of compounds 2i,j towards oxidation may be a consequence of the enhanced

• . Benzylic oxidation of 1,4-dihydroquinazolines (a) and 3,4-dihydroquinazolines (b). Selective N-acylation of 2-ABA and its derivatives. Synthesis of compounds 5. Synthesis of 3,4-dihydroquinazolines 1. Synthesis of 1,4-dihydroquinazolines 2. Supporting Information Supporting Information File 94

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• , obtained via Au-catalyzed Meyer–Schuster rearrangement. Assembly of 5-oxygenated bisindolylpentenones. DMB: 3,4-dimethoxybenzyl, DMFDMA: N,N-dimethylformaldehyde dimethyl acetal. Benzylic oxidation as side reaction of DMB removal. Hydroxyalkylation of N-protected indoles with β-cyclocitral and SnCl4

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• CORMs in place of the commonly used gaseous CO was found to be an attractive alternative for assessing P450 concentrations in whole cells. In a comprehensive pooling approach, P450cam mutants were shown to exhibit improved activities in the benzylic oxidation of ethylbenzene derivatives. The

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• 4d during N-arylation (monitored by GC–MS). Formation of byproduct 13 via benzylic oxidation. Routes towards 1,2-diarylindoles starting from indole; a: PhB(OH)2 (3 equiv), Pd(OAc)2 (5 mol %), AcOH, O2, rt, 12 h; b: CuI (10 mol %), DMEDA (20 mol %), K3PO4 (4 equiv), toluene, 135 °C, 12 h. Palladium

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• annulated cycles and their possible modification, whereupon the main focus was the preparation of several D-ring derivatives. The anthraquinone moiety 11 should be formed within the last steps of the synthetic approach by benzylic oxidation of compound 12 (Scheme 3). The terminal silyl group and the silyl

• 27a the FeCl3-catalyzed benzylic oxidation proceeded smoothly with yields of up to 70% [50]. A final hydrolysis with hydrochloric acid afforded the desired carbohydrate-based anthracycline derivatives 11 in good yield (Scheme 6). Conclusion In conclusion, we have developed a concise and robust

• carbopalladation sequence generating both, the B and the C-ring of the system in a single step. Further derivatisation included the cleavage of the silyl ether and two-fold benzylic oxidation to the quinone moiety. We believe that these natural product mimics might be of interest as useful candidates for drug

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• synthesis of smyrindiol was described by the group of Grande [8]. Starting with the naturally occurring dihydrofurocoumarin (−)-prantschimgin (2), the hydroxy group in 3-position was introduced by a Cr(VI)-mediated benzylic oxidation, followed by a diastereoselective sodium borohydride reduction (Scheme 1