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

• reported by the Stahl group [37]. This protocol relies on the sterically encumbered ABNO (9-azabicyclononane N-oxyl) as a mediator, with TMSCN serving as the cyanide source. The reaction operates at low potentials, resulting in high functional group tolerance, even accommodating secondary alcohols

• late-stage functionalizations. In 2020, Ackermann and coworkers reported the challenging C–H alkoxylation of (hetero)arenes with sterically encumbered secondary alcohols via a nickel electrocatalyzed protocol [49]. A traceless removable quinoline amide in the meta position was employed as a directing

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• applicable to the reaction. When 1,1-diphenylethanol (1i) was subjected to electrochemical carboxylation, electroreductive C(sp3)–O bond cleavage and subsequent carboxylation also took place, similarly to that of secondary alcohols, to give 2,2-diphenylpropanoic acid (2i) in 57% yield. Cyclic alcohols and

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• underwent cyclization and dehydration to produce linked polyheterocyclic indoles 75. The authors managed to prepare five adducts in 15–33% yield. Another mechanistic scenario occurred at higher temperature (Scheme 25, conditions b). The secondary amine of diol 73 substituted both secondary alcohols to

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• β-scission, NHC 72 was found to be most effective. Unstrained secondary alcohols were efficiently activated with the help of NHC 65. Deoxygenation of sterically congested alcohols, which has been a longstanding challenge in organic synthesis, was achieved by using a more electrophilic alcohol

• reduction of xanthates. Under blue-light irradiation, xanthates were reacted with B2cat2 (19) in dimethylacetamide (DMAc), providing the borylated product in decent yield. The methodology was metal-free and did not require conventional heating. Nevertheless, the borylation process was limited to secondary

• alcohols. To address the instability of the catecholate products, they were converted in situ to the Bpin esters by introducing pinacol and Et3N into the reaction mixture. In 2021, Wu and co-workers [52] developed a method in which alkyl radicals were generated via photocatalytic deoxygenation of alcohols

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• ). However, N-methylation of anilines with methanol required 100 °C to yield the selective N-methylated products. The same year, Hultzsch et al. designed PN3-pincer ligand-supported Mn(I) complexes for the alkylation of amines with primary and secondary alcohols [42]. Most interestingly, a low catalyst

• -alkylation of aniline with secondary alcohols required a high temperature (100 °C) compared to substituted benzylic alcohols (60 °C). Interestingly, this protocol was used to synthesize the drug cinacalcet, via alkylating the challenging benzylamine substrate under non-optimized conditions. Later, Madsen’s

• secondary alcohols were studied with diazobenzene compounds under the same reaction conditions. Remarkably, the N-methylation was carried out with methanol and deuterated methanol and afforded N-methylated/deuterated products with good yields. The proposed catalytic cycle showed the formation of the amido

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• secondary alcohols 4c,d (R = Me) [30] could be achieved with imidazole derivatives 2a,b under the conditions established above affording within 24–72 h the allylation products 6c,d and 7d in 60–85% yields (Table 1, entries 10–12). Mechanistically, we believe that the nucleophilic allylic substitutions of

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• -disubstituted olefin and reductive epoxide ring-opening giving triol 18. After oxidation of the primary and the secondary alcohols with Dess–Martin periodinane, the remaining tertiary alcohol was protected as a MOM ether and the silyl ether protecting group was removed. The obtained intermediate 19 was then a

• suitable starting material for the SmI2-promoted pinacol coupling, directed by the free hydroxy group, affording a complete selectivity in the formation of the 7-membered ring B. The synthesis of grayanotoxin III was then achieved by acetylation of the secondary alcohols, oxidative cleavage of the MOM

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

• be selectively oxidized in the presence of secondary alcohols. In the case of co-catalysts Fe(NO3)3 or NOx species (NaNO2, HNO3, t-BuONO), an aminoxyl is oxidized in situ to an oxoammonium cation, which oxidizes alcohols. Fe and NOx-based methods demonstrate lower functional group compatibility and

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• secondary alcohols was prepared and subjected to DIBAL (diisobutylaluminum hydride)-promoted selective debenzylation. Debenzylation proceeded by first removing two dichlorobenzyl groups from the 6A,D positions and then removing one or two benzyl groups from the 3A,D positions. Keywords: aluminum hydrides

• are deprotected more readily than the secondary alcohols of 1. Results and Discussion The starting point of the synthesis is the known partially benzylated derivative 6, which according to the literature can be made either from 2 by selective acetolysis of all the primary benzyl groups and ester

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• Abstract The acceptorless dehydrogenative coupling (ADC) reaction is an efficient method for synthesizing quinoline and its derivatives. In this paper, various substituted quinolines were synthesized from 2-aminobenzyl alcohols and aryl/heteroaryl/alkyl secondary alcohols in one pot via a cyclometalated

• secondary alcohols 2 that allowed for the efficient synthesis of a series of quinolines 3 (up to 95% yield and >99:1 selectivity) (Figure 2). A preliminary evaluation of the compounds’ potential antibacterial activity was also performed. Results and Discussion We started our research with the ADC reaction

• (Table 3). It can be seen that quinoline compounds 3 were obtained with excellent yield and chemoselectivity through the cyclometalated iridium-catalyzed ADC reaction of 2-aminobenzyl alcohol and different substituted aromatic secondary alcohols including electron-donating (Me, OMe) and electron

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• the unique methyl ester in azodyrecin The structural diversity of aliphatic azoxy natural products can be attributed to variations in the alkyl side chains and the amino acid-derived counterparts. The variation in the amino acid-derived units is considerably large, as it includes primary and secondary

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

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

• reactions involving the formation of cationic intermediate species [41] like water elimination from an alcohol to provide the corresponding alkene, the isomerization of β-pinene and α-pinene and the cyclization of (S)-citronellal to secondary alcohols. The key point to interpret the action of the capsule in

• performed extra control experiments for each investigated reaction also only with the more symmetrical and less acidic capsule A to underline the effect of the water content on the catalytic activity. (S)-Citronellal isomerization to cyclic secondary alcohols (S)-Citronellal is an enantiopure monoterpenoid

• 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

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

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• -glycosides to demonstrate the scope of acceptors compatible with our glycosylation conditions (Scheme 1). Most of the primary alcohols (2a, 2d–3f) were glycosylated in high yields (up to 91%). In the case of less reactive secondary alcohols (2b, 2h, 2j, 2k) and phenol (2l) better yields were obtained when

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• are the reduction of prochiral ketones to chiral secondary alcohols, transamination of prochiral ketones to chiral amines, hydrolysis of symmetrical diesters to a chiral monoester, and esterification of prochiral diacids or diols. In desymmetrisation reactions, the enzyme initially produces the two

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• first performed on N9-alkylated bistriazole 2c. The reactions were carried out with primary and secondary alcohols in the presence of NaH in DMF. The developed transformation required only nearly equimolar loading of an alcohol and a base, and products 3a–f were obtained in yields up to 83% (Scheme 3

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• (1). Alternatively, the (±)-euphococcinine precursor 6 was prepared from 4, via deprotonation, silylation, and finally, silyl ether cleavage. Swern oxidation of alcohols 5 and 6 gave aldehydes 7 and 8, treated with allylmagnesium bromide, to generate secondary alcohols 9 and 10. These alcohols were

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• are used as the photoredox catalyst to prepare the corresponding primary and secondary alcohols from terminal and internal olefins. The substrate scope is broad, with excellent regioselectivities and yields up to 96% (Scheme 17). Decarboxylation reactions Carboxylic acid often serves as an inexpensive

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• to optically active secondary alcohols (e.g., 342, Scheme 54) [97]. 2.2 Regioselective borylation of alkynes, alkenes, and allenes Cu-catalyzed borylation of C–C multiple bonds involves the formation of nucleophilic Cu–B species that coordinate with a π-system to initially transfer the boryl group

• intermediate. Very recently the asymmetric Cu-catalyzed conjugate borylation (ACB) and addition (ACA) reactions onto α,β-unsaturated 2-acyl-N-methylimidazoles 440 have been developed using nonracemic Taniaphos (L48) as ligand, followed by an oxidation to the secondary alcohols resulting in high

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• (Scheme 18) [49]. Later, the same group explored another application of TEMPO-modified graphite felt electrodes for enantioselective electrocatalytic oxidation of racemic secondary alcohols 45 and 48 (Scheme 19). (S)-Isomers of alcohol 48 possessing a chiral center at α-position to the hydroxy group were

• catalytic amount of 61 (Scheme 24) [59]. A similar strategy using N-oxalyl radicals as chiral mediators has also been explored for the enantioselective electrocatalytic oxidation of secondary alcohols [60]. Tanaka and co-workers subsequently published another article on the kinetic resolution of sec

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• 5-subsituted products (Scheme 1). Quenching of metalated 9d with aldehydes 11a–d while warming to room temperature led to the formation of the expected racemic secondary alcohols 12a–d in moderate to good yields (50–66%, Scheme 1). Any attempts to improve the yields failed. The use of 2.2

• ]naphthyridine (9d) and subsequent conversion into secondary alcohols by reaction with (hetero)aromatic aldehydes. Outcome of a D2O quenching experiment after metalation of 4-bromobenzo[c][2,7]naphthyridine (9d). Synthesis of 5-substituted 4-bromobenzo[c][2,7]naphthyridines via regioselective metalation of 9d

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• successfully used to induce mechanochemical oxidative processes on several structurally different primary and secondary alcohols. The proposed redox process is safe, inexpensive and performing effectively, especially on the macroscale. Herein, an Ertalyte® jar has been successfully used, for the first time, in

• a mechanochemical process. Keywords: AZADO; Ertalyte®; green chemistry; mechanochemistry; NaOCl·5H2O; selective oxidation; TEMPO; Introduction The conversion of primary and secondary alcohols to the corresponding carbonyl compounds (aldehydes and ketones, respectively) is of such importance in

• . In particular, in this study, we used sodium hypochlorite pentahydrate (NaOCl·5H2O) in the presence of a catalytic amount of a nitrosyl radical (TEMPO or AZADO) to induce mechanochemical oxidation reactions on suitably selected primary and secondary alcohols. Performed in a high-energy ball mill and

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• photocatalyst, Cu(tmp)(BINAP)BF4, was found to be active in a photoredox Appel-type conversion of alcohols to bromides. The catalyst was identified from a screening of 50 complexes and promoted the transformation of primary and secondary alcohols to their corresponding bromides and carboxylic acids to their

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• -naphthylamine derivatives has been disclosed, which represents an efficient approach to synthesize aryl ethers with broad functional group tolerance. It is noteworthy that secondary alcohols, such as hexafluoroisopropanol, isopropanol, isobutanol, and isopentanol, were well tolerated under the current catalytic

• system. Moreover, a series of biologically relevant fluorine-aryl ethers were easily obtained under mild reaction conditions after the removal of the directing group. Keywords: alkoxylation; C–H activation; cobalt catalysis; 1-naphthylamines; secondary alcohols; Introduction Aryl ethers are common

• alcohols was first reported by the Niu and Song group (Figure 1a) [30]. Successively, Ackermann realized the electrochemical cobalt-catalyzed alkoxylation via a similar process (Figure 1b) [32]. However, cobalt-catalyzed directed coupling of arenes with secondary alcohols has not been reported so far

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• synthesis [69][70][71][72][73]. The activation of the 5’-primary alcohol is expected to be even more effective than that of the 3’-secondary alcohols (Figure 2), and the 5’-primary alcohol could then be coupled not only to other nucleosides but also various alcohols via a naturally occurring phosphodiester