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

• direct amination of MBH alcohols 4a–d, with a poor leaving group (OH). Under the previous conditions (2 equiv of imidazole, toluene, reflux), the conversion of alcohol 4a [28] into the corresponding imidazole 6a was very slow and the starting materials were almost recovered. However, the continuous

• removal of water formed from the direct amination of alcohol 4a by azeotropic distillation shifted the position of the equilibrium in direction to the formation of the allylated imidazole 6a which was obtained in good 88% yield (Table 1, entry 6). The protocol was also successfully extended to the

• reaction of the primary five-membered alcohol 4b [29] with imidazole (2a) as well as to that of alcohols 4a,b with benzimidazole (2b), leading to the SN2-type products 6b and 7b,c, respectively, in 55–80% yields (Table 1, entries 7–9). In addition, we have shown that the direct amination of the available

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• to the core TEMPO or ferrocene charge-carrying moiety. This both increases the solubility of the species and the oxidation potential in aqueous media. TEMPOL uses an alcohol group to the same effect. Redox couples for RFB catholytes are optimized for increasing the oxidation which decreases their

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• ). Their diluted alcohol solutions luminesce with a quantum yield of 0.09–0.23. Pyrazolo[3,4-b]pyridinones 4a–i, 9a, and 10a are characterized by an abnormally high Stokes shift (107–152 nm, 1.07–1.49 eV, Table 2). Such luminophores, which are colorless in daylight but become colored when irradiated with

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• solved in Olex2 using SHELXT and refined using SHELXL (Table 3) [19]. There is some disorder in one water molecule, which was modelled over two positions and some disorder in at least two of the primary alcohol groups, which was modelled. The latter disorder is not uncommon in α-cyclodextrin structures

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• ] and L2 [3] are based on the o-nitrobenzyl scaffold [23][24] and expose a hydroxy group that serves as glycosyl acceptor in the first AGA cycle (Figure 1B). While L1 displays a flexible aliphatic chain terminating with a primary alcohol, L2 carries a secondary benzylic alcohol. Upon irradiation with UV

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• ) and H-6/C-4 indicates the presence of a carboxyl group at C-4. Finally, the HMBC correlations of H-13/C-7 (δC 43.9), C-11 (δC 154.7), and C-12 (δC 65.0) demonstrate that C-7 is connected with acryl alcohol. Thus, the planar structure of 1 was assigned (Figure 1). However, the ROSEY data cannot provide

• mg) was separated by PTLC (petroleum ether/isopropyl alcohol 10:1) to afford eight fractions (Fr.6.7.9.5.14.1–Fr.6.7.9.5.14.8). Fr.6.7.9.5.14.3 (25.4 mg) was further purified by semi-preparative HPLC on YMC-PACK-ODS-A (aqueous MeCN, 65%) to yield 1 (12.7 mg, tR = 28.1 min, flow rate: 3 mL/min). Fr

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• after recrystallization. Subsequent ozonolysis of the terminal alkene functionality with a follow-up reduction furnished primary alcohol 134 which was transformed into the azide 135. Reduction of the azide 135 was accompanied by debenzylation, was followed by tosylation of the primary amine and exchange

• provided ketone 138 which was reacted with an α-keto ester in an intramolecular 5-endo-trig-cyclization process to afford 139. Treatment of compound 139 with sodium borohydride afforded secondary alcohol 140 which after conversion of the tosyl group into a methyl group gave the final product 141 (Scheme 35

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• ]. Although not yet completely clarified, some previous studies on the detailed mode of closure of the C ring in ergot alkaloids from DMAT have been shown to involve, before decarboxylative cyclization, oxidation on the C4-prenyl chain to give the stable rearranged allyl alcohol and/or the relatively unstable

• interconvertible to each other by hydration or dehydration, i.e., a plausible precursor of the allylic alcohol would be the diene, and vice versa [90]. Since both 8 and 10 are easily obtainable from 2 by Mozoroki–Heck coupling with commercially available 2-methyl-3-buten-2-ol, ester hydrolysis (LiOH in THF/H2O

• ), and, finally for 10, dehydration of the tertiary alcohol (mesylation and elimination) (Scheme 3), we decided to test their roles in the photoredox-catalyzed decarboxylative cyclization. With 8 and 10 in hand with the C4-prenyl side-chain already oxidized/functionalized, we recognized that this

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• carbon atoms C-13 and C-14 of the thiazole moiety, the loss of one degree of unsaturation and a loss of 2 Da in mass, it can be deduced that compound 5 possesses an alcohol function. Compound 6 (0.4 mg) was obtained as a brown oil. It possesses a molecular ion at m/z 291.1165 [M + H]+, which suggests a

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• reactivity of their alcohol functions. This allows regioselective chemical modification at either the primary or secondary rim [13]. As a result, these molecular hosts can be specifically linked either covalently or noncovalently to a wide variety of ligands. CDs are a significant part of almost all areas of

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• activity have revealed the presence of antimicrobial peptides [5], defensive alkaloids [6], and defensive long chain alcohol acetates [7]. Historically, in China, numerous records documented the utilization of animals like arthropods for medicinal purposes. Millipedes hereby represent a traditional Chinese

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• ozonolysis reactions [33]. Herein, we describe the feasibility of the honeycomb reactor for aerobic oxidation. Results and Discussion Reaction screening for aerobic oxidation under batch conditions To select the representative aerobic oxidation, the reaction conditions to oxidize 4-methoxybenzyl alcohol (1a

• using the standard tube reactor and the honeycomb reactor (Scheme 4 and Table 5). With benzyl alcohol and benzyl alcohols bearing various substituents such as OMe, Me, Br, CF3 and COOMe at the 4-position and OMe at the 2- or 3-position, the reaction was uniformly accelerated using the honeycomb reactor

• aerobic oxidation using the honeycomb reactor. Flow setup for substrate scope and additional screening. Reaction screening for aerobic oxidation of 4-methoxybenzyl alcohol (1a). Reaction optimization for aerobic oxidation of 4-methoxybenzyl alcohol (1a). Evaluation of the reaction rate using various flow

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• chemodivergent formation of C-3 ethoxycarbonylmethylated and hydroxyalkylated IPs under visible light using water or alcohol as the source of the oxygenated group under degassed conditions [22]. However, all these photochemical methods require the usage of a substantial amount of base, the preactivation with a

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• yields of the corresponding products 3 and the general course of the reaction. However, the structure of the alcohols 2a–c had an effect on the studied reaction. Reactions with isopropyl alcohol 2b required longer reaction times (UPLC–UV–MS monitoring). This phenomenon could be due to the steric factors

• brought in by a bulky isopropyl substituent in alcohol 2b. In addition, in all studied cases we observed that the reaction of APBTTs 1 with alcohols 2 always afforded labile side-products 5 (Scheme 9). Compounds 5 were formed when the nucleophile 2 attacked on the position C3a of the substrates 1. Such a

• , benzylamine, and arylamines 11, while alkylamines are unsuitable for it. Notable, the use of bulky nucleophiles (tert-butyl alcohol (16a), benzyl alcohol (16b), benzhydrol (16c), 2-aminobenzothiazole (16d), HCl) makes it possible to obtain pyrrolobenzothiazoles 17 from compounds 1, but their formation

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• derivatization is possible through the oxidation of the silyl motif to alcohol or the dehydration of the aldol adduct. Other tandem conjugate addition/enolate-trapping reactions In 2016, Nishiyama and co-workers have studied a three-component coupling reaction of alkynes, enones, and aldehydes via direct

• cyclization (Scheme 51A) [93]. The reaction starts with the coordination of the Rh catalyst to the propargyl alcohol 198. In the presence of a base, the rhodium–alkynyl reagent is generated with the concomitant extrusion of benzophenone. Finally, the alkynylation of the enone is followed by the cyclization

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• allylic alcohol isomerization in 137 resulting in the aldehyde 138. This aldehyde, in close proximity to the tertiary alcohol, leads to the production of the hemiacetal 139 which can finally undergo an oxidation producing the final bicyclo[2.2.2]lactone product 136. In 2011, the Radhakrishnan laboratory

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• benzoate (8) lower overall conversion to benzyl alcohol (9) and lower yield was found with 5bm (65% conv. and 53% yield with 5bm, in comparison to 100% conv. and 80% yield with 5ls; Scheme 3a). We hypothesize that the higher amount of CH2Cl2 as part of the prepared complex, which is not a suitable solvent

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• such latrunculin synthesis and the encountered difficulties thereof. Results and Discussion Our synthesis started from commercially available (+)-β-citronellene (10). The ozonolysis of the trisubstituted double bond followed by a reductive treatment with NaBH4 chemoselectively afforded primary alcohol

• 11 in 78% yield (Scheme 1). Due to easier purification, this alcohol was preferred to the aldehyde in our synthetic route, allowing a key stereoselective Krische allylation [21][22] to be envisaged. Applying reported conditions for this allylation – in presence of allyl acetate (10 equiv), [Ir(COD)Cl

• ]2 (2.5 mol %), (S)-SEGPHOS (5 mol %), 3-nitrobenzoic acid (10 mol %), Cs2CO3 (20 mol %) in THF at 100 °C for 24 hours – we obtained homoallylic alcohol 12 in a good 86% yield, with a diastereomeric ratio (dr) of 93:7 deduced from the NMR analysis of the methyl substituent signals in CD3OD (NMR

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• Cham–Lam reactions [23][24][25][26]. However, it has been described that a Mitsunobu reaction of the seco-acid was particularly prone to an SN1 reaction, once the activated allylic alcohol yields an oxyphosphonium ion intermediate due to the conjugation to electron-rich aromatic ring, requiring some

• carboxylic acid 20, which underwent protection with Troc-Cl and selective reduction in the presence of sodium borohydride to form the alcohol 21. After ester hydrolysis the desired seco-acid 22 was obtained in 82% yield. However, several attempts to achieve the macrolactonization of 22 using PPh3 and DEAD

• coupling reaction. Thus, the olefination reaction of aldehyde 15 with phosphonate 23, followed by the reduction of the obtained ester 24 using DIBAL led to the alcohol 25. The latter was submitted to the reaction with carboxylic acid 26 under Mitsunobu conditions [30], giving the corresponding ester 27 in

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• , cyclosporine A and polyvinyl alcohol, ketoprofen and phospholipids, dihydroartemisinin and lecithin, cefixime and ʟ-arginine, flurbiprofen and naproxen/ketoprofen/ethenzamide [50][51][52][53][54][55][56][57][58][59]. Fourier-transform infrared spectroscopy (FTIR) is a very fast, nondestructive and cheap method

• identification of the variables that have significance for these classifications. FTIR–PCA was successfully applied for the discrimination of raw and thermally processed chicken lipid/β-CD complexes [16]. Moreover, raw and recrystallized β-CD samples (from water and alcohol–water solutions) were successfully

• silymarin) are flavanonol derivatives, having a coniferyl alcohol moiety connected through the hydroxy groups in the 3’ and 4’ positions of the aglycone (Figure 1b). FTIR analysis of these flavonoids revealed stretching and bending vibrations corresponding to OH bonds (phenolic or alcoholic, glycosidic and

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• 66. B‒O/B‒H transborylation with HBpin gave the O-Bpin-protected allylic alcohol 67 and regenerated the borane catalyst (Scheme 15). The only example of a B‒F/B‒H transborylation in catalysis comes from Willcox, Thomas and co-workers in the H-B-9-BBN-catalysed arylation of alkyl fluorides with HBpin

• '-binaphthyl (MTBH2) with LiAlH4 as the catalyst gave good yields of the alcohol (70–80%) after workup, but in low enantioselectivities (1–6% ee). A mechanism was proposed whereby reduction of the ketone 91 by the aluminium hydride 92 was followed by Al‒O/B‒H exchange with HBcat (Scheme 23). Roesky reported

• ) [111]. The reaction was proposed to proceed through the enantioselective reduction of the ketone 95 by gallium hydride 96, followed by Ga‒O/B‒H exchange with HBcat to give an enantioenriched alkoxy catechol borane 98, affording the alcohol after workup (Scheme 24a). The mechanism was later explored in

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• ). It also appeared that the RCM depended on the substrate core structure and the presence of a protected allylic alcohol prevented the cyclization to take place. Taking these observations into account, the tricyclic [5-8-5] ring system 45 was obtained using the HG-II catalyst in refluxing toluene

• could not obtain the desired tricyclic compound possessing the required eight-membered ring, but instead they recovered the starting material 47, together with a dimeric product or an eleven-membered ring resulting from a RCM and a retro-aldol reaction. Assuming that the allylic alcohol may induce a

• steric hindrance, alcohol 47 was converted into triene 48 upon dehydration, and further engaged in the RCM reaction. In this case, the use of HG-II catalyst proved to be the best choice to achieve cyclooctene ring formation giving rise to intermediate 49, providing entries for further functionalization

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• is terminated by deprotonation to yield a terpene hydrocarbon or by nucleophilic attack of water to generate a terpene alcohol. For the precursor of sesquiterpenes FPP six initial cyclisation modes are possible (Scheme 1). After ionisation to A either a 1,10-cyclisation to the (E,E)-germacradienyl

• -workers [19], through a sequence of reduction to the alcohol, acetylation and reduction with lithium in ammonia (Scheme 3A) [20], and its structure was unambiguously assigned by X-ray crystallography of a silver nitrate adduct [21]. From natural sources, the compound was first obtained from Humulus

• catalytic hydrogenation to 27, dehydration to a mixture of alkenes (28) and hydrogenation to selinane (29) it was concluded that 11 was a selinane sesquiterpene alcohol (Scheme 9B) [75]. Four years later, based on NMR data Bhattacharyya and co-workers suggested a cis-ring junction for 11 [76], but a

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• deprotonated with LDA at −78 °C in THF and subsequently methylated to give 34 in 99%, followed by treatment with alkynyl Grignard reagent to give the tertiary alcohol 35 in 71% yield. Final elimination with MsCl and NEt3 yielded the desired enyne 25q (49%). When terpene enynes 25p and 25q were submitted to the