Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• Cyclobisbiphenylenecarbonyl (CBBC) represents a readily available chiral figure-eight macrocycle containing two carbonyl groups. However, the transformation of the carbonyl groups has been unexplored. Herein, we conducted the Wittig reaction of CBBC with methylenetriphenylphosphorane to furnish two chiral macrocycles

• formation between carbonyl and alkene units. Keywords: bathtub; chirality; cyclobisbiphenylenecarbonyl; figure-eight; Wittig reaction; Introduction Figure-eight π-conjugated molecules represent chiral macrocycles with a twisted crossover structure [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15

• (TADF), demonstrating that CBBC represents a promising building block for the design of advanced functional materials [17][21]. However, the transformation of the carbonyl groups in CBBC has been underexplored. Herein, we report the Wittig reaction of CBBC 1. CBBC 1 undergoes structural change from a

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• prepared by a Wittig olefination of commercially available 3-oxetanone (Scheme 46) [97]. As for the furan formation, the methodology employs ambient reaction conditions, super-short reaction times and very low catalyst loadings. During the reaction, the oxetane is activated by BF3, opened by the carbonyl

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• constructing Omura’s C1–C11 fragment Yadav and Yadav, in 2013, reported their work on preparing the C1–C11 fragment 61 of borrelidin. Their approach employed an iterative sequence of oxidation, Wittig olefination, hydrogenation, and asymmetric methylation for carbon homologation, alongside Sharpless

• acid, and protection of the secondary alcohol as a TBDMS ether (Scheme 9). Intermediate 63 was planned to be derived from Evans’ amide 64 by reducing the amide moiety to a primary alcohol, oxidizing it to an aldehyde, performing a Wittig olefination to install an unsaturated ester, reducing the ester

• to a primary alcohol, and then conducting asymmetric epoxidation of the double bond. Evan’s amide 64 would be synthesized from primary alcohol 65 through a sequence of oxidation to aldehyde, Wittig olefination to an unsaturated ester, hydrogenation of the olefin, conversion of the ester to Evans

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• -cinnamic acid esters 383–385 and amides 386 and 387 via zwitterionic allene species 389 (Scheme 83B) [142]. 3.1.2 Ylide reactions: The construction of double bond ylide reactions (e.g. Wittig and Horner–Wadsworth–Emmons reactions) is one of the most reliable and stereoselective methods. Several

• catalytic Wittig reaction using phosphetane oxide 412 as redox cycling catalyst using silanes as the reductant to convert aldehydes and α-bromoesters into the corresponding cinnamate esters 44, 154, and 413. The reaction proceeds via formation of nucleophilic phosphane 414 (Scheme 87A) [147]. Moreover

• , Suryavanshi and co-workers (2020) utilized PhI(OAc)2 to mediate the oxidative olefination of amines and Wittig reagents 415 to give the corresponding cinnamate esters 416–419 via formation of imines 421 (Scheme 87B) [148]. In addition, a gram scale operation has been conducted smoothly. 3.1.3 Carbene

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• involving the Ugi reaction between arylglyoxals 1, benzylamines 2, o-azidobenzoic acid (3), and cyclohexyl isocyanide (4a), followed by a triphenylphosphine-promoted tandem Staudinger/aza-Wittig cyclization (Scheme 1a) [33]. The overall strategy was enabled by the presence of an azide group in the

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• 5). The homologous chrysenecarbaldehyde 13 was obtained starting from aldehyde 4 via the same two-step procedure in a 39% yield from 5. Bromophenanthrene derivative 15 was prepared by Wittig reaction between compounds 5 and 7 followed by Mallory photoreaction in a 60% yield from 5. The target

• compounds, F8PIC and F8FUL, were obtained through the Wittig-reaction and Mallory-photoreaction sequence (Scheme 2). Thus, reactions between phosphonium salt 5 and specific aldehydes, 10 and 13, followed by photolysis in the presence of I2 and O2, respectively, afforded F8PIC (57%) and F8FUL (52%). F87PHEN

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• scaffold of simonsol C, utilizing an alkaline dearomatization as the key reaction, followed by a functional-group-selective Wittig reaction and concurrent oxy-Michael addition [6]. A bromophenol acetal was used in the intramolecular alkylative dearomatization, which was first reported by Magnus et al. [8

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• , form heterolignans, which are synthetic derivatives of naturally occurring lignans [22][23][24][25]. This has gained significant attention in drug discovery [26]. Several synthetic routes, such as tandem Pummerer/Diels–Alder or Wittig/Diels–Alder approaches, have been developed for heterolignan

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• post-modification reactions. Examples of these reactions include the Ugi/Dieckmann reactions, Ugi/Robinson–Gabriel reactions, Ugi/Buchwald–Hartwig reactions, Ugi reaction followed by a catalytic aza-Wittig cyclization, Ugi reaction followed by SNAr strategy, Ugi/Heck reactions, Ugi/Huisgen

• -carboxamide-1,4-benzodiazepin-5-ones when enantiopure (S)-(−)-α-methylbenzylamine and arylglyoxals were used. Thus, a reversal of diastereoselectivity was observed depending on the cyclization methodology employed, the reduction of a nitro group or the Staudinger/aza-Wittig on azide derivatives. This

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• esters and N-acyl groups is limited to acetyl, benzoyl, and alkoxycarbonyl groups [15]. Conversely, NAIs derived from α-oxomalonic acid diester are more versatile. Nagao et al. prepared NAI 2 through the aza-Wittig reaction of diethyl mesoxalate (DEMO, diethyl α-oxomalonate). However, only the N-acetyl

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• ) starting from the oxoester 3, which is conveniently available from propenylpiperidine (2) [27] and methyl acrylate [28]. The Wittig reagent 1-methylheptyltriphenylphosphonium iodide (5) was prepared by methylation of the Wittig salt of heptyl iodide (4). A Wittig reaction with 3 afforded an E/Z mixture of

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• Wittig, Julia, Peterson and Tebbe-type reactions, the group of Lambert et al. implemented an elegant electrophotocatalytic carbonyl-olefin cross-coupling in an undivided cell equipped with a carbon felt anode and a platinum cathode in the presence of their own trisaminocyclopropenium cationic

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• with a reduced reactivity in the synthesis of 3H-benzo[e][1,4]diazepin-5-ones, heterocycles previously synthesized by our research group through Ugi/Staudinger/aza-Wittig and Ugi/reduction/cyclization sequences, using 2-azidobenzoic [20] and 2-nitrobenzoic [21] acids, respectively. The first

• methodology has several drawbacks, as the need to synthesise the 2-azidobenzoic acid from anthranilic acid and sodium azide, the requirement of anhydrous conditions to perform the Staudinger/aza-Wittig sequence or the generation of large quantities of triphenylphosphine oxide which needs to be removed by

• reaction took place with a α,3-like relative configuration on the major diastereomer, similar to that obtained for the Ugi/Staudinger/aza-Wittig sequence and complementary to that observed for the Ugi/reduction/cyclization sequence (see Supporting Information File 1, Figure S2). With the aim of building

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• oxidative cycloisomerization reactions for the synthesis of 2-tetrazolyl-substituted 3-acylpyrroles (Scheme 2C) [42]. The Ding group also reported sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag-catalyzed cyclization reactions for obtaining 12-tetrazolyl-substituted (E)-5H-quinazolino[3,2-a

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• . Fessard, Salomé and co-workers used this approach to synthesise a small collection of 2-oxo-BCHs including 42 and 44 (Scheme 4A) [40]. These could then be used as precursors for ortho-benzene isosteric 1,2-BCHs (Scheme 4B) [40]. Carbonyl reduction of 42a yielded alcohol (±)-45a. From 42b, Wittig

• undergo chemical transformations in their synthesis of ketoprofen bioisostere 189 (Scheme 18B) [72]. 1,3-Cuneane 186 bearing two electron-withdrawing groups was accessible by oxidation of 1,3-cuneane 185a. The 1,3-cuneane scaffold was stable to Wittig olefination and Weinreb ester formation (to 187

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• developed a 2-azidobenzladehyde-based reaction sequence including a one-pot [3 + 2] cycloaddition, N-acylation and Staudinger/aza-Wittig reactions for the construction of pyrroloquinazolines and pyrrolobenzodiazepines [73]. The AcOH-catalyzed reaction of 2-azidobenzaldehydes, α-substituted amino acids and

• maleimides in MeCN at 110 °C for 6 h afforded the corresponding monocycloaddition compounds followed by acylation to yield intermediates 22. The subsequent sequential Staudinger/aza-Wittig reaction of intermediates 22 gave products 23a–g in 48–75% yields with 5:1 to 6:1 dr (Scheme 14). This one-pot reaction

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• through an intramolecular aza-Wittig reaction, yielding cyclopropane-fused 2-quinolones [2]. A nitro group not only activates substrates and stabilizes the α-anion as an electron-withdrawing group but also acts as a nucleophile, electrophile, and leaving group, exhibiting diverse reactivities [3]. For

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• have developed a new convenient protocol for the synthesis of 3-sulfonyl-substituted quinolines (sulfonamides and sulfones). The approach is based on a Knoevenagel condensation/aza-Wittig reaction cascade involving o-azidobenzaldehydes and ketosulfonamides or ketosulfones as key building blocks. The

• protocol is appropriate for both ketosulfonyl reagents and α-sulfonyl-substituted alkyl acetates providing the target quinoline derivatives in good to excellent yields. Keywords: aza-Wittig reaction; azides; cyclocondensation; quinolones; sulfonamides; Introduction The quinoline scaffold has a wide

• , the method for the synthesis of 3-acyl-substituted quinolines from o-azidobenzaldehydes and 1,3-dicarbonyl compounds was reported [70][71] (Figure 2a). A combination of Knoevenagel condensation and aza-Wittig reaction allowed to build up target products in high yields. In case of [70], the procedure

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• -pyridobenzazepines 60b via cyclisation of 2,2'-dihalostilbene analogue 58 through a Pd-catalysed double Buchwald–Hartwig amination. The stilbene analogues 58 were prepared by a Wittig reaction with reported yields of the desired Z-isomer around 55%. The amination step was performed on a series of primary alkylamines

• the synthesis of intermediate stilbenes 61 by Wittig coupling. The authors elected to use a Pd2dba3/DPEphos (L4)/Cs2CO3 system (dba = dibenzylideneacetone; DPEphos = bis[(2-diphenylphosphino)phenyl] ether) in toluene after catalyst and ligand screening. Cyclisation of several substituted 2,2

• ]oxepine derivatives 101 (Scheme 21). Lin et al. [62] used copper-catalysed coupling in their total synthesis of bulbophylol-B (105), a substituted dihydrobenzo[b,f]oxepine. The authors synthesised an intermediate stilbene via Wittig reaction, followed by hydrogenation to give dihydrostilbene 104, which

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

• only be favorable after the macrolactonization step. The authors used a convergent route for the formal synthesis of 2. Reaction of 4-bromobenzaldehyde (52) with a commercially available stabilized Wittig reagent led to the formation of the corresponding ester 53. Further reduction of the carbonyl

• convergent route by which it was possible to reach both, compound 2 and 1. Initially, the authors prepared the protected alcohol 66 from aldehyde 52 in a linear sequence (Scheme 12). In parallel, the monobenzylation of 3,4-dihydroxybenzaldehyde (67), followed by chain elongation using the Wittig reaction

• Wittig reaction led to the α,β-unsaturated ester 87, which was subjected to a hydrogenation reaction in the presence of metallic magnesium, leading to the formation of alkyne 88. The cis-alkene was selectively obtained using the Lindlar catalyst. Finally, hydrolysis of the ester led to the formation of

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• in a Michael addition with methyl acrylate, affording aldehyde 4 (Scheme 1). Instead of the original Wittig reaction [13], a Horner–Wadsworth–Emmons reaction using diethyl (2-methylallyl)phosphonate and BuLi led to a higher yield and formation of the pure (E)-isomer 5. The required phosphonate was

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• ]) are linear syntheses involving a great number of steps and purifications as well as cryogenic temperatures. Moreover, the introduction of the C=C unsaturation is achieved via a Wittig reaction or a Pd-catalyzed Sonogashira cross-coupling followed by a reduction by a borane reagent, methods which lead

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

• , protection of the secondary alcohol as a benzyl ether, oxidation of the sulfur and Pummerer rearrangement (Scheme 3). A Wittig reaction gave compounds 8, as a 10:1 separable diastereomeric mixture. A diastereoselective Diels–Alder cycloaddition followed by oxidation of the resulting epimeric mixture gave

• hydrolysis, esterification, and Jones oxidation, affording intermediate 14 with a good 79% yield over 4 steps. Next, the methyl ketone was converted to an enol triflate, and then coupled with Li2CuCN(CH2SPh)2. A reduction of the ester with DIBAL, followed by Dess–Martin oxidation and Wittig reaction lead to

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• unavailable building blocks 7 and 10 were chemically constructed from readily available starting materials. The synthesis of building block 10 commenced with the synthesis of compound 15 through Wittig reaction of Garner’s aldehyde (13) [16], which was readily obtained from tert-butyloxycarbonyl (Boc

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• -substitution. Subsequent transesterification gave the α-ketoester 75, which was used in a Wittig reaction. The undesired Z-configured double bond was isomerized to the E-alkene and final hydrogenation delivered corynoxine (76). (+)-Gracilamine The Mannich reaction was also used by Nagasawa et al. as a key step