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

• 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

• ]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

• coupling in dibenzo[b,f]oxepine synthesis. Wittig reaction and Ullmann coupling as key steps in dihydrobenz[b,f]oxepine synthesis. Pd-catalysed dibenzo[b,f]azepine synthesis via norbornene azepine intermediate 109. A simple representation of olefin metathesis resulting in transalkylidenation. Ring-closing

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

• 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

• intramolecular Wittig reaction to promote the macrocyclization in the formal synthesis of compound 2. Initially, the authors synthesized the fragment 14 from the starting aldehyde 80 by using a Wittig reaction followed by hydrogenation using ammonium formate (Scheme 17). Concomitantly, 4-formylphenylboronic acid

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

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• (trimethylsilanyl)diseleno[2,3-b:3′,2′-d]thiophene ((TMS)2-bb-DST), and 2,5-di(trimethylsilanyl)diseleno[2,3-b:3′,2′-d] selenophene ((TMS)2-bb-DSS) were used as starting materials to synthesize three S-shaped double helicenes (i.e., DH-1, DH-2, and DH-3) through monobromination, formylation, the Wittig reaction

• sulfur atoms on the same side is defined as bb by us. The double Wittig reaction of 4a and 4b with 1,3-phenyldimethyltriphenylphosphonium bromide afforded compounds 5a and 5b with yields of 46% and 64%, respectively. After the double Wittig reaction of 4c we obtained a mixture of cis and trans isomers of

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• /addition/nucleophilic substitution reactions. Keywords: aza-Wittig reaction; 3,4-dihydroquinazoline; 4H-3,1-benzothiazine; nucleophilic substitution; Passerini reaction; Staudinger reaction; Introduction The chemistry of 3,4-dihydroquinazolines and 4H-3,1-benzothiazines is of constant interest owing to

• reaction has also been utilized widely in preparation of various heterocycles under mild neutral conditions [30][31][32]. Recently we have reported the synthesis of 3H-2-benzoxepin-1-ones, 4H-3,1-benzoxazines and oxazoles by combination of a Passerini with an intramolecular aza-Wittig reaction [33][34][35

• ]. Continuing our interest in the synthesis of N-heterocycles via the aza-Wittig reaction and multicomponent reactions [36][37][38], we wish to report herein a facile synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• NMR spectra. The solubility issues forced us to investigate also other modification protocols. Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary

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

• 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

• primary alcohol 99 (90%). Oxidation of this moiety with IBX to its corresponding aldehyde served as a substrate for the two-carbon homologation via Wittig reaction giving ester 96 in 80% yield over the two steps. After reduction of the ester group to its primary alcohol counterpart, the Sharpless

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• fourth and final step, phenoxydiphenylalkene derivative 4a was prepared by a Wittig reaction, which was carried out using methyltriphenylphosphonium bromide with ketone 3a, in basic medium, at room temperature, and dry THF. After the structures of the starting compounds were elucidated, the method

• synthesized by Grignard reaction of 1a–l and aryl(or alkyl)magnesium bromides. Then 3a–l were prepared by oxidation of 2a–l using PCC. The final alkene compounds 4a–l were obtained by Wittig reaction using Me(Ph)3PBr, t-BuOK, and NaH. All substrates were purified by crystallization or column chromatography

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

• methodology, they synthesized 2,3,6,7-anthracenetetracarbonitrile (90) in a good yield (84%) by double intermolecular Wittig reaction of the protected benzenetetracarbaldehyde 87 with reagent 88, followed by deprotection and double ring-closing reaction of intermediate 89; they used a mixture of triflic acid

• /water in the first step and trimethylamine in the next reaction step [56]. Other procedures In 2008, Lin et al. reported a homo-elongation protocol to obtain acene diesters and dinitriles starting from dialdehydes (Scheme 23) [57]. This methodology was based on a Wittig reaction between substituted [n

• Wittig reaction affording naphthalenes 144. Isomerization of compounds 144 produced substituted styrenes 145. With the styrenes 145 in hands, the authors employed the Grubbs II catalyst-promoted ring closure to obtain the benzo[a]anthracenes 146a (85% yield) and 146b (43% yield) [67]. Other procedures In

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

• Scheme 3 consisting of the following steps: (i) Wittig reaction of 2-bromobenzaldehyde with methyltriphenylphosphonium iodide ylide, (ii) lithiation of the resultant o-bromostyrene with n-BuLi and reaction of the aryl lithium species with ethylene oxide, and (iii) oxidation of the resultant primary

• -vinylphenyl)acetaldehyde (13a) using the route as outlined in Scheme 4. The synthesis started with the Wittig reaction of 2-bromobenzaldehyde (9a) with (methoxymethyl)triphenylphosphonium chloride (MTPPC) upon action with n-butyllithium in THF at 0 °C to give the vinyl ether 10a that was subjected to acidic

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• Wittig reaction with methylenetriphenylphosphorane (Ph3P=CH2) produced the 5′-methylene derivative [62]. Finally, oxidation with meta-chloroperbenzoic acid (mCPBA) afforded the nucleoside 97. Treatment of the nucleoside 97 with Grignard reagent PhMgBr in THF produced nucleoside 98, whose secondary

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• . Consequently, we decided to develop a new synthetic strategy for the preparation of trigonoine B (1). Carbodiimides are valuable synthetic intermediates that can be obtained by an aza-Wittig reaction of isocyanates with iminophosphoranes or by dehydration of urea [26]. Molina et al. previously reported the

• synthesis of 2-aminopyridine derivatives through an electrocyclization of conjugated carbodiimides derived from an aza-Wittig reaction of iminophosphoranes and isocyanates [27]. Hibino and co-workers also achieved the preparation of mutagenic amino-α-carbolines (2-amino-9H-pyrido[2,3-b]indole, AαC) and

• MeAαC by the electrocyclization of 3-alkenyl-2-carbodiimidoindole derivatives obtained by an aza-Wittig reaction of indol-2-yl-iminophosphoranes and isocyanates [28]. In this work, we report the first total synthesis of trigonoine B (1) involving the construction of a pyrrolo[2,3-c]quinoline framework

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• , it was transformed into (E)-vinylboronate (+)-145b in perfect stereoselectivity by using the recently developed boron-Wittig reaction with bis[(pinacolato)boryl]methane (144) [79]. By applying the Corey–Fuchs dibromoolefination and followed by Pd-catalyzed hydrogenolysis under Uenishi's conditions

• [80], compound (Z)-(+)-143a delivered the bromodiene (Z,Z)-(+)-145a in good yield and stereoselectivity. Isomerization of (Z)-(+)-143a to (E)-(+)-143b was carried out successfully using sterically hindered base DBU or DABCO. Treatment of (E)-(+)-143b with 144 using the boron-Wittig reaction [79

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• ). A Wittig reaction with pentylphosphonium bromide resulted in bromoalkene 21 in a 9:1 Z/E-mixture. In the following step, the Grignard reagent of 21 was converted into the respective Gilman cuprate with Cu(I)I for the selective reaction with the epoxide function of (S)-22 [34]. The hydroxyester 23

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• relatively short list: the reduction of the OH group of the C(CF3)2OH moiety (this protocol was employed in the synthesis of enantiomerically pure (S)-5,5,5,5',5',5'-hexafluoroleucine [1]); the Wittig reaction of Ph3P=C(O)C(O)OR with hexafluoroacetone, followed by the hydrogenation of the CH=C(CF3)2 unit

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• context, their journey started from syn-tris(oxonorborneno)benzene 23, obtained via palladium-catalyzed cyclotrimerization of iodonorbornene. The C3-symmetric compound 23 was then converted into the methylene groups containing compound 103 using Wittig reaction which on further treatment with

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• the target compounds required the prior preparation of a panel of variously substituted 1,4-diketones 5. The 1,4-diketones 5 have been prepared either by a Nef reaction [56] from the corresponding nitroenone 3 or a Wittig reaction [57] from 1,2-cyclohexanedione and the corresponding ylide 4 (Scheme 2

• route remains limited in terms of chemical diversity as it depends on the availability of the corresponding nitro derivative. It was thus decided to move on to the Wittig reaction [57], offering a much more straightforward and efficient route to a panel of new diketones, 5e–k, from 1,2-cyclohexanedione

• and the corresponding Wittig ylides 4a–g (readily accessible from the corresponding halogenated derivatives, Scheme 2). Indeed, the Wittig reaction leads exclusively to the isomerized products 5. With the 1,4-diketones 5 in hand, we first investigated the synthesis of indole and indolone derivatives

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• , GlaxoSmithKline disclosed a route to a fluoropyrrolidine 6 using a Wittig reaction between phosphonium salt 4 and aldehyde 5 [2]. The synthesis of phosphonium salt 4 (itself requiring 6 steps including partial saturation of a 1,8-naphthyridine moiety) and the formation of the triphenylphosphine oxide byproduct in

• integrin inhibitors. Commonly used synthetic routes to tetrahydro-1,8-naphthyridine moieties by hydrogenation of saturated naphthyridines 3. Previous synthetic route to fluoropyrrolidine 6 utilising a Wittig reaction and the novel, higher yielding route using a Horner–Wadsworth–Emmons reaction. Synthesis