Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• tertiary enamides as cyclization precursors (Scheme 6). The analogous polycyclization generated a tetracyclic N-heterocycle with three continuous stereogenic centers, one of them being an aza-quaternary carbon [31]. The resulting fused ring-system structurally resembles the nucleus of erysotramidine

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• simultaneously installing the hydroxy group at C30. The latter intermediate could in turn be derived from dienone 11 by an AcOH-interrupted Nazarov cyclization [32][33][34], thereby establishing the B ring with the desired all-cis stereochemical configuration, including the quaternary carbon at C10 and the

• 4.4:1 mixture of regioisomeric alcohols with the desired isomer being the major component, presumably due to the considerable steric hindrance from the quaternary carbon at C4. However, decagram-scale separation of these two isomers by chromatography proved troublesome. Fortunately, the distinct

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• influence of steric and electronic effects during the hydrometallation process, simultaneously achieving the synthesis of chiral α-quaternary carbon amino acid derivatives 26 and α-chiral β-amino acid derivatives 27. Using a copper catalyst, the chiral α-quaternary carbon amino acid derivatives 26 were

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• quaternary centers that contain functional groups is challenging mainly because of their sterically demanding property [9][10][11]. In this context, the incorporation of cyano groups at the quaternary carbon centers is promising for the development of versatile acyclic all-carbon quaternary stereocenters

• with diverse functional groups [12][13][14]. Consequently, the development of selective and predictable strategies for the introduction of cyano groups into quaternary carbon frameworks has become necessary in organic synthesis. The transition-metal-catalyzed hydrocyanation of carbon–carbon double

• catalytic hydrocyanation of alkenes [22], including the industrially relevant DuPont adiponitrile process from 1,3-butadiene using nickel catalysts [23], the hydrocyanation of allenes to produce functionalized β,γ-unsaturated nitriles with quaternary carbon centers has not been investigated extensively [24

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• moiety are non-linear with a Ca–N–C angle of 100°. Due to the stereospecificity of the reaction, racemization would have to occur already in 9 through a topomerization (e.g., similar to a Berry pseudorotation) of the metal complex, considering that species with a quaternary carbon, as they appear in

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

• synapse growth and inhibits acetylcholinesterase. (±)-Simonsol C (Figure 1) has received considerable attention due to the presence of an aryl- and allyl-containing quaternary carbon center, which is common in natural products such as galanthamine and morphine. To construct the quaternary carbon in

• ] and has been used in syntheses of natural products containing aryl quaternary carbon centers [9][10]. Unlike the intramolecular alkylation strategy of a phenol derivative, which can only be applied in basic dearomatization reactions, our approach using an α-iodophenol ether as precursor of the

• route to date. The structural motif of an all-carbon quaternary center containing an aryl group is common in many natural products, such as galanthamine and morphine. Our current strategy provides an alternative approach for the synthesis of aryl-containing quaternary carbon centers, which could be

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• spectrum of 7a, a correlation of the NH proton with the bridging carbon atoms C(3a'), C(9b'), and the quaternary carbon atom C(1') of the indolenine fragment is observed with δH 136.6 ppm, 134.0 ppm, and 53.6 ppm, respectively (Supporting Information File 2, Figure S20). The most important HMBC

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• enantioselectivity. Furthermore, a lactam containing a quaternary carbon center (2g) was prepared. However, a lower enantioselectivity was observed for product 2h due to the similar steric environment of the two alkyl substituents. As shown in Figure 1, a catalytic cycle was proposed for the intramolecular C–H

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• , Mei and co-workers reported a chiral phosphoric acid-catalyzed asymmetric intermolecular formal (3 + 2) cycloaddition of azoalkenes 53 with azlactones 15 (Scheme 28). This methodology provides fully substituted 4-pyrrolin-2-ones 78 bearing a quaternary carbon atom in high yields (72–95%) and

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

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• functional handles for further elaboration. Notably, tertiary arylacetic acids can also be well tolerated to yield nitriles with quaternary carbon centers in good yields (17 and 18). Simple carboxylic acids without functional groups at the alpha position to stabilize the corresponding carbon centered

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• minor products as well (7–20% yields). The formation of biphenyls 44 can be explained by 1,4-addition and ring-cleavage to give intermediate AH, aldol reaction (intermediate AI), migration of the ester group from the quaternary carbon to the phenolic oxygen atom (intermediate AJ) and aromatization. The

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• methyl groups at δH (0.83, 0.87, 0.98 and 1.77). Its 13C and DEPT NMR spectra showed 15 carbon resonances, including four methyl groups, four methylenes, four methines, and three quaternary carbon atoms. This information suggests that it may be a drimenol congener and the structure was further supported

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• the orange plates of compound 4c belonged to the monoclinic P21/c group. Due to the asymmetry of the quaternary carbon atom adjacent to the carbene center, the latter compound crystallized as a racemic mixture. Solutions of MIC·CS2 zwitterions 6a–f in CD2Cl2 or CDCl3 employed for NMR analyses were

• contrast with the most common cyclization processes leading to imidazol(in)ium derivatives, which afford symmetrical products with identical substituents on both nitrogen atoms [82]. Although cyclic aldiminium salts are less readily available, they feature a quaternary carbon atom next to the carbenoid

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• ]. Importantly, these methodologies could also be smoothly extended to the synthesis of isoquinolinediones, which borne a quaternary carbon center. Furthermore, Yatham and his colleagues unveiled the first NaI/PPh3-mediated photocatalytic decarboxylative cascade cyclization of 2-isocyanobiaryls 44 with alkyl N

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• -workers [61] extended the application of NHC–copper catalysts to the conjugate addition of boronates to acyclic α,β-unsaturated carboxylic esters, ketones, and thioesters leading to the enantioselective formation of boron-substituted quaternary carbon stereogenic centers (Scheme 43). All transformations

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

• compound 8b revealed only a single signal of a carbonyl carbon at 193.2 ppm, and a signal of a quaternary carbon at 167.0 ppm, which could not be assigned. These spectral data prompted us to reconsider the structure of compound 8b. The reaction of chlorinated nitrostyrene 2b with acetylacetone (3b) was in

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• lactam 2 structure involving the replacement of a quaternary carbon carrying two electron-donating methyl groups with an electron-withdrawing carbonyl group (2b → 3). The starting isoquinoline-1,3(2H,4H)-dione was prepared [31] from homophthalic acid and then brominated with NBS to give 4

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• can operate as an efficient photoredox catalyst, providing an economical access to construct important oxindole scaffolds containing a quaternary carbon center. This synthetic method features a broad substrate scope, good functional group tolerance and operational simplicity. Mechanistic

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• consecutive all-carbon quaternary carbon atoms [54][55][56]. Preliminary biological screening of this family revealed notable antibacterial and anticancer activities due to the α-methylene lactone moiety they bear [57]. Recently, in order to synthesize the common core present in crinipellins, Xie and Ding’s

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• ’-methoxy-γ-pyrone in one step. To construct the quaternary carbon of the 2,5-cyclohexadienone of the target, a strategy based on the Robinson-type annulation of an aldehyde derived from α-crotyl-α’-methoxy-γ-pyrone was applied. The grafting of the simplified target’s side chain was demonstrated through an

• oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation

• ; Introduction The α’-methoxy-γ-pyrone motif is present in natural products and bioactive molecules [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Amidst these targets, a number contains a quaternary carbon vicinal to the scaffold, such as crispatene and photodeoxytridachione (Scheme 1a) [15]. These molecules

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• one quaternary carbon stereocenter and 1,2-dikeone moiety, Nazarov cyclization [33] of 7 was proposed for synthesizing this challenging moiety. The corresponding precursor cyclopentenone 8 may be prepared from alkynone 9 through a gold-catalyzed C–H insertion [34]. Alkynone 9 could be achieved through

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• displayed 26 carbon signals including two oxygenated carbons (δC 85.8 and 72.4), an oxygenated quaternary carbon (δC 79.5), and a glucopyranosyl unit (δC 101.9, 78.3, 77.7, 75.2, 71.9, and 63.0) (Table 3). These 1H and 13C NMR spectra of 4 were similar to those of ent-kauran-3α,12α,16α-triol except for an

• = 11.8, 5.7 Hz), 3.54 (1H, t, J = 9.3 Hz), 3.39 (1H, t, J = 9.3 Hz), and 3.28 (1H, ddd, J = 9.7, 5.7, 2.2 Hz)]. The 13C NMR spectrum of 5 displayed 28 carbon signals including two oxygenated carbons (δC 85.5 and 72.4), an oxygenated quaternary carbon (δC 79.6), a glucopyranosyl unit (δC 99.5, 75.7, 76.3

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• oxygenated sp3 secondary carbon (δC 76.3) and one oxygenated sp3 quaternary carbon (δC 74.2). As two of the six degrees of unsaturation were occupied by the double bond and carbonyl group, the remaining four unsaturations of 1 corresponded to a tetracyclic skeleton. The 1H,1H-COSY experiment (Figure 2

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• the basis of 2D NMR data. In the HMBC spectrum, the singlet methyl protons H3-17 and H3-18 show correlations to C-7, a quaternary carbon at 47.4 ppm (C-8), and an oxymethine carbon at 80.3 ppm (C-9). COSY and HMBC data established the alkyl chain from CH-9 to CH3-16. A correlation between H-9 and C-19