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

• carbon center. In the first report on the total synthesis of simonsol C (Scheme 1), in 2016 Banwell’s group employed an intramolecular Heck reaction as key step to furnish the aryl-containing quaternary center and simultaneously construct the benzofuran skeleton [7]. This synthesis involved a total of 12

• simonsol C, two reports have utilized alkaline dearomatization strategies and another report used an intramolecular Heck reaction as the key reaction [5][6][7]. However, there have been no reports or studies utilizing acidic dearomatization, which is also effective, to synthesize an arylated quaternary

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

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

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

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

• install a quaternary carbon center connected to α’-methoxy-γ-pyrone therefore rely exclusively on the electrocyclization of tetraenes. With recently demonstrated potent antitumoral [25] and anti-HIV properties [26], aureothin is a natural product featuring the α’-methoxy-γ-pyrone motif connected to a

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• for the synthesis of 1,4-dihydroquinoline 129 possessing a quaternary carbon center from 128 [93]. The reaction was reported via a seven-membered bicyclic hemiaminal as mentioned in the mechanism. This catalytic rearrangement protocol was successfully applied for the construction of complex carbon

• Yamamoto et al [116]. The catalytic pathway was proved to involve the direct H-transfer to the vinylmercury complex from the aromatic ring. It involved Hg(OTf)2-catalyzed cyclization of aryl 1,1-disubstituted allenes with the formation of a quaternary carbon center followed by the formation of a cationic

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• reactions an ideal platform for the synthesis of molecules with increased molecular complexity. Keywords: hydroalkylation; hydrogen atom transfer; quaternary carbon center; radical addition; unactivated olefins; Introduction Natural product structures remain some of the main sources of inspiration for the

• the relevance of this moiety was given by Overman in 2014 [14], who stated that about 12% of the 200 most predicted drugs in the U.S.A. in 2011 had at least one quaternary carbon center, but this center was not synthetically constructed in any of them. Interest is currently growing in increasing the

• ]/AgClO4 as a catalyst system and reported the hydroalkylation of tethered alkenyl ketones 19 (Scheme 11) to obtain functionalized cyclic compounds (Scheme 11) [44]. Among the products, two examples of quaternary carbon center syntheses (20a and 20b) were both obtained in good yields. Products from the

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• unsymmetrical 3,3'-diindolylmethanes (DIMs) with a quaternary carbon center has been developed via iodine-catalyzed coupling of trifluoromethyl(indolyl)phenylmethanols with indoles. In contrast to previously reported methods, the new procedure is characterized by chemoselectivity, mild conditions, high yields

• ]. However, synthetic methods for efficient synthesis of unsymmetrical 3,3'-DIMs with a quaternary carbon center, including trifluoromethyl-substituted 3,3'-DIMs, are still rare. Sasaki et al. reported the reaction of trifluoromethyl(indolyl)phenylmethanols with indoles in the presence of trifluoroacetic

• substrate scope and functional group tolerance is highly desirable. As part of our continuous efforts to prepare biologically active DIM derivatives [38], we herein report an innovative approach to synthesize unsymmetrical 3,3'-diindolylmethanes (DIMs) with a fluoromethyl-containing quaternary carbon center

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• in biologically significant natural products. Natural product synthesis featuring the all-carbon [3 + 2] cycloaddition. (Quaternary carbon center(s) created by all-carbon [3 + 2] cyclization are highlighted in cyan; quaternary carbon center(s) created that are removed by subsequent transformations

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• addition (ATRA) [21] (Scheme 1, i–iii). Therefore, we postulated that if we could control the reactivities of the alkynyl–Cu and ATRA adducts, a tandem tertiary alkylation followed by an alkynylation could occur to produce a 1,3-enyne possessing a quaternary carbon center with good regio- and

• methodology can realize a Pd-free catalyst system to prepare complex quaternary carbon atoms. Herein, we report the Cu-catalyzed control of the reactivity of an alkyne (addition and coupling) undergoing tandem tertiary alkylation and alkynylation to produce a 1,3-enyne containing a quaternary carbon center

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• stereochemically stable quaternary carbon center [1]. For example, TAA-derived peptides containing a cyclopropane ring and ʟ/ᴅ-dimethyl tartrate showed an α-turn and form 310-helical conformations in higher oligomers [2][3][4]. While, TAA-derived peptides having a tetrahydrofuran ring demonstrated a β-turn type

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• applications have not been explored. We recently reported on the decarboxylative Ritter-type amination of carboxylic acids containing an α-quaternary carbon center using a combination of PhI(OAc)2 and I2 to produce the corresponding α-tertiary amine derivatives (Scheme 1) [25]. Mechanistic investigations

• reaction, namely acetoxylation, via the oxidative displacement of an iodine atom of the in situ generated alkyl iodide by PhI(OAc)2 [26]. Herein, we report on the decarboxylative acetoxylation of carboxylic acids that contain an α-quaternary carbon center using PhI(OAc)2 and I2 in a CH2Cl2/AcOH mixed

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• -catalyzed trifluoromethylation of N-aryl acrylamides using Langlois’ reagent (CF3SO2Na) as a trifluoromethyl source and water as the reaction medium (Scheme 36). A variety of CF3-containing oxindoles bearing a quaternary carbon center were formed under this conditions. Furthermore, more CF3SO2Na (3.0 equiv

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• ), their unique architecture is characterized by an ester-linked bromopyrrole carboxylic acid and a tetrahydropyrimidine ring in which one of the amino groups is attached to a quaternary carbon center. Due to their intriguing structures in combination with the promising biological properties this class of

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• proceeded in good to excellent yield and excellent enantioselectivity for almost all of the substrates that were tested. This methodology was further extended in the total synthesis of (−)-mesembrine. This natural product contains a sterically hindered and arylated quaternary carbon center, which was

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• corresponding propargylamines 7 containing a quaternary carbon center [37] (Scheme 8). Aliphatic alkynes and acyclic amines gave the corresponding products in low yields, whereas the methodology was ineffective for aromatic ketones. Gold-catalyzed A3-MCRs were also applied with the aim to functionalize

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• ; iodoaryl allyl azides; tandem radical cyclization; Introduction 4,4-Spirocyclic oxindole γ-lactams containing a quaternary carbon center are key structures for the synthesis of biologically active natural products and the related analogues [1][2][3][4]. Therefore, the development of an efficient synthesis

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• ]thiophenium salts have also demonstrated high ability for trifluoromethylation of β-ketoesters and dicyanoalkylidenes to yield the trifluoromethylated products with a quaternary carbon center, even if the substrates have a rather unreactive acyclic system. In this review, we wish to briefly provide a