Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• Suginome’s reagent along with LiCl, which completely overrode the need for a Grignard reagent and led to good chemical yields of the desired product (e.g., 272). In one case examined, a bulky silyl Grignard reagent gave the linear silyl derivative selectively. In addition, a quaternary carbon bearing the

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

• reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an α-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst

• . Moreover, the reaction of α-bromocarbonyl compound 2 and an alkyne 4 possessing a carboxamide moiety undergoes tandem alkyl radical addition/C–H coupling to produce indolinone derivative 5. Keywords: copper catalyst; 1,3-enyne; functionalized quaternary carbon; indolinone; tandem alkyl radical addition

• related coupling reactions [2][3][4]. Although there are many reports on alkyne transformations, one recent development in this area has been the reaction of alkynes with tertiary alkyl electrophiles to produce functionalized quaternary carbon atoms via addition [5][6][7][8][9][10] or coupling [11][12][13

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• reaction to achieve spirocyclic pyrrolocyclopentenone derivatives. Specifically, the KA2 reaction was envisaged taking into account cyclic ketones, to install a quaternary carbon atom carrying the required 1,6-enyne moiety for the subsequent Pauson–Khand reaction, thus achieving the corresponding tricylic

• phenylacetylene (2) were taken into account for the optimization of the KA2 reaction conditions with allylamine, in order to attain a quaternary carbon atom containing suitable alkenyl and alkynyl appendages for subsequent Pauson–Khand intramolecular cycloaddition (Scheme 2). The KA2 reaction was assayed

• 3–39 possess lower tendency to stay in the rod side of the triangle, as compared to BB drugs, suggesting for these compounds a higher shape complexity, as due to the presence of quaternary carbon atoms introduced by the KA2 coupling reaction. The intramolecular Pauson–Khand cyclization proved to be

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• with the quaternary carbon atom of the acetyl group in position O-7 (Figure 3). The anomeric configuration of the acetolysis products was identified by the coupling constant for the correlation C-1–C-2–C-3–H-3ax ( = 1.6–2.2 Hz, see Supporting Information File 1) and indicated the β-anomer [12][13][14

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• 169 substituted with chiral auxiliaries to methyl vinyl ketone for stereoselective construction of the quaternary carbon centers in 170 (Scheme 54). While screening a number of chiral auxiliaries, the authors found that upon electrolysis under galvanostatic conditions at low temperature, the

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• DBE and thus requiring 1 to be tricyclic. The 1H and 13C NMR data also revealed the presence of one hydroxylated quaternary carbon (C-9), two aliphatic quaternary carbons (C-4, C-10), two oxymethines (C-1, C-6), one aliphatic methine (C-5), one oxymethylene (C-12), two aliphatic methylenes (C-2, C-3

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

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• 58.6) and C-8 (δC 38.2) confirmed the presence of a verbenone moiety and connected the methylpentenoic acid moiety to the quaternary carbon C-7, completing the planar structure of 1. Compound 1 is thus a bergamotene type sesquiterpene, containing a bicyclo[3.1.1] ring system as well as a 2-methylpent-2

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• 5/6 bicyclic sesquiterpene with the molecular formula C15H26O (Figure 1). Interestingly, compound 1 contained a quaternary carbon with two methyl groups, which is uncommon for the cyclization mechanism of sesquiterpenoids and needs further investigation. Compound 2 was purified as a white powder. 1H

• characterised as a 5/6 bicyclic sesquiterpene compound 1 oxygenated at C-11. Interestingly, esterified compound 1 was isolated during the product extraction process, suggesting an esterification reaction. It contained a quaternary carbon with two methyl groups, which is uncommon of the cyclization mechanism of

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• , 1.88, 2.65 and 3.77), which are typical resonances for sativene-type sesquiterpenoids. The NMR data for 1 were very similar to those for prehelminthosporol lactone (5) except for the replacement of a methine group (δC 32.1; δH 1.42) at C-9 in 5 with a hydroxylated quaternary carbon (δC 73.1) in 1. This

• quaternary carbon (δC 74.8) in 3. This suggested that 3 was the 6-hydroxy analogue of 5, which was further confirmed by detailed analysis of key 2D NMR correlations (Figure 2). The absolute configurations of the stereocentres in 3 were established to be identical to 1 and 2 based on the analysis of proton

• revealed the absence of ester and alkene resonances and the presence of three hydroxylated methylenes at C-12 (δC 62.2; δH 3.79 and 3.65), C-14 (δC 69.8; δH 3.90 and 3.36) and C-15 (δC 62.9; δH 3.77 and 3.47), and one hydroxylated quaternary carbon at C-2 (δC 88.1). This suggested 4 was related to 5, but

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• –8.07 ppm, the signal of vinyl carbon C4 at 166.8–171.9 ppm, and the signal of quaternary carbon C5 at 96.0–116.3 ppm. It is worth noting that 2,2-dichloro (A, B) and 2,2-diarylsulfanyl (F, G)-substituted cations exhibit down field shifted signals in the 31P NMR (δ 87.82–115.37 ppm) in comparison with

• spectrum for species E4. Apart from that, in 13C NMR spectra, the signals of quaternary carbon bearing two methyl groups in E2 and E4 are very close (δ 70.3–70.9 ppm, see Scheme 1). Contrary to that, the signal of this carbon for E2 is very much down field shifted (δ 96.1 ppm). This indicates that in

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• afford polysubstituted cyclopropanols (or cyclopropylamines) potentially bearing several diastereo- and enantiomerically enriched adjacent stereogenic centers, including quaternary carbon stereocenters, as single diastereo- and enantiomer from a simple precursor, it would certainly provide an additional

• when the same sequence of diastereoselective carbometalation/oxidation was performed on cyclopropenyl ester 1, the in situ-formed donor–acceptor cyclopropanol undergoes a selective ring-opening to provide the acyclic product possessing a quaternary carbon stereocenter [57]. As the enantioselective

• the oxidation of the cyclopropylcopper species proceeded equally well and gave the corresponding cyclopropanols possessing two adjacent quaternary carbon stereocenters (7i–r) in good yields and excellent diastereomeric ratios. Here again, the methyl, the alkyl group from the organometallic and the

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• sp3 quaternary carbon, three sp2 methines, and five sp2 quaternary carbons (Table 1). The typical resonances at δC 145.6, δC 113.0, δH/C 7.30/136.8, δC 123.4, δC 153.0, δH/C 6.71/116.8 revealed the presence of a 1,2,4,5-tetrasubstituted benzene ring, and the signals at δH/C 6.08/99.1, δC 154.2

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• relative configuration of the major epimer of 8 (Figure 3) was established on the basis of a cross peak in the NOESY spectrum that correlated the methyl group at C3 with a methylene proton adjacent to the quaternary carbon of the side chain at C3a. The configuration at C3, adjacent to a carbonyl group, is

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• TAN1251A, TAN1251C and TAN1251D [86]. Wardrop and Burge [87] reported a iodine(III)-mediated oxidative spirocyclization of hydroxamates 50. The azaspirans 51 containing quaternary carbon centers were synthesized in good to excellent yields on treating substrates 50 with PIFA (31) in dichloromethane

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

• containing α-quaternary carbon centers were efficiently converted into the corresponding acetates under mild reaction conditions [27]. Various functional groups, including bromo (2a and 2f), fluoro (2b), carboxyl (2e), nitro (2g), and ester (2h) groups, were all well tolerated, providing the corresponding

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• spiro[indoline-3,2'-pyrrolidine]-2,5'-diones, via a post-Ugi-domino transamidation/cyclization sequential process, has been achieved in three sequential steps utilizing a one-pot reaction protocol. The variation in carboxylic acid substrates allows for the generation of new chiral racemic quaternary

• carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles. Keywords: convertible isocyanides; lactams; molecular diversity; oxindoles; transamidation; Introduction The Ugi-multicomponent coupling reaction [1][2], followed by post-modification

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• substituted styrenes. The phenonium cation intermediate I4 contains two reaction sites on the ethylene bridge. Electron donation due to the lone pair on the oxygen atom of the internal tosyloxy group may weaken the bond between the tosyloxy-bonded carbon and the quaternary carbon in I4. The reaction of

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

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• analogue of streptopyrrolidine was accomplished in 65% overall yield. Keywords: azlactones; dimerization; diasteoreselective synthesis; kinetics; streptopyrrolidine analogue; Findings Azlactones have been acknowledged as a common nucleophilic reagent to introduce a quaternary carbon stereocenter in the α

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• one occurred with a quaternary carbon (C-12). It was hence evident that the methyl group is attached to the hydroxy-substituted C-12, which itself is further connected with C-11 and C-14. HMBC interactions from H-15a and H-15b to C-12 lend additional support for the placement of the latter. The

• singlets in the 1H NMR spectrum. They were positioned next to the quaternary carbon C-2 on the basis of HMBC interactions. Interpretation of 2D NMR data allowed an extension of this residue with CH-4 and CH2-5. Ultimately, a heteronuclear long-range correlation from H-4 to C-6 linked the two fragments to

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• tolerated. Alkylketone substrates were also successfully converted to 2-oxazolines. Installation of substituents on the tether led to facile formation of product 6m containing a quaternary carbon and compounds 6n and 6o but without any observed diastereoselectivity. Interestingly, the selectivity for 6o

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• hexahydropyrrolo[1,2-b]isoquinolone derivatives fused with benzene 10 that have pronounced three-dimensional features and potentially contain several quaternary carbon centers (Figure 2). The first aspect has been recently recognized [29] as a central principle in drug design ensuring effective interaction of

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• , which showed an important four-bonded interaction between the hydrogen of the methylene C(3)=CH- group and the quaternary carbon C(4a) (Figure 2). The carbon C(4a) was interconnected in the HMBC with 2 other three-bonded interactions with hydrogen H-C(8) and H-C(6), whereas for the 16d (SYN) isomer the

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• broad singlet. The double bond proton in 12c resonating at 6.94 ppm as a singlet shows strong correlation in the HMBC spectrum with the quaternary carbon atoms resonating at 132.3, 130.8, and 123.1 as well as with the tertiary carbon atoms (=CH) at 118.6 ppm (Figure 4). This information clearly shows

• that the double bond (CH=C) is located between the pyrrole nitrogen atom and the benzene ring (Figure 4). On the other hand, the methylene protons in 13c resonating at 4.26 ppm as a singlet shows strong correlation with the quaternary carbon atoms resonating at 137.2 and 135.2 as well as with the