α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• thus the sense of chiral induction for the 1,4-addition reactions reported in Table 2. Tandem 1,4-addition–aldol condensation reactions We then went on to consider tandem 1,4-addition–aldol condensation reactions (Scheme 6), which offer the interesting prospect of generating an all-carbon quaternary

• view, the reported protocols are relevant as they offer a new, direct and modular route to enantioenriched α-mono- and α,α-disubstituted β-amino acids (β2-amino acids and β2,2-amino acids), with, for the latter, the noteworthy stereocontrolled construction of an all-carbon quaternary stereocenter

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• compound 12. Meanwhile, Campaña, Morcillo, and co-workers converted the eight-membered ring 11 to nonagon-containing carbohelicene 14 through a single ring expansion reaction by treating 11 with TMSCHN2 (Scheme 2). By reacting with Tebbe’s reagent, compound 14 could be converted to all-carbon analogue 15

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• . presented their work on the asymmetric desymmetrization of cyclopentene-1,3-diones 5 (Scheme 3) [23]. Following the Cu(OTf)2-catalyzed conjugate addition of R2Zn, the enolate 6 was trapped by several aromatic aldehydes 7. These complex chiral cyclopentane derivatives 8 bearing all-carbon quaternary

• contains six contiguous stereogenic centers out of which four are all-carbon quaternary stereocenters. The authors have achieved the stereoselective synthesis of waihoensene for the first time with a 3.8% overall yield (15 steps) (Scheme 59). The construction of the triquinane core included a Cu-catalyzed

• of a synthetic chemist, the most remarkable feature of this structure is the highly substituted cyclopropane ring incorporating two all-carbon quaternary centers, while the whole structure contains 7 stereocenters. Xu et al. recently demonstrated their 13-step total synthesis of (−)-peyssonnoside A

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• -8-6-5] tetracyclic all-carbon system with 10 stereogenic centers (Scheme 15). This natural product was isolated from two Gentianella plant species, namely G. nitida and G. alborosea used in Peruvian traditional medicine. The first report of its synthesis was given in 2014 by Hog and co-workers [46

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• reactions constitutes one of the main pillars of organic synthesis [1]. In this respect, the all-carbon Nazarov cyclization of divinyl ketones represents a direct method for the synthesis of five-membered carbocycles [2][3][4][5][6][7][8][9]. Variants of the Nazarov cyclization with substrates bearing one

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 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

• the 6-5-5 tricyclic skeleton includes the mediation of Nagata reagent for constructing the C1 all-carbon quaternary centers and gold-catalyzed cyclopentenone synthesis through C–H insertion. Keywords: aberrarone; C–H insertion; gold; Pauson–Khand; total synthesis; Introduction Marine natural

• , including two all-carbon quaternary centers, together with the non-enolizable cyclic α-diketone moiety collectively render aberrarone as an attractive but challenging synthetic target. Its congener elisabanolide (2) with a lactone in the D ring shows their potential biosynthetic relationship [2]. These

• through the corresponding lithium enolate occurred from the convex face of the bicyclic ring system [37]. After these two continuous stereocenters were successfully installed, the expected challenging all-carbon quaternary center at C1 was constructed utilizing the Nagata reagent (Et2AlCN). By using this

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• ][26]. Donor–acceptor cyclopropanes constitute an easily available equivalent of all-carbon 1,3-zwitter-ions used in targeted synthesis of various alicyclic as well as carbo- or heterocyclic compounds [27][28][29][30]. The reactive synergy of the three-membered ring and the C–C bond polarization due to

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• . Noteworthy, this methodology demonstrated a wide substrate scope, namely reacting smoothly with all-carbon backboned substrates 36c, as well as being applicable to esters and tosylamides, proving it to be a powerful protocol for the synthesis of stereocontrolled tetrasubstituted alkenes. In 2017, Sweeney and

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

• as precursors of nucleophilic radical species in metal hydride hydrogen atom transfer reactions. This unique reactivity, combined with the wide availability of olefins as starting materials and the success reported in the construction of all-carbon C(sp3) quaternary centers, makes hydroalkylation

• ) [6], and the presence of all-carbon quaternary centers (Figure 1). The all-carbon quaternary center motif represents a challenge in modern organic synthesis due to the inherent steric issues associated with the formation of these particular C(sp3)–C(sp3) bonds [7][8][9][10][11][12][13]. A glimpse of

• ., styrene derivatives [17]) that produce hundreds of tons for polymer synthesis. The goal of this review is to demonstrate the utility of olefins as starting materials in the synthesis of all-carbon quaternary centers through hydroalkylation reactions. Only the hydroalkylation of unactivated olefins as

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• simple modification (temperature, catalyst loading) combined with the iterative addition of boronic acids (1 equiv immediately and 1 equiv after 3 hours) [49]. Following Stoltz's works [11][27][47][48][49][51][52], Stanley et al. published the first example for the formation of all-carbon quaternary

• boronic acids, there were enantioselectivities of about 90% ee and average to excellent yields of 43–97% (Table 36) [62]. This catalytic system worked for 3-unsubstituted enones but was much more powerful in the case of addition reactions to 3-substituted enones that lead to all-carbon quaternary

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• approach consisted of a 3,3-sigmatropic rearrangement to give an all-carbon quaternary center, a ring-closing alkene metathesis to give an 8-membered ring, and the use of a single enantiomer of p-menthane-3-carboxaldehyde to make two natural alkaloids of opposite configuration. Firstly, (+)-euphococcinine

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

• , stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all

• -carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020

• (inclusive). Keywords: all-carbon; cyclization; [3 + 2] cycloaddition; natural product synthesis; stereocenters; Introduction The highly-substituted, stereo-congested, five-membered carbocycle containing contiguous stereocenters is one of the most common structural features in many structurally complicated

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

• bowl structure as compared to the pristine buckybowls containing all-carbon atoms in their frameworks. In sharp contrast, deeper bowl structure (1.30 Å) was observed in the case of triazasumanene as compared to the pristine sumanene (1.11Å) since the C–N bond length (1.47 Å) is shorter compared to the

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• ). Meldrum’s acid and its derivatives are versatile reagents in organic synthesis that can be transformed into a wide range of compounds. In 2006, the group of Fillion described the highly enantioselective synthesis of all-carbon benzylic quaternary stereocentres via a conjugate addition of dialkylzinc

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• studied, leading to the expected 1,4-products in excellent yields and remarkable enantioselectivities. More recently, tremendous breakthroughs were achieved in this field, notably by the formation of all-carbon quaternary chiral centers [6] and the challenging 1,6-, 1,8-, or 1,10-selective addition to

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

• towards chiral 1,4-dicarbonyls bearing tertiary and all-carbon quaternary stereocenters via oxidative cross coupling of 2-acylimidazoles 85 with silyl enol ethers 86 (Scheme 32). Chiral Rh complex 87 was exploited as a Lewis acid catalyst for the purpose of activating the substrate towards anodic

• oxidation by raising the energy of the HOMO upon enolate formation. Upon constant current electrolysis of a mixture of 85 and 86 in an undivided ElectraSyn 2.0 cell in presence of 2,6-lutidine as an external base and catalyst 87, products with tertiary carbon stereocenters as well as all-carbon quaternary

Remarkable effect of alkynyl substituents on the fluorescence properties of a BN-phenanthrene

• Alberto Abengózar,
• David Sucunza,
• Patricia García-García and
• Juan J. Vaquero

Beilstein J. Org. Chem. 2019, 15, 1257–1261, doi:10.3762/bjoc.15.122

• fluorescence quantum yield of BN-phenanthrene seems to be a general effect, irrespective of its position. It should be noted that the introduction of ethynyl groups into the all-carbon phenanthrene skeleton results in a slight increase in the fluorescence quantum yields compared to that of phenanthrene [27

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

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• weaker as expected due to the dilution effect caused by the presence of the carbohydrate host, but in an expansion it is possible to discern the presence of almost all carbon resonances of fisetin, with exception of C8, which most likely overlaps with the signal of the C4 of γ-CD. Of note are two

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• stereoablative approach (Scheme 3) [22][23]. Deprotonation and elimination of the halide in oxindole (±)-8 leads to achiral azaxylylene intermediate 11, which is trapped with malonate nucleophiles to form all-carbon quaternary centers. The overall transformation is unusual since oxindoles are typically

• reaction was reported by Stoltz for the generation of enantioenriched all-carbon quaternary stereocenters from racemic allyl β-ketoesters (e.g., (±)-20 → (+)-23, Scheme 5) [29]. This particular reaction is especially unusual since the stereoablative step requires scission of a C–C bond at a quaternary

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• istope-labelled precursors (Scheme 30a) [164]. These experiments revealed that all carbon atoms of the heterocycle are derived from acetate or propionate units and that no amino acid is incorporated. The nitrogen thus originates from transamination. More detailed information about the mechanism became

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• recently gained immense importance. 2-Oxindoles having all carbon quaternary centres at the pseudobenzylic position are common structural scaffolds in many naturally occurring alkaloids of biological relevance [22][23][24][25]. These heterocyclic motifs especially exist in indole alkaloids with a wide

• equivalents iodine or NIS. Gratifyingly, it was found that a range of β-N-arylamido esters (3a–s) and β-N-arylamido ketones (3t–x) underwent intramolecular dehydrogenative coupling (IDC) under both conditions A and B to afford a wide range of 2-oxindoles (4a–x) having an all-carbon quaternary center in high

• shows that formation of a stabilized tertiary radical probably facilitates the IDC process for the syntheses of 2-oxindoles. However, if a tertiary radical is responsible for the oxidative process, then one would realize the formation of dimeric 2-oxindoles sharing vicinal all-carbon quaternary centers

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• transition metals to affect asymmetric enyne cycloisomerization [13][14][15][16][17][18][19][20][21][22][23]..In particular, Mikami has disclosed a palladium-catalyzed asymmetric enyne cycloisomerization where a tetrahydrofuran containing a quaternary, all-carbon stereocenter is created in excellent yield

• asymmetric ruthenium-catalyzed cycloisomerization reactions in the literature. In 2011, our research group disclosed the ruthenium-catalyzed redox bicycloisomerization of 1,6- and 1,7-enynes to construct structurally complex [3.1.0] and [4.1.0] bicycles containing vicinal, quaternary all-carbon stereocenters

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• crucial for the reactivity by forming hydrogen-bond interactions with CPA. Ma and co-workers described the CPA (cat. 32)-catalyzed enantioselective decarboxylative alkylation of β-keto acids with 3-hydroxy-3-indolyloxindoles, affording the 3-functionlized 3-indolyloxindoles bearing an all-carbon

• -indolylmethanols through the hydrogen bond activating mode, which incorporated the 3-hydroxy-3-indolyloxindoles and o-hydroxystyrenes into the 3-allyl-3-indolyloxindoles, featuring one all-carbon stereogenic center and a (Z)-C=C bond. All products were obtained in excellent enantioselectivity (up to 97% ee) and (Z