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

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• between H10A and H3A observed in the experimental NOESY spectrum (Figure 6) allows the assignment of the configuration (S)-3A (with H3A in exo position) to compound 2. The attribution was further confirmed by comparing the calculated chemical shifts for all carbon and hydrogen atoms with the experimental

(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

• enantioselective synthesis of 3,4-dihydrocoumarins 150 bearing an all-carbon spiro-quaternary stereocenter utilizing Takemoto’s organocatalyst 77 (Scheme 48) [69]. The domino process is initiated by a Michael addition followed by acetalization, and subsequent PCC oxidation in an one-pot transformation. In 2012

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• processes Asymmetric oxidative coupling All carbon quaternary centers are prevalent in both natural and pharmaceutical compounds, but rank amongst the hardest to synthesize in a stereoselective manner. Dixon and co-workers have addressed this through the development of an asymmetric organocatalytic

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• of a dipeptide phosphine catalyst, a wide range of highly functionalized cyclopentenes bearing an all-carbon quaternary center were obtained in moderate to good yields and with good to excellent enantioselectivities. Keywords: [3 + 2] annulation; α-substituted allenoate; dipeptide phosphine

• -sulfonylimines proceeded in an unexpected [3 + 2] annulation mode to afford a cyclopentene ring with an all-carbon quaternary center (Scheme 1) [48]. In recent years our group has developed a family of amino acid-derived bifunctional phosphines and has intensively investigated related asymmetric transformations

• reactions yielded highly functionalized cyclopentenes with an all-carbon quaternary center in moderate to good yields and good to excellent enantioselectivities. Further extension of the reaction reported herein and mechanistic studies are ongoing in our laboratory. Experimental General procedure for the [3

Polydisperse methyl β-cyclodextrin–epichlorohydrin polymers: variable contact time ¹³C CP-MAS solid-state NMR characterization

• Isabelle Mallard,
• Davy Baudelet,
• Franca Castiglione,
• Monica Ferro,
• Walter Panzeri,
• Enzio Ragg and
• Andrea Mele

Beilstein J. Org. Chem. 2015, 11, 2785–2794, doi:10.3762/bjoc.11.299

• of D3 is shown in Figure 5), and native CRYSMEB to test the applicability of this measurement to the samples. The CP build-up curves for all carbon atoms of CRYSMEB are reported in Figure 6 and the results observed for the polymers D1 and D3 are shown in Figure 7 as an example. In all cases the

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• (Scheme 16). In 2014, Cai et al. [46] applied the desymmetrization strategy to construct chiral cyano-bearing all-carbon quaternary stereocenters, affording 1,2,3,4-tetrahydroquinoline analogues in good yields and excellent enantioselectivities (Scheme 17). The same group also observed that achiral

• desymmetrization strategy. Construction of cyano-bearing all-carbon quaternary stereocenters. An unexpected inversion of the enantioselectivity in the asymmetric C–N coupling reactions using chiral octahydro-1H-indole-2-carboxylic acid as the ligand. Differentiation of two nucleophilic amide groups. Synthesis of

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• obtained by ring-closing methods [29][30]. To extend our previously reported DYKATs beyond all-carbon electrophiles we decided to examine 3-chloro-3,6-dihydro-2H-pyran (2a, Scheme 1b). This was envisaged to be a challenging substrate. The presence of oxygen in the ring would modify the electronics, and

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• /L13) resulted in a surprising inversion of the regioselectivity. Indeed, the addition of ethylmagnesium bromide onto cyclic dienones occurred at the 1,4-position, affording compounds featuring an all-carbon quaternary center. The authors suggested that the chelating hydroxyalkyl chain was at the

Interactions between tetrathiafulvalene units in dimeric structures – the influence of cyclic cores

• Huixin Jiang,
• Virginia Mazzanti,
• Christian R. Parker,
• Søren Lindbæk Broman,
• Jens Heide Wallberg,
• Karol Lušpai,
• Adam Brincko,
• Henrik G. Kjaergaard,
• Anders Kadziola,
• Peter Rapta,
• Ole Hammerich and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2015, 11, 930–948, doi:10.3762/bjoc.11.104

• , but the interaction can here also be increased by “doubly-bridging” them [13]. Those redox groups that have shown the best interaction along the all-carbon bridges are the organometallic metal centres Re(NO)(PPh3)Cp* [24], Ru(dppe)Cp* [25], and Fe(dppe)Cp* [26] (Cp* = 1,2,3,4,5