Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• synthesis of compounds with quaternary centers and natural products with high structural complexity. In 2014, Li et al. reported a CuCl2-catalyzed cross-dehydrogenation coupling reaction of C(sp3)–H bonds adjacent to an ether oxygen and the C(sp3)–H bonds at the α-position of a carbonyl functionality in the

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

• 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

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• quaternary centers is tackled by the direct cycloaddition of allyl cation 90 across a tetrasubstituted olefin 95, at the same time elaborating the cyclopentane core of this natural product. The completion of this short synthesis also nicely showcases the use of dihydrodithiinmethanol 90 as a synthetic

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

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

• of a double bond by increasing the Fsp3 with the concomitant formation of carbon quaternary centers. Olefins are desirable starting materials, as they are usually low-cost and stable chemicals that are readily available from natural sources (e.g., terpenes [3][4][5]) or from industrial processes (e.g

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

• -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

• , the all-carbon [3 + 2] cycloaddition can forge vicinal all-carbon quaternary centers [12] in a single-step operation and provides a direct access to various substituted five-membered carbocycles. These characteristics make the all-carbon [3 + 2] cycloaddition an appealing method and/or strategy in the

• % yield, which possesses three contiguous stereocenters with vicinal all-carbon quaternary centers. (Scheme 11A). According to the proposed mechanism, coordination of the triple bond of 142 to the electrophilic platinum complex A followed by intramolecular nucleophilic attack by the methoxy group gives

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• dialkyl effect associated with the quaternary centers [52]. Finally, it should be noted that a number of alkene containing phosphine boranes have been employed in metathesis reactions [53][54]. In particular, the tetraalkenyl diphosphine diborane 19·2BH3 in Scheme 10 represents a downsized version of 11

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

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• ring-closing metathesis (RCM) [24][25][26][27][28][29][30][31][32]. Whereas, the diallyl derivative 2 can be derived from a readily available Diels–Alder (DA) adduct 3 through an allylation sequence. Results and Discussion Installation of two C–C bonds to generate quaternary centers in a

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

• 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

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

• features in a variety of potent natural products and bioactive agents [1][2][3][4][5]. As exemplified by the marine natural products manzazidins A and C [2][3][4][5], they may be characterized by diverse configurations, including synthetically challenging quaternary centers. Owing to their pronounced

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

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• resulting in the broad uninformative NMR spectra in the cascade byproducts. The structure of 15 is unremarkable except for the presence of a highly elongated C–C bond (1.63 Å) brought on through the steric congestion of the adjacent quaternary centers. A similar situation has been reported [29]. The use of

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• quaternary centers, two of which are stereogenic. Being a hydrocarbon, (−)-thujopsene (10) has few natural handles for retrosynthetic analysis. Inspired by the complexity of this relatively small natural product, several total syntheses of racemic 10 have been reported [25][26][27][28][29] along with at

• quaternary centers. The medicinal relevance and structural complexity of vincadifformine have led to a large number of total syntheses [98][99][100][101][102][103][104], including several enantioselective examples [105][106][107][108]. Recently, Pandey reported a highly efficient synthesis of

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• activated isatin-based alkenes (Scheme 39) [76]. The reactions, performed in chloroform in the presence of molecular sieves at room temperature, provided biologically important 3-spirocyclopentene-2-oxindoles with two contiguous quaternary centers in very high yields and with good enantioselectivities; they

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• quaternary centers at the ring junction. We decided to start the sequence with known enone 15 [39] and intended to construct the all-carbon quaternary center at C13 by substrate controlled α-functionalization. The second quaternary center at C14 might be established by 1,2-addition and finally, ring-closing

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• potential drugs for the treatment of schizophrenia and alcohol addiction [34]. However, the synthesis of indole alkaloid derivatives containing a propellane ring system is a challenging task due to the presence of quaternary centers involved with these systems [35]. We envisioned a new synthetic route to

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• carbenes, guanidines, thioureas, amidinium ions, diols, and Brønsted acids showed their value to give densely functionalized Diels–Alder products in high selectivities [1][2][3][4][5][6][7]. In addition, some organocatalysts enabled even the formation of quaternary centers in Diels–Alder cycloadditions [3

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• the cycloadditions efficiently incorporated consecutive quaternary centers into the complex fused skeleton, overriding the considerable steric hindrance of the dipolarophiles composed of the tri- and even tetra-substituted olefin groups. To test the generality of the site-selective cycloaddition at

Gold(I)-catalyzed formation of furans by a Claisen-type rearrangement of ynenyl allyl ethers

• Florin M. Istrate and
• Fabien Gagosz

Beilstein J. Org. Chem. 2011, 7, 878–885, doi:10.3762/bjoc.7.100

• involves a Claisen-type rearrangement that allows the efficient creation of quaternary centers under mild experimental conditions. Keywords: Claisen rearrangement; furans; gold-catalysis; quaternary centers; Findings Furans represent an important class of heteroaromatic compounds, which are found in a

• ether substrates are easily accessible via various methods (see Supporting Information File 1 for more details), • the Claisen-type rearrangement would allow the formation of two new C–O and C–C bonds in a single step, • the reaction would allow the easy formation of quaternary centers and the

• employed and the easy formation of quaternary centers. The selectivity observed in the structure of the final product is in agreement with the postulated Claisen-type rearrangement. Further studies related to the development of an asymmetric version of this new gold(I)-catalyzed process and its application