The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• nucleophiles [27][28][29][30]. Thionaphthols, however, are overlooked in sulfa-Michael addition reactions. And to our best knowledge, no study is present concerned with SMAs with naphthalene-1-thiol as the nucleophile for the addition to enones. Encouraged by the good results obtained with enantioselective

• sulfa-Michael additions of thiols to chalcones with sulfonamide-type organocatalysts in the literature [30][31], in this study, a new quinine sulfonamide organocatalyst derivative was developed to catalyze the enantioselective SMA of naphthalene-1-thiol to trans-chalcones under mild conditions and with

• conclusion, we report the enantioselective organocatalytic sulfa-Michael addition reaction of naphthalene-1-thiol to trans-chalcones, in the presence of a new bifunctional quinine derived sulfonamide organocatalyst. The adducts obtained with moderate to excellent ee values are β-naphthyl-β-sulfanyl ketones

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• et al. managed the enantioselective arylation of aromatic trifluoromethyl ketones 150 with (S)-TRIP (Scheme 37) [96]. A variety of CF3-substituted enantioenriched benzylic alcohols 61 were thus synthesized after the trapping of protonated CF3-substituted ketones 134 (Scheme 37). Interestingly, these

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• enantioselective functional group interconversions on prochiral or racemic difluorocyclopropane and difluorocyclopropene derivatives have provided important ways of obtaining enantiomerically pure cyclopropanes. The key reactions in this context are the enzyme-catalyzed formation and hydrolysis of esters and the

• smooth hydrolysis. Wang et al. reported the enantioselective biotransformations of geminally difluorinated cyclopropanecarbonitriles and amides in 2004 [77]. They transformed gem-difluorocyclopropane derivatives with the help of a soil microorganism, Rhodococcus sp. AJ270, which provided a very effective

• biotransformation of gem-difluorocyclopropanecarboxamide (±)-83 (Scheme 34) occurred rapidly and under mild conditions to give (1R,3R)-amide 83 (46% yield, >99% ee) and (1S,3S)-acid 82 (51% yield, 87 % ee). Enantioselective hydrogenation of difluorocyclopropenes: Recently, Mikami and co-workers reported the

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• very low, this work certainly established the basis for the future enantioselective syntheses of inthomycins and related natural products. In 2002, Moloney et al. described an efficient synthetic route using the Stille coupling reaction as the key step to accomplish the synthesis of phenyl analogues of

• )-diene 66 (E/Z = 19:1, separable) using the standard (E)-selective Horner–Wadsworth–Emmons (HWE) reaction. DIBAL-H reduction of ester 66 followed by MnO2 oxidation produced aldehyde (E,E)-67 stereoselectively. Unfortunately, attempted enantioselective aldol reactions of (E,E)-67 with silylketene acetal

• using a four-step sequence such as Negishi’s (Z) and (E)-stereoselective isomerization of the terminal alkyne followed by iodinolysis [19][70][71], oxidation to the corresponding aldehydes and enantioselective Kiyooka–Mukaiyama aldol reaction followed by TES protection of the resulting alcohols (Scheme

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

• developed by the authors conferred an excellent methodology to obtain the 9-azabicyclo[3.3.1]nonane ring present in (±)-euphococcinine (2). Kibayashi synthesis – 2002 Kibayashi et al. performed the enantioselective synthesis of (−)-adaline (1). Their approach had as key steps SN2-type alkynylation

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• ethers of 3,6-diacetylcarbazole with p-benzoquinone (Scheme 1B) [49], the double Buchwald–Hartwig amination of 4,4'-biphenanthrene derivatives (Scheme 1C) [45] and a enantioselective Fischer indolization–oxidation protocol (Scheme 1D) [43]. Each method is not without drawbacks such as hardly available

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

• fragmentation to afford alkene 72 in 61% yield. Marcfortine B (8) was synthesized from alkene 72 in seven steps. The enantioselective synthesis of marcfortine C (9) commenced with a catalytic asymmetric cyano-substituted TMM cycloaddition of oxindole 73 and TMM donor 75 with Pd(dba)2/74 as catalyst to give a

• rearrangement product 99 in 85% yield. The synthesis of daphenylline (11) was completed by a seven-step synthesis from benzofuran 99. Phosphine-catalyzed enantioselective [3 + 2] annulation In 2019, Lu and co-workers disclosed a novel chiral-phosphine-catalyzed enantioselective [3 + 2] annulation of allenes and

• isoindigos to give an enantioenriched annulation adduct bearing vicinal quaternary stereocenters [46] (Scheme 7A). Both symmetric and unsymmetric isoindigos can undergo enantioselective [3 + 2] annulation with an allene and produced a chiral adduct with high yield and high ee value. When unsymmetric

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• selectivity factor of s = 2.0 and 1.87 for 7b and 8b, respectively. The above-mentioned results indicate that the binding cavity composed of two preorganised ureido groups and chiral alkyl substituents in the near proximity possesses some ability of enantioselective recognition. In fact, this assumption was

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• catalysis [33]. Final acetylation of the hydroxy esters delivered the target compound isoprenyl 3-acetoxyoctadecanoate (11). Comparison of mass spectra and retention index confirmed the identity of the naturally occurring compound and 11. An enantioselective synthesis of isoprenyl (Z)-3-acetoxyoctadec-13

• eluting ester is isoprenyl (Z)-3-acetoxy-13-octadecenoate, while the earlier eluting one is the 11-isomer. With optically active material in hand, the absolute configuration of 12 was determined by enantioselective gas chromatography. Because direct separation of the large esters seemed to be difficult

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• -lactone derivatives spiro-fused to an oxindole (A), one of which exhibited a potent cytotoxic activity [9]. Our research group succeeded the enantiopure synthesis of these compounds, in which enantioselective allylation of an isatin derivative with an amido-functionalized allylstannane was employed as a

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g., norsalvinorin or cacospongionolide B. Keywords: Diels–Alder reaction; enediyne; enyne metathesis; ring-closing metathesis; ruthenium precatalyst; Introduction Among the plethora of metathetic

• reactions of substrates containing three or more multiple bonds attracted special attention due to the applications in tandem metathesis processes [9][10] or stereodiscriminating enantioselective ring-closing metathetic reactions [11][12][13]. Apart from metathesis, enynes are also interesting substrates

• for other catalytic reactions, e.g., for the Pauson–Khand reaction [14]. In the enantioselective RCM, prochiral trienes have been most often employed, leading to chiral cycloalkenes. The Schrock molybdenum precatalysts [15][16][17] proved to be more effective than the Grubbs or Collins ruthenium

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• -Michael-type cycloadducts [28]. Very recently, a catalytic enantioselective (3 + 2) cycloaddition of diazabicyclohexanes with chalcones was carried out [30]. 1,5-Diazabicyclo[3.1.0]hexanes have been employed as precursors for 1,3-dipoles not only in (3 + 2) but also in (3 + 3) cycloadditions. It was shown

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• transformations [7][8][9]. Furthermore, the chiral nature of polysaccharides has also been used as a tool for enantioselective catalysis such as carbonyl hydrogenations and amino acid hydrolysis, proving the unique ability of these biomass-based supports [10][11]. Chitin is another type of biomass feedstock that

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• Kingdom 10.3762/bjoc.16.197 Abstract Enantioselective photocatalysis has rapidly grown into a powerful tool for synthetic chemists. This review describes the various strategies for creating enantioenriched products through merging enantioselective catalysis and photocatalysis, with a focus on the most

• recent developments and a particular interest in the proposed mechanisms for each. With the aim of understanding the scope of each strategy, to help guide and inspire further innovation in this field. Keywords: enantioenrichment; enantionselective catalysis; enantioselective photocatalysis

• ; photocatalysis; photochemistry; Introduction Enantioselective catalysis has become a central focus for organic synthetic chemistry, particularly since the Nobel prize was awarded to Sharpless, Knowles, and Noyori for their pioneering work in the field. In the last 15 years, photocatalysis has become a

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

• can not only be useful for enantioselective synthesis of π-bowls but also to produce novel building blocks for molecular switches, chemical machines, molecular motor, ferroelectric memories, molecular devices, and sensory materials etc. Interestingly, electronic switching, thermal transport and

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• alkaloid-promoted electrophilic fluorination producing enantioenriched post-Ugi adducts fluorinated at the peptidyl position. Keywords: cinchona alkaloids; electrophilic fluorination; enantioselective synthesis; 2-oxo-aldehydes; Ugi reaction; Introduction Multicomponent reactions (MCRs) [1][2][3][4][5][6

• ], no general asymmetric protocol for the four-component mode has been developed until very recently. In 2018, Houk, Tan and co-workers described an efficient enantioselective procedure operating in the presence of catalytic amounts of chiral phosphoric acids (Table 2) [57]. Two synthetic protocols have

• previously tested the reactivity of 8 in the intermolecular aldol addition to ethyl glyoxalate [62]. As these attempts met with failure, we have turned our attention to enantioselective fluorination reactions [63][64][65]. Specifically, we decided to explore the enantioselective electrophilic fluorination of

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• developing a robust strategy in regards to the potential application of our route to the production of other lipid A analogs. Results and Discussion The acyl chain (R)-3-(2-naphthylmethoxy)tetradecanoic acid 7 was prepared via an enantioselective route as previously reported (Scheme 1) [16]. Lauroyl chloride

• (3) was treated with Meldrum’s acid (2,2-dimethyl-1,3-dioxane-4,6-dione) followed by decarboxylation in methanol to give methyl 3-oxotetradecanoate (4) in 77% yield. The enantioselective hydrogenation of the β-carbonyl group using (R)-Ru(OAc)2(BINAP) at 65 °C and under 1.5 MPa H2 afforded methyl (R

• the 4′-OH group. This work is currently underway in our lab. Chemical structures of hexa-acylated Escherichia coli lipid A, monophosphorylated lipid X (the reducing monosaccharide lipid A precursor), and disaccharide lipid A precursor (“disaccharide lipid X”). Enantioselective synthesis of Nap

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• reported in 2005 by the Akiyama’s group [16]. This work clearly demonstrated the potential of these catalysts in enantioselective transformations. An additional important point of this work was the use of enantiopure tartaric acid as a precursor for the catalyst preparation being a conventional natural

• yield and enantioselectivity of the reaction dropped dramatically, hence confirming our initial proposal that the free hydroxy groups in the chiral phosphoric acid 3 played an important role in this enantioselective transformation. Based on these results, a plausible transition-state structure was

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• moderate to good yield as a single diastereoisomer. Keywords: enantioselective catalysis; formal [2 + 2] cycloaddition; N-heterocyclic carbene; ring opening; trifluoromethyl group; Introduction The trifluoromethyl unit holds a prominent and privileged position within organic chemistry [1][2][3][4][5][6

• practical methodologies capable of the enantioselective incorporation of the trifluoromethyl unit into organic molecules has been developed widely [10][11][12], with a series of elegant organocatalytic strategies utilized toward these aims [13]. One general strategy for the organocatalytic construction of

• stereogenic trifluoromethyl centers is through enantioselective addition of enolates or their equivalents to prochiral trifluoromethyl ketones (Figure 1A). Within this area, a common catalytic approach has utilized aliphatic ketones as enolate equivalents using prolinamide, cinchona, or hybrid catalysts that

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• and co-workers reported an excellent thiyl radical-catalyzed enantioselective cyclization reaction of vinylcyclopropanes with alkenes [7]. For the extension of this concept, in 2018, Miller and co-workers reported a UV-light-promoted disulfide-bridged peptide-catalyzed enantioselective cycloaddition

• peptide-catalyzed enantioselective cycloaddition. Disulfide-catalyzed [3 + 2] methylenecyclopentane annulations. Disulfide as a HAT cocatalyst in the [4 + 2] cycloaddition reaction. Proposed mechanism of the [4 + 2] cycloaddition reaction using disulfide as a HAT cocatalyst. Disulfide-catalyzed ring

• disulfide-catalyzed enantioselective synthesis of ophirin B. Disulfide-catalyzed isomerization in the total synthesis of (+)-hitachimycin. Disulfide-catalyzed isomerization in the synthesis of (−)-gloeosporone. Acknowledgements I thank Prof. Xiao Wang (Nanjing University) for helpful discussions. Funding I

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

• acceptors in highly enantioselective C–C bond-forming reactions with organometallics. The work highlighted in this minireview is divided into two sections, based on the position where the bond is formed. The first part focuses on acceptors in which the reacting unsaturated double bond is embedded into the

• enantioselective methods for the synthesis of these compounds resulting in high yield and enantioselectivity has proven challenging. As a result, significant effort has been invested into copper-catalysed asymmetric conjugate addition reactions using organometallics. In 2005, Feringa and co-workers reported on the

• aluminium reagents and commercial alkylaluminium reagents were examined in this methodology, providing the corresponding products with a moderate yield but high enantioselectivity (Scheme 2B). In 2009, Feringa and co-workers presented the first highly enantioselective 1,2-addition of dialkylzinc reagents to

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• enantioselective and chemoselective oxidations of many organic compounds. Notably, the Gryko’s group recently described an enantio- and diastereoselective approach involving a porphyrin-based photooxygenation of aldehydes with sequential reduction to yield chiral diols in yields up to 91% and significant er (up to

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• precursors affords both enantiomers Δ-10 (from CuClO4) and Λ-10 from (Cu(CH3CN)4PF6). UV–vis and circular dichroism spectroscopic studies evidence that the helical chirality exhibited by these two catalysts could be reversed by redox stimuli. These complexes could perform enantioselective Michael addition

• trifluoromethylation of heteroaromatics with redox-active iminosemiquinone ligands. Reversal of helical chirality upon redox stimuli and enantioselective Michael addition with a redox-reconfigurable copper catalyst. Interaction of guanidine-copper catalyst with oxygen and representative coupling products. a4 mol

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• ][4]. A heterocyclic ring containing a P atom appears in many popular P(III)-ligands, such as BPE, DuPhos, TangPhos, DuanPhos, ZhangPhos [5][6][7][8][9][10][11], among which a number of species may be considered as privileged ligands for transition metal-catalyzed enantioselective transformations [12

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• ) as the final product. Kempene diterpenes The first enantioselective synthesis of kempene diterpenes 14a–c, natural compounds exhibiting a significant antibiotic activity against B. subtilis, relying on the domino enyne metathesis of the adequate dienyne precursors as a key step, was disclosed by Metz