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

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• when the “cyclisation” operation is achieved from geminal motifs (Figure 7B). Significant logP reductions are observed, especially from the internal geminal fluorination motif as in G9 to E2 (0.72 logP units). Starting from a trifluoromethyl group (Figure 7C), similar logP reductions are achieved (e.g

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• heteroarene 6.3. Other reductive fragmentations Another organophotocatalytic strategy for accessing C(sp3) radicals relies on the reductive homolytic cleavage of easily reducible functional groups. In this case, the substrates can act as acceptors in SET reductions, and the alkyl radical is obtained after the

• SET reductions to generate the corresponding radical anions (Scheme 21c). Organophotocatalysis has been successfully exploited to promote these SETs and access charged alkenyl and aryl radicals. The reduction of carbon–heteroatom double bonds is especially easy and leads to the formation of ketyl

• a suitable Michael acceptor 24.2 to obtain the corresponding allylation product 24.3 after a desulfonylation. Enones can also be subject to SET reductions through photoredox catalysis, and this can lead to [2 + 2] cycloadditions [2][108]. Similar intermediates can also be generated through 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

• functionalised alkyl chains at the β-position of the alkenylpyridines, the catalytic system also showed a high functional group tolerance, and thus allowing straightforward chemical transformations of the addition products, including, for example, reductions, cycloadditions, and coupling reactions (Scheme 15B

Bipyrrole boomerangs via Pd-mediated tandem cyclization–oxygenation. Controlling reaction selectivity and electronic properties

• Liliia Moshniaha,
• Marika Żyła-Karwowska,
• Joanna Cybińska,
• Piotr J. Chmielewski,
• Ludovic Favereau and
• Marcin Stępień

Beilstein J. Org. Chem. 2020, 16, 895–903, doi:10.3762/bjoc.16.81

• the previously reported cNMInEE series (n = 1, 2, 3) it was also possible to observe one reversible oxidation and four reductions, the first two being reversible [32]. The first oxidation potentials (EOx1) vary from 0.62 to 1.09 V, while the first reduction potentials (ERed1) range from −1.54 to −0.60

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• work of Stryker and co-workers on triphenylphosphine-stabilized copper hydride complexes [1][2], copper hydrides have been widely used for conjugate reductions of α,β-unsaturated carbonyl compounds [3]. Especially a chiral copper catalyst combined with a stoichiometric amount of a silane reagent, which

• both the reactivity and selectivity (Table 1, entries 7–10), while the replacement of the ethoxy groups of (EtO)2MeSiH with methoxy or trimethylsilyloxy groups resulted in only moderate reductions in the enantioselectivity and high yields. At the same time, trialkoxysilane (EtO)3SiH and polymeric

• reductions. The phenolic N-substituent of the chiral NHC ligand was essential for the high enantioselectivity. Good enantioselectivities were observed for the various (Z)-configured substrates with different β-substituents. Further investigations on the catalyst development based on this knowledge are

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• . The use of either homoleptic or heteroleptic complexes in atom transfer radical addition (ATRA) reactions, reductions, oxidations, proton-coupled electron transfer (PCET) reactions, and reactions based on energy transfer will be discussed. 1 Homoleptic Cu(I) complexes Homoleptic complexes based on

• can be readily obtained in a crystalline form. Herein, we will report their use in ATRA reactions, reductions, oxidations, as well as in PCET and energy transfer reactions. 2.1 ATRA reactions In 2015, Reiser and co-workers reported the synthesis of a novel copper-based heteroleptic complex bearing a

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

• summarized the background and recent advances and arranged this article to provide a systematic description of electrochemical reactions in which chirality has been induced using these three sources (Figure 1). Chemically modified chiral electrodes Electrochemical asymmetric reductions using chiral

• of a poly-ʟ-valine 6 coated graphite cathode for asymmetric electrochemical reductions in two consecutive reports. In the first communication, they carried out the asymmetric reduction of prochiral activated olefins 5 and 8, affording 7 and 9 with optical yields of 25% and 43%, respectively (Scheme 3

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• from both 3b and 1b. A (presumably two-electron) reduction peak was observed for 3a but only one return oxidation wave was observed. Upon repeated scanning the two one-electron reductions of 5a → 5a•− → 5a2− were observed, but still only a single (likely two-electron) return oxidation peak was observed

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• the reference NDI 1 and the cNDI 2 (due to the better solubility) were determined in comparison by cyclic voltammetry in CH2Cl2 and in the presence of 0.1 M n-Bu4PF6 as conducting salt (see Supporting Information File 1). The cyclic voltagram of NDI 1 shows two reversible reductions and one

• reductions of cNDI 2 to the radical anion 2•− were observed at E½(2/2•−) = −1.06 V and to the dianion 22− at E½(2•−/22−) = −1.50 V and show the electronic effect of the two n-propylamino substituents. Additionally, two reversible oxidations were observed at E½(2•+/2) = +0.99 V and E½(22+/2•+) = +1.40 V which

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• reductions with a NaBH4/ZnCl2 mixture or ʟ-Selectride®, respectively, to form aziridine alcohols (2S,1'R,1''R)-37 and (2S,1'S,1''R)-37. Reductive opening of the aziridine ring with concomitant removal of the chiral auxiliary produced protected (2S,3R)-35 and (2S,3S)-35 which were hydrolyzed to xestoaminol C

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• electrophilicity made lanthanides a catalyst of choice. Lanthanum complexes are widely used in synthetic chemistry for cycloadditions, reductions, benzimidazole syntheses, Biginelli reactions, hydrophosphinations of unsaturated substrates, double hydrophosphinylations of unactivated nitriles, Grignard additions, C

N-Arylphenothiazines as strong donors for photoredox catalysis – pushing the frontiers of nucleophilic addition of alcohols to alkenes

• Fabienne Speck,
• David Rombach and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 52–59, doi:10.3762/bjoc.15.5

• processes. Conclusion One of the major current challenges in photoredox catalysis is the design of chromophores suitable for the most reductive chemical reactions, like for instance reductions by alkaline metals, affording reaction conditions that are easier to handle. While solid sodium comes up with a

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• condensations of diethyl malonate on aldehydes, reductions of the resulting alkylidenemalonates, the preparation of the corresponding α-hydroxyimino esters and their final reduction. This synthetic pathway turned out to be general although some unexpected limitations were encountered. The synthetic

• ensuing reduction of 6u using sodium borohydride led to a somewhat better yield of compound 3u (as estimated by 1H NMR), side products resulting from over-reductions of the ester moieties were still observed. It is only when switching to tetramethylammonium borohydride that this was alleviated and the

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• conditions could be detrimental to the stability of some of these α-nitro acrylates. In the past, such reductions have been achieved under fairly uncommon conditions (NaBH4 in a mixture of isopropanol and chloroform over a large proportion of silica gel) [11][12]. However, when tried, no real overall

• 14. Syntheses of α-amino ester 18 and piperazinediones 23a,b. Syntheses of α-hydroximino ester 29 and α-amino ester 36. Synthesis of α-amino ester 43. Synthesis and reductions of α-nitro acrylates into α-amino esters. Supporting Information Supporting Information File 254: Experimental and copies of

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• in 91% yield. The ethyl ester was then smoothly reduced with DIBAL to the benzyl alcohol. While the in-process analysis (TLC and HPLC) indicated quantitative reduction, the isolated yields from the reductions were only poor to modest despite utilizing standard workup conditions with sodium potassium

Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• conditions reductions have mostly been limited to soluble reducing agents like DIBAL [7][8][9][10] and superhydride [11] which require special handling or expensive solid-supported borohydride species [12]. Recently, Seeberger and co-workers demonstrated a more cost-effective sodium borohydride-mediated flow

• (Table 1). Under these conditions, aldehyde reductions gave moderate to good yields (68–92%) which were comparable to those observed in batch in a significantly reduced reaction residence time (64 min vs 12 h). When expressed in terms of reactor space-time productivity (grams of product produced per

• ketones The striking difference in relative reactivity between the ketones and the aldehydes on the flow system allowed us to demonstrate selective reductions of aldehydes in the presence of various ketones by simple selection of an appropriate flow rate. This selectivity was shown by the reduction of

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• bond and consequently the reduction of the former should a priori occur preferentially [53][54][55]. According to the best of our knowledge, there are no literature reports concerning selective reductions of dibenzylic hydroxy groups in the presence of ortho-acetal or ortho-thioacetal functions. Such

• reductions may give an access to new series of ortho-formyl-protected diarylmethanes as well as their formyl-modified derivatives, obtained after deprotection of the 1,3-dithianyl group with one of the available methods [56]. Herein, we present the first example of a selective and efficient reduction of

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• arduous ion-exchange and drying processes required to render these materials soluble in organic solvents. Likewise, significant reductions in solvent processing (especially if these are high boiling and often toxic and/or carcinogenic) is an attractive green chemistry target. In this context, Thorwith et

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• to limited solubility of ammonia in THF. H2/Raney-nickel reductions are often carried out in alcoholic media where much higher concentrations of ammonia are achievable but would require a solvent exchange. There are many reports of continuous-flow chemistry methods for reductive amination of ketones

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• demonstrated by examples including the use of additional electrophiles (13a, 13b) or nucleophiles (9i, 9j), the use of a chiral auxiliary (15) or reductions of the obtained products 4 (16a, 16b). aCH2Cl2, 1 equiv Me2AlCl, rt; 13a: 1 h, 13b: 18 h. bdr was calculated from the 1H NMR results. Synthesis of diene

Conformational preferences of α-fluoroketones may influence their reactivity

• Graham Pattison

Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284

• atoms on the reactivity. The reactivity of α-fluoroacetophenone was compared to α-chloro- and α-bromoacetophenone in sodium borohydride reductions, using 0.2 equiv of NaBH4 to 1.0 equiv of α-fluoroacetophenone and 1.0 equiv of the second α-haloacetophenone to ensure the reaction stopped at low

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• reductions to arylamines were successful, an alternative approach was investigated in which the nitroarene group would be converted into the corresponding acetanilide 43. If this approach were successful, it was envisaged that the acetanilide 43 could be directly oxidised to carboxylic acid 44, thereby

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• , sultams have been prepared employing Diels–Alder reactions, radical cyclizations, reductions of sulfonylimines, ring-closing metatheses, nucleophilic aromatic substitutions and Heck cyclizations [14][15][16]. Earlier on, our group has developed versatile syntheses of sultams based on the transformation of