Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• an electrophile, the crude product 2a was treated with butyllithium, followed by the reaction with carbon dioxide to afford pyrrole carboxylic acid 6 in a good overall yield (Scheme 5). The trifluoromethyl group on the nitrogen was not affected by these highly basic reaction conditions. The mechanism

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

• simultaneous activation of both the nucleophile and the electrophile [12][13][14][15]. Quinine derived sulfonamides were first introduced to the literature by Song et al. [16]. Since then, many contributions were made regarding their applications in a variety of reaction types [17][18][19][20]. However, sulfa

• Houk’s mode of activation was of lower energy than Wynberg’s activation mode, in which the activation and orientation of the nucleophile is done by the quinuclidine core [43]. According to our proposed model, the protonated quinuclidinium ion stabilizes the newly forming alkoxide on the electrophile

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• nucleophilic esterification of potassium 1-(N-benzyloxycarbonylamino)alkylphosphonates 172 with alkyl halides in the presence of 18-crown-6. They also prepared a phosphonodepsidipeptide 174 with ethyl chloroacetate (173) as an electrophile (Scheme 33) [53]. The macrocyclic peptidyl phosphonodepsipeptide 180

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• nitrogen with a suitable electrophile, the use of a strong base (e.g., NaH) in combination with the chemical waste being generated (from the leaving group), and potentially unfavorable polar aprotic solvents (DMF, NMP) prompted consideration of a more atom-economical approach. The follow-on work focused on

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• pyridine as a scavenger for the liberated HCl, gave solutions of crude diacylated product 18 in acceptable purity after simple filtration as work-up. It was reasoned that the activation of the electron-rich pyrrole (with generic electrophile X2 as shown) would hasten cleavage of the ester and that

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

• intermediate allylic cation which was the electrophile in a Friedel–Crafts reaction with 159. The subsequent desilylation of the Friedel–Crafts product gave an α-fluorinated ketone intermediate which then reacted with a second equivalent of 159 in a (Z)-stereoselective, chelation-controlled process. Fu et al

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• sulfides by the acetamidosulfenylation of alkenes [12], among others [13][14][15]. Sulfur-containing compounds are important intermediates in organic synthesis, being able to act as an electrophile or nucleophile in many organic transformations [16][17][18]. Still, many of them are pharmacologically active

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• of an alkyl electrophile has been reported to date [35]. This process used an umpolung strategy with activation of typically electrophilic perfluoroalkylsulfenamide reagents by iodide, releasing −SC2F5 or −SC3F7 anions in situ, which could then react with a selection of alkyl halides (Scheme 1b). In

• synthesis of BT-SCF3 from inexpensive 2-mercaptobenzothiazole (MBT) can be readily adapted to provide a wide range of different BT-SRF reagents. Moreover, in situ activation of the benzothiazolium salt by the alcohol provides a highly reactive alkyl electrophile, which can compensate for the inherently low

• substitution reactions of this type are synthetically appealing as they avoid pre-generation of an active electrophile such as an alkyl halide. A selection of benzylic alcohols 2 was reacted under the standard conditions with BT-SC2F5 (1.25 equiv) and NEt(iPr)2 (2 equiv) in MeCN at −40 °C, providing the

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

• starting materials, rather expensive catalysts, harsh reaction conditions or low product yields. Transition-metal-catalyzed, electrophile-induced and oxidative radical cyclizations of ortho-alkynylated biaryls are widely used for the synthesis of polynuclear aromatics [57][58][59][60][61][62][63][64][65

• steps of the method are electrophile-induced 6-endo-dig cyclizations of ortho-alkynylated biaryls. The overall yields of helicenes in five stages of the synthesis exceed 30%. The single-crystal X-ray diffraction analysis revealed the non-planar crystal structures of the synthesized helicenes responsible

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• 1a and TBAI, leading to an excess of the CF3Se− species, no significant improvement was observed (Table 1, entry 8). On contrary, the use of 2 equivalents of the electrophile 2a, to ameliorate the CF3Se− anion trapping, had a significant effect and gave a very good yield of the product (Table 1

• ). Consequently, the nucleophilic substitution is in competition with this relatively fast oxidation. By adding an excess of the electrophile 2, the substitution is favored detrimentally to the oxidation. Nevertheless, with weaker or hindered electrophiles, the oxidation reaction is favored compared to the slower

• concerning the direct nucleophilic trifluoromethylselenolation. The nucleophilic fluoroalkylselenolation of alkyl bromides. Yields were determined by 19F NMR spectroscopy with PhOCF3 as an internal standard and yields of isolated products are shown in parentheses. aWith 1 equiv of electrophile 2. bStarting

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• , and 18b. The corresponding imidazo[1,5-a]pyridines 16g, 19ag, and 18bg were obtained in a highly efficient manner (Scheme 6). In addition, α-nitroacetic ester (1i) was probed as an electrophile in the reaction with substrate 12 in order to demonstrate that the phosphorylated nitronate function is a

• superior electrophile in comparison to the ester function. Indeed, this bielectrophilic reagent reacted only at the nitro group, providing the amide 20 as the sole product. The yield was quite marginal, primarily due to decomposition of the fragile ester functionality under the harsh reaction conditions

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

Efficient [(NHC)Au(NTf₂)]-catalyzed hydrohydrazidation of terminal and internal alkynes

• Maximillian Heidrich and
• Herbert Plenio

Beilstein J. Org. Chem. 2020, 16, 2080–2086, doi:10.3762/bjoc.16.175

• ] leads to the activation of the triple bond for a nucleophilic attack, generating a vinylgold complex [39][40]. This is followed by the substitution of LAu+ with an electrophile E, corresponding (for E = H+) to a protodeauration and is leading to the release of the desired organic product [41]. The

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• with the reactive (trifluoromethyl)iminium group as the electrophile (Scheme 2). The thermal conversion of 4-Ch into 7 was optimized and finally allowed the preparation of the latter from 1a in a one-pot, two-step, temperature-dependent Diels–Alder reaction/intramolecular SE(Ar) reaction sequence in

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

• center. This in turn led to their increased nucleophilicity as compared to the standard Ugi adducts. As such, the stereocenter at the peptidyl position could be installed and stereodefined through the reaction with a suitable electrophile. Towards this end, we were able to deploy an asymmetric cinchona

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

• catalysis involving two catalysts and two catalytic cycles acting in a cooperative way to create a new bond, turned out to be a powerful strategy. According to a simplified representation, synergistic catalysis involves the concurrent activation of a nucleophile and an electrophile by means of two distinct

• , if both the nucleophile and the electrophile are activated independently by distinct functional groups on the same catalyst, this is referred to as bifunctional catalysis (Figure 2, (1)) [48]. When the two catalysts work in a cooperative way to activate only one substrate, this is classified as

• )) [51][52]. Finally, the panel of these multicatalyzed reactions is complemented with the above-mentioned synergistic catalysis strategy, i.e., the simultaneous activation of an electrophile and a nucleophile by two distinct catalysts in order to achieve a single chemical transformation (Figure 2, (4

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

• , the ability of transition metal complexes to intercept alkyl radicals has been exploited for expanding the possibility of C–C bond formation reactions to cross-couplings. In all of these transformations, the substituents on the alkyl radical determine if it reacts as a nucleophile or an electrophile

• for the synthesis of the arylated heteroarenes 12.3 via an intermolecular process [79]. Alemán and co-workers used PHTH (OD16) for the synthesis of various heteroatom-containing bicycles 12.4 through a tethered electrophile approach [80]. For the second strategy, König and co-workers developed an

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

• (1Δg) the main photoactive species in solution [63][64][65]. Singlet oxygen is a highly reactive electrophile toward electron-rich organic molecules/atoms such as alkenes, dienes, and heteroatoms (N, P, S, Se, etc.) making this molecule very effective in pericyclic reactions and heteroatom oxidations

• -α-hydroxy-β-keto esters in 81–93% yields and 39–75% ee (Scheme 41). The mechanism of this reaction involves the attack of the enolate paired with the chiral counter ion PTC to the singlet oxygen electrophile to give the hydroperoxide intermediate, which is converted to α-hydroxy-β-keto esters

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ). This species serves as an active catalyst, nucleophilic at boron, via coordination with an alkene (307) which undergoes insertion to deliver the B–C bonded species via an intermediate that either undergoes elimination or reacts with an electrophile to form the product (e.g., 308, 309, Scheme 49) [92

• . This step is then followed by treatment of the reaction intermediate with an electrophile to deliver the desired borylated compound [98]. An efficient Cu-catalyzed (via in situ formed [(R)-DTBM-Segphos]CuH) protocol for an asymmetric net hydroboration of internal alkenes 343 with high regio- and

• cleavage of the B–B bond in B2pin2 to form the borylcopper intermediate. Following this, the metallo-enamine is formed before reacting with an electrophile [130]. A method to prepare β-trifluoroborate salts 423–427 each containing a carbonyl group was developed using a combination of CuCl/CyJohnPhos/NaO-t

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• electrophile [8][10][11]. This paper describes in full detail the racemic system using allylic carbonates. The allylic cross-coupling of aromatic aldehydes and allylic carbonates with a silylboronate by the merging of a copper–N-heterocyclic carbene catalyst and a palladium–bisphosphine catalyst produced

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• carbon atom can act as either a nucleophile or an electrophile. To account for the reactions reported herein, the isocyanide carbon atom acted as an electrophile in the reaction with a hydride (or a dimethylamide anion stemming from DMF). A facile general protocol was described for the unexpected

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• pursue molecular modeling experiments to determine the atomic partial charges and condensed-to-atom Fukui functions [37]. The former parameter can be used as an estimation of the reactivity: a higher net charge is related to a more facile reaction with a hard electrophile [38]. On the other hand, Fukui

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• ][8]. Every student of organic chemistry is taught the importance of arenium ions in the classic two step SEAr mechanism for electrophilic aromatic substitution. Addition of an electrophile to an arene leads to a bound species, sometimes called a σ-complex, which then loses a proton at the site of

• substitution to yield the product [9]. Of course challenges to this simple mechanism exist [10][11][12][13][14][15], including the recent proposal of a one-step process [16]. Reaction dynamics of electrophile–arene π complexes may also play a role in site selectivity [17]. It is less commonly known that

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• source and behaves as a nucleophile. The electrophile, such as an alkyl chain or an aryl ring with halides or sulfonates, reacts with the fluoride source (Scheme 1a). On the other hand, in the electrophilic fluorination, the nucleophile may be a carbon anion (e.g., Grignard reagent), a compound with

• electron-rich unsaturated bonds (arene, alkene, or alkyne), or a substrate having a nucleophilic and labile bond (e.g., C−Si, C−Sn, and C−B), while the electrophile is the fluorination reagent (Scheme 1b). As shown in Scheme 1d, many nucleophilic and electrophilic fluorination reagents have been developed

•  17). More recently, Yamamoto and co-workers [56] described a palladium-catalyzed general method for aromatic C–H fluorination with mild electrophilic fluorinating reagents at room temperature (Scheme 18). Notably, in this process, a reactive transition metal fluoride electrophile B is catalytically