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

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• notable in showing that the intermediate ester enolate 14 possessed sufficient stability not to undergo significant β-elimination under conditions of its generation and its alkylation: slow addition of pre-cooled LDA (−70 °C) to a mixture of the acetonide and electrophile in THF/HMPA at −78 °C, followed

• by slow warming to ≈−10 °C before work-up. Finally, the reaction displayed remarkable stereoselectivity, in that the electrophile was introduced on ostensibly the more hindered face of the enolate (that is, cis (“contrasteric”) [24] to the unenolised ester group). The former observation was

• pseudoaxial methyl of the gem-dimethyl group [18][24]; it was proposed that the axial methyl group directed electrophile incorporation away from itself (Scheme 4). The fragile nature of the lithium ester enolate of dimethyl tartrate acetonide (to β-elimination with loss of acetone) was evident from Seebach’s

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• success of this bis-nucleophile/bis-electrophile [3 + 2] annulation is its well-defined step chronology in combination with the total chemoselectivity of the former step. This [3 + 2] C–C/O–C bond forming annulation protocol could be also extended to 1,3,5-triketones as well as 1,3-bis-sulfonylpropan-2

• , resonance-stabilized acetamides and cyclic α,β-unsaturated-γ-oxicarbonyl derivatives are used as bis-nucleophile and bis-electrophile partners, respectively. This process involves an intermolecular Pd(0)-catalyzed C-allylation (Tsuji–Trost reaction)/intramolecular nitrogen 1,4-addition sequence (Scheme 1

• , top reaction). The success of this bis-nucleophile/bis-electrophile [3 + 2] C–C/N–C bond-forming annulation is due to the well-defined chronology of the steps and the total chemoselectivity of the initial step (C-allylation). Another non-trivial feature of this process is that the possible undesired

SO₂F₂-mediated transformation of 2'-hydroxyacetophenones to benzo-oxetes

• Revathi Lekkala,
• Ravindar Lekkala,
• Balakrishna Moku,
• K. P. Rakesh and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 976–980, doi:10.3762/bjoc.15.95

• fumigant for more than five decades [25][26], and only recently it has attracted significant attention as an organic synthetic reagent. SO2F2 is a cheap and relatively stable gas (up to 400 °C when dry) and a highly reactive electrophile [27][28][29]. Under basic conditions, SO2F2 hydrolyzes rapidly into

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• potential. Given the issues encountered in employing MTB, we next investigated the introduction of the phosphonate ester as the nucleophile rather than as the electrophile (Figure 2). Commercially available alcohol 10 was prepared by adapting a previously reported literature procedure where diethyl

• electrophile in 14 means that the critical alkylation step is conducted at room temperature. Additionally, the preparation of chloride 19 is a solventless reaction and the subsequent conversion of 19 to iodide 14 takes place in acetone, a green solvent. Our route also produces fewer byproducts and is higher

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• (2R,4S)-anti isomer [35][36]. As the configuration at C4 was expected to be invertible in a later step, we aimed for the (2R,4R) configuration by choosing (R)-propylene oxide as electrophile. We obtained an acceptable ratio of diastereomers of 11 (84:16 in favour of (2R,4R), 62% combined) after having

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• ; sulfoxide; thiol-free; Introduction Throughout the years, several strategies have been developed to build up organic compounds bearing a sulfide moiety [1][2]. Often, thiols (or the corresponding thiolate anions) are employed as nucleophilic sulfur reagents in order to react with a suitable electrophile [3

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• . TIPS: triisopropylsilane. TBDMS: tert-butyldimethylsilane). Hydrogen-bond-catalyzed nucleophilic substitution of 18 with BIFOXSi(OH)2 (9) and nucleophile silyl ketene acetals 11. 18 and 9 form an activated electrophile ion pair complex which yields C–C coupling product 19 (Table 10). Nucleophilic

• substitution of 20 with BIFOXSi(OH)2 (9) and nucleophile silyl ketene acetals 11, 20 and 9 form an activated electrophile ion pair complex which yields C–C coupling product 22 (Table 11). Hydrolysis of BIFOXSiCl2 (7) to BIFOXSi(OH)2 (9) (Scheme 3) in different solvent mixtures, with or without KOH at different

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• formation of 1. Thus, the slow addition of 13 to a well-stirred solution of methyllithium (MeLi, 2 equiv) liberated gaseous CH4 (1 equiv) so that 13 was completely consumed before the electrophile t-BuCH=O (4; 4 equiv) was introduced and furnished adduct 7 but no trace of 1. The worst case (with 1 as a

• , metal cation assistance was not necessary for the rapid carbanion release from the α-silyl compound 24 in the presence of Bu4N+F− in catalytic amounts. (ii) Most of the above alkoxide fission reactions were conducted in the presence of an electrophile for trapping the released nucleofugal carbanion

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• situ (Scheme 4). This transient species is a powerful internal electrophile which would readily undergo intramolecular attack even by poor nucleophiles like the deactivated arylamino groups present in compounds 3. Conclusion Our synthetic approach represents the first method for the preparation of 2

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• efficiency. These results strongly suggest that 2-Zn can be successfully employed for the coupling reaction with an electrophile bearing a reactive functional group. Lastly, this synthetic protocol could be applied to prepare the CF2CF2-substituted heteroaromatic compound 4r from 3-iodopyridine (3r

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• hydroarylation of glyoxylate with pyrimidine containing indoles and pyrroles 7 to provide products 63 with high productivity (Scheme 40) [79]. Similar to the imine, isocyanate is also an efficient electrophile for hydroarylation of C=N bond. It provides a high atom- and step-economical method for the preparation

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• , contains a masked α,β-unsaturated 1,4-dialdehyde moiety, the presence of which has been proposed to be the cause of the feeding deterrent activity exhibited by the mollusc. We have found onchidal acts as an electrophile, reacting rapidly with the model nucleophile n-pentylamine forming diastereomeric

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• strong base (NaH). Further exploration of the reaction conditions towards the functionalized macrocycles 18 and 19 indicated that the reaction proceeds best at 0 °C, using NaH as a base combined with a large excess of the appropriate electrophile 17 (15 equivalents per hydroxy moiety, Scheme 6

• avoiding chromatography. The unfunctionalized macrocycles are labile in neutral solution or basic medium. However, post-functionalization of the macrocycles was successfully realized at low temperatures and with a large excess of the electrophile. Functionalization of the [2 + 2] macrocycle 6 towards an

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• group report are scaffolds and moieties seen in typical medicinal chemistry syntheses. There are numerous examples of amino acid-derived substrates, either as the methoxybenzene electrophile (tyrosine type derivatives) or as the nucleophile (histidine and related structures such as the depicted triazole

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• occupying the equatorial positions, and the electronegative ligands are in the apical positions (Figure 1, 1 and 2) [8]. Hypervalent iodine(III) reagents are electrophile in nature, resulting from the node in a hypervalent nonbonding orbital, a 3-center-4-electron (3c-4e) bond (L–I–L), which is formed by

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• . PIFA (31) is a more electrophilic iodine(III) reagent than PIDA (15) due to the presence of two trifluoroacetoxy groups. There are some approaches for the synthesis of spirocyclic compounds where PIFA (31) is used as electrophile. Recently, Lewis and co-workers [73] reported the conversion of arnottin

• synthesis In 2005, Wipf and Spencer [79] reported the first total synthesis of the Stemona alkaloid (−)-tuberostemonine (40). In this report, PIDA (15) was used as an electrophile for the synthesis of spirolactone 16 in 35% yield by the cyclization of L-tyrosine 14 in nitromethane at room temperature for

• of tyrosine derivatives to spirolactams using iodine(III) reagents. In this reaction, oxazoline derivatives 41 were cyclized to spirocyclic products 42 using PIDA (15) as an electrophile in trifluoroethanol at room temperature for 30 minutes. The desired products 42 were isolated in moderate yields

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• –ring closure reaction of alkynyl substrates with diaryliodonium salts can be depicted as follows: first the Cu(III)–aryl electrophile forms an intermediate with the triple bond of the reactant, then the aryl moiety migrates to the activated triple bond which is followed by a fast ring-closing step. The

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• a carbon–carbon bond-forming reaction occurring between the α-position of an activated alkene and a carbon electrophile such as an aldehyde. Employing a nucleophilic organocatalyst [26], such as a tertiary amine or a phosphine, this simple reaction provides densely functionalized products, such as α

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98