An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• malononitrile under catalyst-free conditions have been reported [29]. Wang et al. reported the functionalization of benzylic C–H bonds of 2-methylazaarenes by nucleophilic addition to aromatic aldehydes catalyzed by acetic acid using harmful chlorinated solvent, and this reaction suffers from longer reaction

• mmol of 1a will inter react to another 1 mmol of 1a) and this inter reaction influences the nitrogen atom present in the compound to act as a Brønsted base. This resulting Brønsted base accepts benzylic C–H protons to furnish the respective enamine A, which facilitates the further nucleophilic addition

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

• between carboxylic acid/alcohol 76 and enal 77 (Scheme 10a) [46]. Analogously to the mechanism outlined in Scheme 9, it was proposed that formation of excited state iminium ion 66* is used to oxidise 76 to give radical cation 76•+ and alkyl radical 66•. Nucleophilic addition from the carboxylic acid or

• al. [94] it is suggested that this reaction uses 1O2 for the oxidation, and proceeds through transition state 219‡ for the hydrogen-bonded catalysed nucleophilic addition step. Jiang et al. recently applied a similar dual catalytic system to the dehalogenative protonation of α,α-chlorofluoro ketones

• intermediate 239•, which abstracts a hydrogen atom from TRIP-thiol to produce enantioenriched cyclic sulfonamides 239 in excellent yields and enantioselectivities (28 examples, up to 98:2 er). Chiral phosphates have also been used to catalyse the enantioselective nucleophilic addition of indoles 241 to imines

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

• sensory material for selective recognition of cesium cations in water. In another event, Hirao’s group has prepared trioxosumanene 40 in the presence of RuCl3 and t-BuO2H which could be used as a key building block to generate diverse significant electroactive materials by virtue of nucleophilic addition

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• the Henry reaction, the nitroethane anion intermediate, coordinates to the Ni-porphyrin, which slows down nucleophilic addition to the nitrobenzaldehyde. Hence, the switchable catalyst 1 contains both, a catalytic center (nitrogen lone pair) and an inhibitor (Ni2+ ion). If the nitrogen lone pair

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• radical adds to the central carbon of the allene giving a conjugated N-acyliminium that undergoes nucleophilic addition by arylamines and alcohols. Keywords: allenamide; allene; intermolecular; N-acyliminium; photoredox; Introduction Allenamides (Scheme 1, 1) and their congeners have attracted

• conjugated N-acyliminium 14. The iminium 14 could then undergo traditional nucleophilic addition giving the addition product. Given that the iridium complex Ir[(ppy)2(dtbbpy)]PF6 had been effective [47][48][50] in this radical/cationic pathway with enamides we would now like to report our preliminary

• nucleophilic addition at the α-position giving the observed N,N’-allylaminal product 43. Conversely, addition of a nucleophile at the γ-position of E-42 gives the observed Z-enamide 44; and addition at the γ-position of Z-42’ gives the same observed Z-enamide 44 after C–N bond rotation. Conclusion In

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• nucleophilic addition, the authors suggested the tentative mechanism depicted in Scheme 34. As shown, γ-fluoride loss from enolate I, formed after the conjugate Michael addition, would lead to the formation of difluoroenone II. This could in turn undergo a nucleophilic addition of water, followed by a retro

• PKR of chiral N-tethered 1,7-enyne bearing a vinyl fluoride [64]. Catalytic intramolecular PKR of chiral N-tethered 1,7-enynes [64]. Model fluorinated alkynes used by Riera and Fustero [70]. PKR with norbornadiene and fluorinated alkynes 58 [71]. Nucleophilic addition/detrifluoromethylation and retro

• Diels-Alder reactions [70]. Tentative mechanism for the nucleophilic addition/retro-aldol reaction sequence. Catalytic PKR with norbornadiene [70]. Scope of the PKR of trifluoromethylalkynes with norbornadiene [72]. DBU-mediated detrifluoromethylation [72]. A simple route to enone 67, a common

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• nucleophilic addition of another molecule 2 takes place to furnish the tricomponent adduct 4, which undergoes elimination of ammonia to afford the corresponding ring-closed intermediate 7 [37]. The latter undergoes a proton-transfer process to form intermediate 10 [38]. Thereafter, the subsequent step involves

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• thiiranes was used for the synthesis of thietanes. Isocyanoalkanes 415 can be considered as nucleophiles. However, after the nucleophilic addition, they could become electrophiles. Thus, they can be applied in the nucleophilic ring expansion of thiiranes 416, in which the generated thiolates 417 as

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

• an N-acyl-4-methoxypyridinium salt using a copper/phosphoramidite catalytic system (Scheme 3) [20][21]. The authors highlighted that the N-acylpyridinium salts were unstable species and that their instability affected the regioselectivity of the dearomatisation process upon the nucleophilic addition

• asymmetric additions to N-heteroaromatic alkenyl compounds are less developed. This deficiency is largely due to the intrinsically low reactivity of alkenyl-substituted heterocycles towards nucleophilic addition compared to common Michael acceptors. A way to lift this barrier was introduced in 2016 by

• alkenylpyridines in the substrate scope. The reason for this was the markedly lower reactivity of alkenylpyridines towards nucleophilic addition as compared to other alkenylheteroarenes. For the same reason, the synthesis of chiral pyridine derivatives has always been considered a challenge in organic chemistry

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• formation of the corresponding hydroxy-substituted derivative 5, resulting from the nucleophilic addition at the carbon atom C2’ (Scheme S3, Supporting Information File 1). This was clearly evidenced by the characteristic 1H NMR signals [74][77] at δH = 6.69 (d, 7’-H), 3.23 (s, NMe), 1.48 (s, 3’-Me), and

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• (Scheme 27b). The sulfate radical then reacted with formamide (106) to produce the carbamoyl radical 125, which could perform a nucleophilic addition to the C-2 position of the protonated benzothiazole 126. A deprotonation, followed by an oxidation, most probably by the intermediates 121 and 122, could

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• ) and Cu(II)@IPSi (1b) was investigated in the one-pot three-component condensation of various benzyl bromides, various phenylacetylenes, and sodium azide (Scheme 1). The authors stated that benzyl azide was formed in situ by the nucleophilic addition of the benzyl bromide and sodium azide. Subsequently

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• the generation of sodium 1,3-thiaselenol-2-ylmethylselenolate from 1,3-thiaselenol-2-ylmethyl selenocyanate or bis(1,3-thiaselenol-2-ylmethyl) diselenide followed by nucleophilic substitution reactions. Sodium 1,3-thiaselenol-2-ylmethylselenolate underwent nucleophilic addition to alkyl propiolates in

• -thiaselenole; nucleophilic addition; nucleophilic substitution; rearrangement; seleniranium intermediate; Introduction The regio- and stereoselective synthesis of organoselenium compounds based on selenium-centered electrophilic reagents has been one of the most important and effective directions in

• -ylmethylselanyl heterocycles connected by a carbon bridge was demonstrated (e.g., compound 6k containing two 1,3-thiaselenol-2-ylmethylselanyl heterocycles connected by a six-carbon bridge). The 1,3-thiaselenol-2-ylmethylselenolate anion generated from selenocyanate 4 was also subjected to a nucleophilic addition

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

• anion Int1 by hydride addition to the terminal carbon atom of the isocyanide group in 2a via transition state TS1. This anion undergoes nucleophilic addition to the thiocarbonyl moiety of the xanthate 1a to generate the intermediate Int2 via transition state TS2. In the next step, elimination of the

• could subsequently undergo a nucleophilic addition to the thiocarbonyl group via a transition state, which was analogous to TS2 depicted in Scheme 2 above. However, in this step, instead of the nitrogen anion, the carbanion was the nucleophile. Subsequently, elimination of the thiomethyl or thiolate

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

• electrooxidation in the aqueous phase. The [Br+] thus generated oxidizes the N-oxyl/N-hydroxy species, leading to the formation of the N-oxoammonium species in CH2Cl2. The nucleophilic addition of racemic 63 to this N-oxoammonium species might further generate 65 and a steric hindered environment would favor the

• ). As per the proposed mechanism, products 122 were obtained via nucleophilic addition of enamine 124' to electrophilic intermediate 127 (generated from the anodic oxidation of 120) followed by sequential hydrolysis, proton transfer and immediate intramolecular condensation (Scheme 41). Very recently

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• is provided in Scheme 5 [21][31][32]. Initial activation of ynamide 4a by silver catalyst can afford the Ag complex A, which can isomerize to the keteniminium ion intermediate B. A nucleophilic addition of 5-aminoisoxazole 8a to silver species B leads to the formation of alkenylsilver species C

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• their isolation and structural characterization are still less common. A very convenient access to such betaines is provided by the nucleophilic addition of tertiary phosphanes to electron-deficient alkenes, alkynes and allenes (phospha-Michael addition), which generates the betaines as reactive

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

• -2-carbaldehyde on the other hand resulted in appreciable yields under similar reaction conditions. The authors have successfully constructed a big library of 28 compounds with varying structure. In 2013, Gao et al. have exploited the TM-catalyzed nucleophilic addition reactions of haloalkynes 5

• single-electron transfer (SET) with CuI followed by hydride abstraction/intramolecular nucleophilic addition and loss of a proton forming the desired compound 49 (Scheme 19). Cu(I)-catalyzed intramolecular oxidative C–H amidation of N-pyridylenaminones 61 for the synthesis of imidazo[1,2-a]pyridine

• towards differently substituted reacting compounds. Acetophenones bearing EWGs reacted faster than those with EDGs as these groups might be unfavorable for the nucleophilic addition step during the reaction (Figure 3). The advantageous point of the protocol involves the recovery and reusability of the

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• elemental sulfur and NaH generates a polysulfide anion that is able to attack the carbenoid carbon atom of isocyanide 1a yielding the isothiocyanate intermediate 8. Then, the present nucleophile (NuH, alcohol or thiol) undergoes a nucleophilic addition on 8 providing thiocarbamate 3a. Conclusion In summary

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• hexamethylenedisalazane is necessary. However, in this approach, the nucleophilic addition on the nitrile group and the cyclization was achieved without the addition of a catalyst [44]. This reaction possesses a highly atom economical character and requires only triethylamine (40 mol %) as a base in EtOH and provides

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• component that leads to the formation of an imine intermediate A. The formed Schiff base is in equilibrium with its iminium cation B as a result of an intramolecular proton exchange with the carboxylic acid moiety which activates the iminium ion for the nucleophilic addition of isocyanide. Consequently, the

• electrophilic centre of the iminium ion in B is subjected to a nucleophilic attack of the isocyanide to furnish the intermediate C. Then, a second nucleophilic addition takes place at this nitrilium intermediate C with an intramolecular nucleophilic addition of the carboxylate anion. The final step is an acyl

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• formation of the gem-dichloro-α-lactam intermediate 17f which would undergo ring opening by nucleophilic addition of pyrrolidine followed by hydrolysis of the resulting α,α-dichloro-α-aminoacetamide 18f (Scheme 12). To access aminocyclopropanes, the hydrogenation of (arylmethylene)cyclopropane 13f was

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• nucleophilic addition of bis(trimethylsilyl)ketene acetals to pyrazines activated with methyl chloroformate was found to afford polycyclic γ-lactones in moderate yields [3][10][11]. The work by Garduño-Alva and co-workers demonstrated that these TMS-ketene acetals can be regioselectively added to substituted N

• the nucleophilic addition of Grignard reagents to N-acylpyrazinium salts. A literature search showed this organometallic reagent reacting with pyrazine N-oxides towards the one-pot synthesis of N-Boc-protected N-hydroxy-substituted piperazines in good yields [6]. Methylmagnesium iodide was observed

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

• broaden the substrate scope for the nucleophilic addition of methanol to styrenes through photoredox catalysis. These N-phenylphenothiazines differ by their electron-donating and electron-withdrawing substituents at the phenyl group, covering both, σ and π-type groups, in order to modulate their

• (without considering the solvent term) [29] we estimated the excited state potential of these catalysts to be as low as Ered(X+·/X*) ≈ −2.9 to −3.0 V (vs SCE). The proposed photoredox catalytic mechanism (Figure 4) for the nucleophilic addition of methanol to olefins starts with photoinduced electron

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• second step, target product 5a was not observed, and compound 22 was isolated in trace amounts. Its formation may be explained by an initial nucleophilic addition of water to intermediate chromene 3, oxidation to keto-derivative and condensation with nitromethane (Scheme 6, reaction 2, IV). Conclusion In