Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• achieved [31], Michael reactions with these nucleophiles have met with limited success [32][33][34][35][36][37][38][39]. In terms of enantioselective catalytic strategies, Kobayashi has reported the conjugate addition of azlactones to acrylates using a calcium pybox complex, but with enantioselectivities

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• electrophilic and nucleophilic α-functionalizations are possible, whereas with the use of α,β-unsaturated aldehydes the β-position is functionalized with nucleophiles and the γ-position with electrophiles. In this sense, Jørgensen and colleagues have developed the first organocatalytic asymmetric Michael

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

•  30). NFSI is a stable and non-hygroscopic crystalline solid with a mp of 114–116 °C. NFSI was shown to fluorinate a variety of nucleophiles. As seen in Scheme 31, trimethylsilyl enol ethers, enolate anions of ketones and esters, and aryl- and vinyllithiums were fluorinated with NFSI in moderate to

• F2/N2 system, but failed. Reagent 20-3 was synthesized using cesium fluoroxysulfate in 1991 (see section 1-15). Reagent 20-2 proved useful for the fluorination of both neutral and anionic nucleophiles under mild conditions. Scheme 45 illustrates some pertinent examples. Phenyl Grignard reagent

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• peptide, which can be further utilized as a Michael acceptor for a variety of nucleophiles. Based on their manganese-catalyzed allylation using Morita–Baylis–Hillman carbonates, the Ackermann group established an applicable late-stage C–H glycosylation of peptides (Scheme 12) [95]. Thus, allylative

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• chemistry; organocatalysis; phosphine; solvent-free synthesis; Introduction Phosphines are potent nucleophiles that are used as catalysts in many reactions, like Rauhut–Currier, Morita–Baylis–Hillman or Michael reactions [1][2][3]. The first step of these reactions is a conjugate addition of the phosphine

• alkoxide to yield the product iv and the phosphine. Our results disclosed in the following contribute to the rational selection of proper (pre-)catalysts for this and similar reactions also considering the oxygen sensitivity of the nucleophiles. Results and Discussion To compare the activity of the

• like structures were observed [24]. A more efficient transformation of acrylamide can be obtained with base catalysis. Using activated potassium carbonate, a reaction temperature of 40 °C, and 4 h reaction time give typically better conversions than those reported herein with nucleophiles [25]. Next

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• nucleophiles, along with transition-metal catalysis, in olefin alkylation reactions [18][19][20][21]. Apart from the early examples of olefin functionalization with transition metals, such as the well-known ethylene oxidation catalyzed by Pd(II) (the Wacker reaction) [23][24], the use of carbon nucleophiles in

• reported the use of active methylene compounds as suitable nucleophiles in intramolecular hydroalkylation reactions (Scheme 2) [25]. In the presence of PdCl2(CH3CN)2, the hydroalkylation of β-diketones 1 gave only 6-endo-trig cyclization products 2 in moderate to good yields (Scheme 2). The methodology

• nucleophiles beyond the usually employed dicarbonyl compounds to cyanoacetates, nitroacetates, fluoroacetates, lactones, lactams, and aromatic and heteroaromatic carbonyl compounds. The reactions were carried out at higher temperatures (120 °C) than used in the previous protocols involving more reactive

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• contain an adjacent electron withdrawing group (1, R1 = EWG) [13]. Installation of an electron withdrawing group adjacent to an isocyanide facilitates the deprotonation but creates weak nucleophiles 2 that are insufficiently nucleophilic to react with nitriles [14]. Described below is the use of Asmic

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• reaction conditions, we surveyed the scope and limitation of the cascade protocol. Initially, we explored the range of nucleophiles that were used to intercept the benzyl carbenium ion and the results are summarized in Scheme 6. All reactions with electron-rich aromatics containing a p- and/or o-methoxy

• reaction leading to the 4-allyl-substituted tetrahydronaphthalen-2-ol 14ai in 65% yield. On comparing the results from the anisole-type nucleophiles or thiophene with that from furans, it was observed that the reactions with furans furnished predominantly trans-14af and trans-14ag with a high degree of

• diastereoselectivity (cis/trans ratio = 1:99). The preferential formation of the trans-configured products for furan nucleophiles may be due to the fact that the addition of furan is reversible leading to equilibration to the more stable trans product. To test this hypothesis, we monitored the reaction by HPLC (Table

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• because of unfavorable steric interactions. To overcome this problem, reactive Michael donors must be used to achieve a good conversion in the reaction. In recent years, α-nitroketones have emerged as active nucleophiles in Michael reactions and a range of substrates have been explored [10]. Also, α

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• synthesis [1]. Electrophilic additions of alkynes give functionalized compounds, and cycloadditions such as the Huisgen reaction afford cyclic compounds. Weakly acidic terminal alkynes can be deprotonated, and the resulting acetylides are used as carbon nucleophiles. Terminal alkynes are also used for the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• ., benzaldehydes) and low-molecular-weight enolate nucleophiles, therefore, temperature regulation is vital for selectivity. This requirement for strict temperature control makes aldol reactions highly suited to flow processing conditions. In 2008, Tanaka et al. [96] disclosed several examples of aldol reaction in

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• -butanesulfinyl ketimine condensation (Scheme 2) [21]. Mechanism of addition of nucleophiles to N-sulfinyl imines The p-toluenesulfinamide 5 was first described by Davis and co-workers in a racemic form [22], and subsequently, the compound was prepared and isolated as a single enantiomer [23][24], becoming an

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• (phosphines, NHC-carbenes, bisoxazolines, pyridine-oxazolines, and miscellaneous) is used. Review Catalytic systems based on phosphine ligands A pioneering work on the enantioselective addition of boron-derived carbon nucleophiles to cyclic enones was published by the group of Miyaura et al. in 2005 [32

• ]. Specifically, they have dealt with the addition of potassium aryltrifluoroborates to conjugated cyclic enones differing in ring size [32]. The catalysts PdL1a,b exhibited great conversion and enantioselectivities (up to 99% and up to 96% ee) for various combinations of nucleophiles and enones (Table 1). The

• of the Pd-catalysed enantioselective addition of boronic acids to cyclic enones [37]. Addition of boron-derived C-nucleophiles to cyclic enones, catalysed by L2/Pd(TFA)2 [37]. Asymmetric addition of arylboronic acids to 2-cyclohexenone catalysed by L3/Pd(dba)2 [39]. Additions to different enones

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

• 3100–3400 cm−1 for the N–H bonds vibrations. NMR spectra record specific signals at 6.8–7.5 ppm for the shifts of the protons and 158–165 ppm for the 13C. Biguanides are good nucleophiles and easily carbonated under ambient conditions. They are stable over a wide range of pH. Often, heating in the

• corresponding bisamidinohydrazide product with a moderate 48% yield using the same conditions. Recently, the scope of the transformation was extended to other aminated nucleophiles such as hydroxylamine and methoxyamine. By using methoxyamine hydrochloride as a reactant along with 1 equivalent of pyridine, the

• N1,N5-substituted biguanides, that shows little variation in reactivity. By adapting these conditions, other reactants can be used such as nitrogen-containing heterocycles, other aminated nucleophiles, or ortho-substituted anilines, extending the scope of this reaction to a broader diversity of

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• -nucleophiles were compared under optimized reaction conditions (Table 3). In the case of 2-phenylethanol (2a) as an O-nucleophile, a similar reactivity, yield of mannoside 3a and α-selectivity were observed (Table 3, entries 1–3) among all the halides α-1a–c, although mannosyl chloride α-1b and bromide α-1c

• corresponding chloride α-1b or bromide α-1c. The stability of the latter in liquid SO2 at such a high temperature was unexpected due to their generally established labile nature. Additionally, when competitive glycosylation reactions in the presence of both O- and S-nucleophiles were performed, all mannosyl

• containing an excess of β-anomer β-16 was optimized to 60 °C, while for the more reactive α-anomer α-16 it was decreased to 30 °C. Regardless of the anomeric ratio, the desired O- and S-glucosides 18a–f were isolated in good yields. Besides, glycosylation of primary nucleophiles with benzyl-protected

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• nucleophiles. The second report, by Scheeren [7], working from a bis(phenoxy)chloromethane synthesis reported by Scheibler [8], described the conversion of phenyl orthoformate to bis(phenoxy)chloromethane with acetyl chloride and anhydrous hydrogen chloride, followed by reaction with potassium

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• deallylation of AllMSP is more efficient than its demethylation, which is surprising, because naturally DmdA catalyzes a methyl-group transfer. This finding may reflect the high reactivity of the allyl group towards nucleophiles. Other compounds originating from AllMSP included the di- and trisulfides 2, 26

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

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• secondary amines as the nucleophiles [49]. In their protocol, the regioselectivity is controlled by PyBroP catalyst, which acts as the N-oxide activator. Manley and Bilodeau reported the amidation of heterocyclic N-oxides at the C2-position using oxalyl chloride for activating the N-oxides [50]. In addition

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• phosphonodepsipeptides 56 and 57, respectively. The oxidative activation was carried out in the presence of alcohols as nucleophiles so that stoichiometric formation of the phosphonochloridate was avoided and side reactions were minimized (Scheme 9) [25]. The current chlorination is a mild and neutral method for the

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• . A series of substituted products was obtained in SNAr reactions between 2,6-bistriazolylpurine derivatives and O- and C-nucleophiles under mild conditions. The products were isolated in yields up to 87%. The developed C–O and C–C bond forming reactions clearly show the ability of the 1,2,3-triazolyl

• -nucleophiles [12][13][14] and in metal catalyzed reactions of halopurine derivatives [15][16][17][18][19][20]. Modifications of purines with O-nucleophiles are based on SNAr reactions between 6-halopurine derivatives and alcohols [21][22][23][24][25][26][27][28] in the presence of a base. Alcohols are used in

• ][45][46][47][48][49][50]. In the case of C-nucleophiles there are a few precedents of transition-metal-free substitution of chloro [51][52][53][54][55] or 1,2,4-triazolyl [56] moieties as leaving groups at the C6 position of purine. These transformations usually require prolonged time and elevated

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

• < T < −40 °C in the presence of aromatic nucleophiles, thiophenes 72-Cl and 72-Br could be converted into 74-Cl and 74-Br derivatives via a side-chain arylation reaction. When the reaction was conducted at −40 °C, the reactivity was shown to be governed by the nature of the halogen atom. For the

• tetralin derivatives 144a and 144b, respectively (Scheme 36). In addition, 144a could be further converted into 146 in the presence of aromatic nucleophiles (e.g., benzene or toluene). Similarly, derivatives 147a–c could also be converted into indanol derivatives 148a–c in high yields (Scheme 36) [95]. Ma

• exploited the reactivity of the trifluoromethylated iminium ion 192 and extended the scope of the reaction to a larger panel of nucleophiles, including alcohols, amines, aromatic and vinyl derivatives, as well as silylated nucleophiles (Scheme 47) [122]. Brigaud and Huguenot also suggested the formation of

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

• isomerization [36]. Several nitrogen nucleophiles have been evaluated as catalysts to promote the difluorocarbene formation from TFDA in order to bring about the cyclopropanation of a 2-siloxybuta-1,3-diene derivative; 1,8-bis(dimethylamino)naphthalene (proton sponge) was found to be particularly effective [37

• opposite to the CF2 fragment and the formation of a 2,2-difluorohomoallyl cation. Cleavage of the distal bond. Ring opening of gem-difluorocyclopropyl ketones: The gem-difluorocyclopropyl ketones such as 106 and 108 underwent nucleophilic ring-opening reactions induced by thiolate nucleophiles. A distal

• (Scheme 65) [97][98]. This contrasts with the previously discussed (Scheme 49) distal bond cleavage of ketone 106 in reactions with thiolate nucleophiles. It is likely that an elimination of HF from 106 to form a monofluorocyclopropene intermediate took place under the more strongly basic conditions. This

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• olefins [13][14]. Aziridines are otherwise accessible from a variety of acyclic precursors [15][16][17], even stereoselectively [18][19][20], and through derivatization of 2H-azirines. The reactions using 2H-azirines as electrophiles proceed with several nitrogen, oxygen and sulfur nucleophiles, enabling

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• leaving group in SNAr reactions with S- and N-nucleophiles [19][20][21]. It is worth to note that 2/6-amino-6/2-triazolylpurines possess high levels of fluorescence [19][22][23][24]. Herein, we describe an extension for SNAr reactions that makes use of the 1,2,3-triazole leaving group of 2,6

• analysis. This is similar to the previously observed substitution pattern in SNAr reactions of 2,6-bistriazolylpurine derivatives with simple N- and S-nucleophiles. Experimental General information Commercially available reagents were used as received. The reactions and the purity of the synthesized