Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• alcohols promoted by trimethylsilyl polyphosphate (PPSE) in solvent-free conditions allowed for the synthesis of several hitherto unreported seven-membered iminothioethers bearing 2-aryl, alkenyl, aralkyl and alkyl substituents. The cyclodehydration reaction is likely to involve an SN2-type displacement

• alcohols. In both cases, PPSE would activate the OH group for nucleophilic attack, and the plausible reaction mechanism would involve an intramolecular SN2-type displacement. However, the lower reactivity of the carboxamide oxygen (as an O-nucleophile), together with the comparatively high activation

• literature. The method involves as the key step the microwave-assisted ring closure of thioamido alcohols promoted by PPSE, presumably via an intramolecular SN2-type displacement of the PPSE-activated OH group. The precursors were easily prepared in a three-step sequence from 4-aminobutanol in high overall

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• have been synthesized via solid-phase peptide synthesis and SN2’ reaction on a Morita–Baylis–Hillman (MBH) residue introduced at the N-terminal of a tetrapeptide. This last step takes advantage of the electrophilic feature of the MBH residue and represents a new cyclization strategy occurring. The

• structurally related to these natural peptidomimetics has been used as a promising strategy for the attenuation of bacterial virulence in strains of S. aureus [12][13][14][15]. Herein, we report the synthesis of new sulfide-based cyclic peptidomimetics through the allylic nucleophilic substitution (SN2’) of

• , this is the first report on the participation of MBH residues as electrophilic sites to allow an SN2’-based macrocyclization of peptidomimetics [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Two of these new compounds were able to interfere with the hemolytic activity of S. aureus, and

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

• that the allylic fluorination was achieved by an SN2-type attack of fluoride on an electrophilic Pd(II)-allyl intermediate. One year later, the same author extended this method to a highly regio- and enantioselective fluorination of acyclic allylic chlorides. Compared to the previous process, this

• phenanthroline derivative. This complex was applied to the SN2 fluorination of primary and secondary alkyl bromides, producing the corresponding alkyl fluorides in 40–90% yield (Scheme 26). In 2014, the group of Lalic [69] developed a mild fluorination of alkyl triflates with potassium fluoride catalyzed by a

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• also transformed into compound 10 by reaction with arenes in TfOH (see Scheme 2 and the corresponding discussion). Hydroxy(or methoxy)alkyl-substituted benzimidazoles 3–8 form cations III', V', VII', and VIII', respectively. These species react with arenes, the most probably, in SN2 way to give

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• peracetylated mannose 8 was performed using the mild acidic catalyst, zinc acetate hydrate [33]. The reaction progress was monitored by thin-layer chromatography. Within the first 20 hours compound 9 was the only product and further progress resulted in gradual removal of the remaining acetate groups. The SN2

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

• -hydroxypropyl fragment which could also be derived from the aziridine amide (2R,1'S)-8 (Scheme 28) [19]. N-Boc-protected amine (2S,1'S)-108 was converted to a key 1,3-oxazolidin-2-one (5S,1'S)-109 by trifluoroborate-catalyzed regioselective and stereospecific (SN2 displacement) cyclization. N-Arylation and

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• transient carbocations in reactions taking place in one kinetic step including asynchronous concerted cycloadditions [36] and SN2-type reactions [37]. Moreover, the real existence of transient carbocations – which are not energy minima – predicted computationally has also been recently proven experimentally

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• the oxiranyllithium species upon the addition of the boronic ester. Unfortunately, all attempts to detect or isolate such ate complexes or related oxiranylboronic esters failed so far [38]. The oxiranylborate complex B then undergoes an intramolecular SN2-like process (Matteson-type rearrangement) [14

N-doped carbon dots covalently functionalized with pillar[5]arenes for Fe³⁺ sensing

• Jia Gao,
• Ming-Xue Wu,
• Dihua Dai,
• Zhi Cai,
• Yue Wang,
• Wenhui Fang,
• Yan Wang and
• Ying-Wei Yang

Beilstein J. Org. Chem. 2019, 15, 1262–1267, doi:10.3762/bjoc.15.123

• % (Figure 2c), while the CN-dots solution exhibited stronger emission intensity with 7% QY (Figure 2d). To investigate the application of the as-synthesized fluorescent CCDs in ion sensing, various chlorides of metal ions (Li+, NH4+, Na+, K+, Cu+, Mg2+, Ca2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Sn2+, Hg2

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• thiophenols 14 through SN2 reaction with cyclopropyl bromide (15, Scheme 2a) [2][4] or by SNAr reaction between aryl fluorides 16 and cyclopropanethiol (17, (Scheme 2b) [6]. Although simple and attractive, these approaches usually require harsh conditions such as the presence of a strong base and high

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• formal syn-SN2’ reaction. This is an intriguing observation, since for other TSs a NPP-cyclisation by anti-SN2’ is usually described [40][45][46][47]. This cyclisation mechanism is thought to be the predominant case, giving rise to a more energetically favoured transition state, but occasionally also the

• of the commercial available products (Table S4–S8, Supporting Information File 1) clearly obeys the anti-SN2’ case (Figures S12–S14, Supporting Information File 1). The observation that 15 was obtained as a nearly racemic mixture contrasts the far more selective incorporation of deuterium into the

• ,10Si-cyclisation to E without major rotational changes and also reflects the short distance between HR and C-10 for the 1,3-hydride shift towards the 10Si face leading to F. Intriguingly, the unusual syn-SN2’ ring closure from (R)-NPP leads to the diphosphate moiety (OPP−) being located close to the

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• stereochemistry (anti-SN2’ reaction), which is favoured for a concerted process and is also discussed for other cyclisation mechanisms [24][25][26], the four theoretically possible options for the BbS cyclisation mechanism are narrowed down to two possibilities: Either the reaction takes place via (R)-NPP

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• reported on the reactivity of oxenoids [74][75][76][77], indicating that the reaction of a nucleophile with oxenoid proceeds through an SN2 process [74]. Following the carbocupration of cyclopropene 3 into cyclopropylcopper species, the subsequent oxidation with the amphiphilic lithiated hydroperoxide t

• ). The reaction proceeded for all R1 and R2 groups tested and determination of the stereochemistry confirmed that the oxidation reaction proceeds with pure retention of configuration at the metalated center (intramolecular SN2 reaction or 1,2-metalate rearrangement) [78][79][80]. It should be noted that

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• resonance structures due to the adjacent carbonyl, being therefore, less stable (Scheme 5). Reaction paths analysis The paths for the SN2 N-alkylation reaction of both deprotonated species (oxoquinoline and carboxamide N–H units) using bromoethane were obtained. It is worth highlighting that for each of the

• the oxoquinoline, when compared to that of the carboxamide group. Because of this, the treatment with the base produces the reactive intermediate, the conjugate base resulting from the deprotonation of the oxoquinoline core, probably exclusively, which acts as the nucleophile in the SN2 reaction with

• bromoethane. These results are in agreement with the analysis of the reaction pathways from which we concluded that if the conjugate base of the carboxamide group were formed in the reaction medium, the SN2 reaction would most likely occur in this site, since this reaction would be the kinetic and

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

• addition of cyclopropenylmethylboronates to aldehydes was also reported [25]. A complementary strategy involves the addition of nucleophiles, in particular organometallic reagents, to cyclopropenylcarbinols or their derivatives E, which leads to alkylidenecyclopropanes F through a formal SN2’ process

• leading to zwitterronic intermediates 8 and 8’. This would result in an increase of conformational flexibility thereby facilitating the nucleophilic displacement of the ammonium by the phosphinite through transition states TS1 and TS2 (SN2-type process), respectively. Oxaphospholanium zwitterions 9 and 9

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

• Nucleophilic substitution at silicon is already discussed with SN2 mechanism, following a backside attack opposite of the leaving group, as well as a front side attack near the leaving group [62][63][64][65][66][67][68]. A backside attack at the silicon in dichlorosilane 7 and monochlorosilanol 8 is blocked by

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• with a CN− anion by a simple SN2 reaction. For this purpose, 5-chloromethyl-1,2,4-oxadiazole 1a was reacted with 10 equiv of KCN in CH3CN at reflux, after completion of the reaction on the basis of TLC, surprisingly we obtained a mixture of products 4 (major) and 3 (minor, Table 1, entry 1). This

• Cambridge Crystallographic Data Centre with the deposition numbers 1844118 and 1832133. We propose a plausible mechanism for the transformation of chloromethyloxadiazoles 1 into the title products 3 and 4. Accordingly, the reaction of 1 with a CN− anion gives cyanomethyloxadiazole by simple SN2 reaction

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• and recyclization, rather than species C. Quenching of species Ba with water (high nucleophilicity) affords alcohol Z-4a. The formation of compound 4a in exclusively Z-configuration may indicate that cation Ba reacts with H2O in SN2 manner, keeping in mind that carbon C5 in Ba possesses a large

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• on the above experimental results as well as our previous report on DABCO-catalyzed reactions of cyclic sulfamidate imines with MBH carbonates of isatins [75], a plausible mechanism is presented and depicted in Scheme 2. For the first step, the nucleophilic Lewis base DABCO reacts with 2a in an SN2

• ' fashion to make a very reactive allyl ammonium intermediate 6. The latter further involves in the SN2' reaction with in situ generated carbanion intermediate 1a' forming SN2-adduct 3a. It undergoes an intramolecular aza-Michael reaction in the presence of DABCO, leading to tricyclic product 4a. For the

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• suitable position for PEG linker attachment [13]. From commercially available 2-(2-aminoethoxy)ethanol the amine functionality was Boc-protected under standard conditions to give compound 2 (Scheme 1). Under basic conditions 2 underwent an SN2 reaction with commercially available p-xylylene dichloride to

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• from 4-(n-octyloxy)aniline, seven G-2 melamine-based dendrimers were obtained in 29–79% overall yields. Their iterative convergent- and chemoselective synthesis consisted of SN2-Ar aminations of cyanuric chloride and final triple N-acylations and Williamson etherifications (→ G-2 covalent trimers) or

• interested in the inclusion of 4-aminophenol, playing the role of peripheral unit, in G-0-2 dendritic melamines’ preparation, by applying the classic SN2-Ar amination of cyanuric chloride in iterative-convergent strategies. Depending on several factors such as (i) the variable π-deficiency of the s-triazine

• ascribed the low reactivity of G-1 dendrons D-Cl and D-N

  NH in our SN2-Ar amination conditions to the increased solvation of their (a–a)/(a–a) rotamers (+140–170%, i.e., more than double) compared to those of the (a–a) rotamers of G-0 3 and 2a. In addition to all the above, due to the steric

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• ][83]. A single coupling product was obtained from the reaction of N-(trifluoroacetyl)glutathione dimethyl ester and triethylamine in methanol at 23 °C for 4 h in 80% yield, which occurred via SN2 displacement by nucleophilic sulfur at C-6. Selective hydrolysis of the trifluoroacetyl triester in a

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• ][12]. The standard Mitsunobu reaction involves coupling of an alcohol and a nucleophile in a dehydrative SN2 process activated by a reactive combination of a triaryl- or trialkylphosphine as reducing agent and a dialkyl azodicarboxylate as oxidant. In a redox process, the phosphine species is oxidized

• anomerically modified carbohydrate with inversion of configuration at the anomeric center, according to a SN2 mechanism. Pathway A can also proceed through a SN1 mechanism when the intermediate glycosyloxyphosphonium ion is less stable. Then, it can decompose into the corresponding anomeric oxocarbenium ion

• -configured glycosyloxyphosphonium ions, which are in turn displaced by the nucleophile in the expected SN2 fashion, resulting in a respective anomeric mixture of products (cf. Scheme 2). In contrast to this, the yields of the obtained aryl sialosides strongly correlated with the pKa of the utilized phenols

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• -thiosugar derivatives. We thus developed the first synthetic route accessing the 4-thiosugar derivative by way of bicyclic intermediate 8 from diacetoneglucose (5). Construction of the bicyclic ring of 8 was achieved by consecutive inter-/intramolecular SN2 reactions of the dimesylate derivative 7 obtained

• by intramolecular SN2 reaction at the 5-position by sulfur atom. Secondary, ring contraction from thiopyranose to thiofuranose occurred to produce 5-aldehyde 26. Finally, hydride reduction of 26 gave the 4-thiofuranose derivative 27. The Pummerer-type glycosylation reaction of 5-O-silylated sulfoxide

• reacted with a nucleobase, giving a mixture of α- and β-anomers since the reaction might occur by the simple SN2 reaction. Thus, the reaction proceeded through both paths a and b in method A, but path a was predominant in the reaction of method B [45] (Figure 3). Nishizono et al. applied the hypervalent

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• -membered heterocycles such as thiophenes, furans, and pyrroles. Consequently, numerous multistep approaches to unsymmetrical 1,4-dicarbonyl compounds involving, e.g., SN2-type displacements [1] or highly functionalized substrates such as β-ketoesters [2][3] or β-ketosulfones [4] have been developed