Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• , blocking (94) or removing (95) one of the N–H groups responsible for H-bonding resulted in a dramatic loss of enantioselectivity (7% ee in 94 and 26% ee in 95), while removing both of the N–H groups gave the racemate (1% ee for 96). Interestingly, thioamide 97 also showed a low ee. Replacing the 3,5-bis

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• , Perm State University, 15 Bukireva st., Perm 614990, Russia 10.3762/bjoc.19.87 Abstract It was shown that the reaction of 2-cyanothioacetamides with hydrazine involves both cyano- and thioamide groups, and 3,5-diaminopyrazoles are formed. In the reaction of 2-cyano-3-(dimethylamino)-N,N-dimethylprop-2

• mercaptopurine (Figure 1), containing an intracyclic thioamide group, are antagonists of purine bases and are well known as cytostatic drugs [13]. The thioamide group as an amide isostere is used in medical chemistry to increase thermal and proteolytic stability and improve the pharmacokinetic properties of

• biologically active substances containing amide groups [14]. The presence of a pyrazole core and a thioamide group within the hybrid molecules that we are planning to obtain, allows us to expect both an increase in their activity and the emergence of other types of biological activity, and also high synthetic

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• σ-holes might enhance the reaction’s chemoselectivity. Specifically, they investigated the coupling reactions between diazonium and iodonium ylides and the soft Lewis base thioamide 67 [145], intending to achieve C–S bond formation with the β-dicarbonyl, producing 68 (Scheme 16). They compared a

• reductive elimination of the iodoarene (Figure 16). They found 72 to possess secondary intramolecular halogen bonding between the nitro group and iodine’s proximal (stronger) σ-hole. The reaction initiated by selectively forming adduct 73 between the thioamide and the ylide, which possessed both halogen

• - and hydrogen intermolecular bonds. This adduct decomposed by reductive elimination of the iodoarene via a three-membered transition state (TS), coupling the syn thioamide and β-dicarbonyl ligands to give thiocarbenium ion 74. The authors determined similar activation energies (≈20 kcal/mol) when

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• -tethered thioamide and amide conjugates. The thioamides were generated by employing a three-component reaction of diverse pyrazole C-3/4/5 carbaldehydes, secondary amines, and elemental sulfur in a single synthetic operation. The advantages of this developed protocol refer to the broad substrate scope

• ]. Substituted pyrazoles are also of considerable interest because of their synthetic utility as chiral auxiliaries [32], synthetic reagents in multicomponent reactions [33][34], and guanylating agents [35]. The installation of a thioamide functionality has attracted an immense attention in medicinal chemistry

• synthesized with frequently occurring pharmacophores originating from drug components comes to the conclusion that the thioamide linkage establishes an intriguing class of biologically significant compounds amenable to combinatorial chemistry [43]. This organic functional group is found in vital biological

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzimidoyl chloride from thioamides by desulfurization and chlorination, as well as its application to the synthesis of 2-substituted benzazoles. Keywords: benzazole; bismuth; cyclization; desulfurization; thioamide; Introduction In the production of pharmacologically active compounds, 2-substituted

• conventional methods; a notable alternative is the cyclodesulfurization, where intramolecular cyclization is combined with desulfurization from thioamide analogs such as thioureas, thiosemicarbazides, and dithiocarbamate salts under mild reaction conditions [10]. These synthesis methods are effective for

• desired product 8a in an excellent yield, whereas the N,N-disubstituted thioamide 5 did not react (Table 1, entries 1, 20–22). These results show that N-phenylbenzothioamide (2a) is superior as a C1 unit donor at the 2-position of benzoxazole. Consequently, the best result was obtained when 1a and 2a were

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• ferrocenes with alkynes by using an unprecedented half-sandwich Sc catalyst [36]. Very recently, Shi and Zhang demonstrated a Cp*Co-catalyzed ortho-C–H allylation of ferrocenes assisted by thioamide using allyl carbonates and vinylcyclopropanes as allylating partners [37]. Meanwhile, Zhang and co-authors

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• effective in the decomposition of the inherent stoichiometric six-membered-ring byproduct from the Lawesson’s reagent to a highly polarized diethyl thiophosphonate. The treatment significantly simplified the following chromatography purification of the desired thioamide in a small scale preparation. As

• ; thioamide; thionation; Introduction The transformation of a carbonyl into a thiocarbonyl group is one of the most important reactions in organic synthetic chemistry [1]. Lawesson’s reagent (LR) is widely applied in this transformation, as well as for the syntheses of various sulfur-containing heterocyclic

• potential large-scale preparations. Thioamides are highly attractive molecules in pharmaceuticals, agrochemicals, electronic chemicals, and materials sciences [17][18][19][20][21][22][23][24][25][26][27]. In coordination chemistry, pincer-type ligands containing a thioamide motif were shown to exhibit

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• thioamide nitrogen completely prevents the formation of the thiazole (route a). The rather complicated product isolation procedure of the Eschenmoser coupling reaction (route b) and the long reaction time taken together with problems connected with changing substituents throughout the molecule, encouraged

• us to find better or even universal reaction conditions compatible with all substituents present in both benzene rings (R1 and R2) as well as at the thioamide nitrogen (R3 and R4). In order to achieve the desired product of the Eschenmoser coupling reaction (route b), two main prerequisites must be

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• (Table 1, entry 11 and Table 2, entry 14). Thus solvent-free conditions, a temperature of 88 °C and a thioamide/azide ratio of 1:2.5 are optimal to prepare N-sulfonyl amidine 1c (entry 11, Table 1). Next, these optimized conditions were used for the synthesis of a small library of 1-alkyl-1,2,3-triazoles

• -donating substituents. 5-Arylamino-1,2,3-triazole-N-sulfonyl amidines To further expand the scope of the reaction we continued studying the reaction of 1-aryl-1,2,3-triazole-4-carbothioamides 1e–h with aryl- and alkylsulfonyl azides 2a,c,f. We have found that thioamide 1e did react with benzenesulfonyl

• compound 1e and the product of its rearrangement to 5-(4-nitrophenyl)aminotriazole 1j [54], when the reaction was carried out in n-butanol at 105 °C (Table 2). Therefore, we can conclude that compound 3t was the product of a tandem reaction involving first the rearrangement of thioamide 1e to 1j followed

Recent synthesis of thietanes

• Jiaxi Xu

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

• cleavage and aromatization to give substituted pyridines 255 [75] (Scheme 49). In 1989, Kanaoka and co-workers further studied the photo [2 + 2] cycloadditions of thiobarbiturates 256–258, whose skeletons consisted of a combination of a thioamide and an amide or a thioamide (two-imides system), and olefins

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

• (Table 1, method A, entry 1), was unexpectedly found to be O-benzyl benzylcarbamothioate (4a). The spectral data indicated that the product existed in cis- and trans-geometrical isomeric forms (rotamers) because of free rotation along the thioamide bond. When the same reaction was conducted in other

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

• equivalent 0.5:1 maintained the yield (95%) and considerably simplified the procedure, suppressing collateral products arising from decomposition of the reagent. Under these conditions, compounds 2a–m were synthesized in excellent yields (Table 1). Cleavage of the thioamide-ester 2a with K2CO3 in methanol

• thioamide would overcome the difficulty of the formation of the seven-membered ring, yielding exclusively the tetrahydrothiazepine (Scheme 2, reaction b). Conclusion We have developed a general method for the synthesis of 2-aryltetrahydro-1,3-thiazepines, a heterocyclic core with very few examples in the

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• attempted to involve the simplest aliphatic thioamide, thioacetamide, in the interaction with PBTs 2. As a result, we obtained the expected spiro[thiazolo-5,2'-pyrroles] 3, which were found to exist in a form with an exo-methylene group according to the NMR spectra (Scheme 3) [19]. Unfortunately, the

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• disulfide, thioamide derivatives and sulfides Disulfides and thiosulfates Sulfoxides Sulfinic acids, sulfinate salts and sulfinamides Sulfonyl halides, sulfonyl hydrazines, thionyl chloride and sulfur dioxide C–S bond formations initiated by irradiation with light of wavelengths shorter than 380 nm or by

• furans or pyridines. Thioamide derivatives Formation of benzothiazoles Already in 2012, Li et al. envisioned a photoredox protocol for the synthesis of 2-substituted benzothiazoles applying [Ru(bpy)3](PF6)2 as photocatalyst and molecular oxygen as oxidant (Scheme 31) [66]. As starting material

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• the same molecule. The main objective of our current research was to study Rh(II)-catalyzed reactions of diazocarbonyl compounds with α-cyanothioacetamides, bearing both thioamide and cyano groups in their structure. Based on the known literature findings [36][37][38] one might expect that a catalytic

• tetraoctanoate, the yields of the compounds 3a and 4a comprised 35 and 23% (Table 1, entry 3), while when using dirhodium tetrapivalate they were 48 and 27%, respectively (Table 1, entry 4). Thus the total yield of the main reaction products 3a, 4a increased to 75% (91% based on the reacted thioamide 1a

• ). However, a full conversion of thioamide 1a in these experiments was not achieved in spite of the 1.2-fold excess of diazomalonate 2a used in the process. Further increasing the amount of diazomalonate 2a (up to 2.1 equiv) in the reaction with rhodium tetrapivalate resulted in the enhancement of the yield

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• an additional bromination reaction followed by Bagley’s modified Hantzsch condensation with the adequate thioamide to deliver the fully orthogonally-protected heterocyclic core of GE2270 along with avoiding racemization of stereogenic centers (Figure 1). Successfully applied last year by Yamagushi's

• to give the expected brominated trithiazolylpyridine 17 in 51% yield over two steps. The enantiomerically pure Cbz-protected thioamide 16 was newly synthesized from the commercially available ethyl trans-cinnamate in 7 steps and 27% overall yield following the Nicolaou reported synthetic pathway [24

• ] (Scheme 2). As final stage, the Hantzsch condensation of brominated trithiazolylpyridine 17 with N-Cbz/O-TBDMS-bis-protected thioamide 16 was investigated, inspired by the modified Merritt and Bagley protocol, which was specifically designed to avoid a strong acidification of the reaction and thus prevent

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• -intermediate [76]. After conversion to amide 28 and thioamide 29 the thiazole 31 was obtained by condensation with bromoester 30. The carbamate was then introduced by activation of the deprotected hydroxy group with carbonyldiimidazole and treatment with methylamine, before the ester was selectively reduced to

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• , although substitution at the 1-position prevails. For ethoxycarbonyl isothiocyanate, apart from the 1-substituted thioamide, 1,8-disubstituted thioamide and 2,7-di-tert-butylpyrene-1-carbonitrile are formed (especially at longer reaction times). Keywords: amide; Friedel–Crafts; isocyanate; isothiocyanate

• ; pyrene; thioamide; Introduction Direct functionalization of pyrene 1 has attracted a great deal of attention in recent years because it is the most straightforward route to novel organic molecular materials for optoelectronic devices (OLEDs, field-effect transistors, fluorescent sensors, dye lasers, etc

• , for the reaction with p-methoxyphenyl isothiocyanate we were able to obtain, by crystallization, the major product, C(1)-substituted thioamide 3n, contaminated with only ≈5% of its C4-substituted counterpart. We tentatively explain this poorer regioselectivity by possible π–π interaction of pyrene

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• -workers developed the synthesis of 5-(dibromomethyl)thiazole derivatives 44 by treatment of N-propargyl thioamides 43 with bromine in an ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate). Mechanistically, the reaction involves: i) bromination of triple bond of thioamide 43 which resulted in a

• examples for the preparation of fully substituted dihydrothiazoles 46 through the treatment of N-propargylamides 45 with Lawesson’s reagent in toluene. It is suggested that the N-(propargyl)thioamide intermediate A is initially formed, followed by a facile 5-exo-dig cyclization process to give the final

• (Scheme 13). The proposed mechanism for the reaction starts with the generation of the N-(propargyl)thioamide intermediates A through a thioacylation of N-propargylamine 47 with benzotriazolylthione 48. Then N-desilylation of A furnishes intermediate B which undergoes a base-promoted cyclization to give

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• NMR spectral patterns with the NH protons at similar chemical shifts and they adopt paired thioamide structures (vide infra). The 1H NMR spectrum also shows four doublet and two triplet signals at δ 8.60, 8.19, 7.75, 7.11, 7.88, 7.56, respectively due to eight aromatic protons. The 13C NMR spectrum of

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• of phenolic lipids, we have synthesized novel derivatives of phenolic lipids from undecenoic acid where the phenolic acids were linked to the olefinic group of undecenoic acid via a thioamide spacer. Among the various fatty acids reported, 10-undecenoic acid is unique due to its bifunctional nature

• dichloromethane, washed with water and dried over anhydrous Na2SO4 and concentrated to obtain the crude product. The crude product was purified by column chromatography (chloroform/methanol 90:10, v/v) to obtain the thioamide of cinnamic acid in 86% yield (0.73 g). The product was characterized by 1H and 13C NMR

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• -chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the

• ready access to appreciable quantities of material is required. Preparation of α-thio-β-chloroacrylamides typically results from a three-step synthetic route, culminating in a final cascade/domino reaction [13] where a toluene solution of α-thioamide and NCS is subjected to a ‘hot plunge’ by placing it

• requires significant external cooling, an undesirable feature for scale-up. The synthesis of the α-thioamide 2 involves prior generation of fresh sodium ethoxide from sodium metal. Furthermore, this α-thioamide protocol, at high pH, ordinarily does not go to completion, leaving unreacted starting material

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• organocatalysts ((thio)ureas, squaramides, quinolinium thioamide, etc.) in the literature containing this favored structural core. They have been successfully employed in reactions such as Friedel–Crafts alkylation, Michael addition, Diels–Alder and aza-Henry reactions. However, the 1,2-aminoindanol core

• acting through hydrogen bonding, such as thiourea, urea, squaramide, and thioamide frameworks. These have been efficiently employed in a few organocatalytic processes such as Friedel–Crafts alkylations, Michael additions, Diels–Alder reactions and aza-Henry reactions, as discussed below. Friedel–Crafts

• enantioselectivity, further modifications of the catalytic structure led to highly active catalysts. Indeed, the best results were obtained with the quinolinium thioamide 6, where the NH moiety adjacent to the pyridine ring of the analogous thiourea was “removed”. Likely, in this case, the intramolecular hydrogen

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid

• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Anna Gajda,
• Tadeusz Gajda,
• Anna Makal,
• Arnaud Brosseau and
• Rémi Métivier

Beilstein J. Org. Chem. 2015, 11, 2451–2458, doi:10.3762/bjoc.11.266

• = 0.25) was assigned to π–π aggregates, the presence of which was revealed by single-crystal X-ray diffraction analysis. Keywords: amide; fluorescence; isothiocyanate; phosphonate; pyrene; thioamide; X-ray structure; Introduction Friedel–Crafts-type reaction of arenes with isothiocyanates constitutes a

• isolated in 87% yield. Photophysical properties of 3a–d and 4 As expected, thioamides 2a–d were nonfluorescent (thioamide group is a well-known fluorescence quencher [31]). In contrast, the corresponding amides 3a–d showed strong fluorescence emission in solution and in the solid state. We studied the