(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• alkenes including acrylates, vinyl sulfones, and acrylamides could all be incorporated and the number of accessible bifunctional 1,2-BCHs was increased further by chemical transformation (Scheme 3D) [35]. Among the reported transformations were reduction of the ketone (to (±)-34), hydrolysis of the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• advantages are (i) the universality to a wide range of monomers such as (meth)acrylates, (meth)acrylamides, dienes, vinyl ethers/esters, etc.; (ii) tolerance to unprotected functionalities in monomers and the solvent including –OH, –COOH, –SO3H, etc.; (iii) different reaction conditions, including bulk

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• challenge. In this context, a regioselective alkylation of ortho-unsubstituted or substituted unactivated pyridines with acrylates and acrylamides under Rh(I) catalysis has been demonstrated by Ellman and co-workers [59]. The authors observed that in the presence of [Rh(cod)Cl]2 as catalyst, dppe as ligand

• , and potassium pivalate (KOPiv) as base, linear C–H-alkylated products 40 were obtained from both acrylates and acrylamides in moderate to high yields (Scheme 9, reaction conditions a). However, when K3PO4 was employed as the base under otherwise identical conditions, the authors observed a switch in

• regioselectivity and branched products 41 were obtained with acrylamides as coupling partners (Scheme 9, reaction conditions b). Thus, the authors demonstrated a switch in regioselectivity (linear/branched) which was controlled exclusively by the base used. During further investigations the authors found that the

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• affect the diastereomeric ratio, resulting in even opposite selectivity. Roush and co-workers have presented a simple stereoselective reductive aldol procedure for the synthesis of tetrasubstituted enolates 210 from substituted morpholine acrylamides 209 (Scheme 54) [99]. Subsequent trapping of the boron

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• air or moisture sensitive). Under these mild reaction conditions, a panel of α-(hetero)arylacrylamides were trifluoromethylthiolated in good to high yields. Acrylamides substituted at the α-position by an aryl bearing an electron-donating group (OMe) or halogen (Cl) at the para-position were readily

• acrylamides bearing a disubstituted arene (29g,h) and an heteroaryl (29i) at the α-position were also suitable substrates for this reaction. Finally, acrylamides bearing a methyl group at the α-position (29j) or the α,β-dimethylated acrylamide (29k) were suitable substrates albeit the corresponding products

• catalyst. The same year, Besset and co-workers extended this methodology to a larger class of acrylamides [106]. I.3) Transition-metal-catalyzed trifluoromethylthiolation of aliphatic C(sp3)–H bonds Despite the important progresses presented in the previous section, some limitations of the

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• reactions constitute a powerful synthetic approach to construct multiple C–C or C–X bonds in one pot. As such, these tend to allow facile access to many complex natural molecules and drugs [1][2][3][4][5][6]. Recently, radical-initiated cascade cyclizations involving acrylamides have attracted considerable

• /cyclization cascades from acrylamides for the synthesis of oxindoles [39][40][41]. The radicals are typically generated from alkyl halides [42][43][44], carboxylic acids [45][46][47], simple alkanes [48], alkylboronic acids [49], isocyanides [50], or other [51][52][53]. In this context, the group of Fu

• this decarboxylative cascade cyclization process (Table 1, entries 19 and 20). With the optimized conditions in hand, we then explored the scope of N-arylacrylamides with different substituents. A series of acrylamides showed good compatibility under standard conditions, offering the desired oxindoles

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

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

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• positions, and the two regioisomers 6f and 6f’ were obtained in a 20:1 ratio. The established CN-K-catalyzed cyanomethylarylation protocol is not only effective for the above unactivated alkenes. Also activated alkenes including N-aryl and N-benzoyl acrylamides can be employed as substrates, allowing for

• the construction of valuable oxindole and isoquinolinedione derivatives. With respect to the generality of the N-aryl acrylamides 7 (Scheme 4), a range of frequently encountered functional groups were well tolerated affording the methoxy (8b), methyl (8c), the halogenated (8d–f), trifluromethyl (8g

• , delivering the corresponding regioisomers 8l and 8l’ in 62% with 1:1.6 ratio. Moreover, the naphthalene and tetrahydroisoquinoline-derived acrylamides were also compatible, giving the polycyclic products 8m and 8n in 77% and 70%, respectively. Additionally, protecting groups such as isopropyl, benzyl, or

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• ], fluorination [40], and selenylation [41] have been reported (Scheme 1a). However, the visible-light-induced trifluoromethylthio difunctionalization of alkenes remained underdeveloped. For instance, Magnier and co-workers have documented a practical intramolecular carbotrifluoromethylthiolation of acrylamides

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• 501-1193, Japan 10.3762/bjoc.16.227 Abstract New synthetic methods for spirolactams bearing an α-methylene-γ-butyrolactone or its analogous methylene-lactam have been developed. The allylation of γ-phenylthio-functionalized γ-lactams with 2-(acetoxy)methyl acrylamides was accomplished by using 2.5

• acrylamides 1 in the presence of a catalytic amount of Pd(PPh3)4 to give the corresponding adducts which could be delivered into an methylene-lactam-fused oxindole. On the basis of this umpolung strategy, spirolactams 4 and 5, which are N-alkyl or N-phenyl-substituted analogs of B and C and unable to be

• -lactam structure. The key intermediates were synthesized by electrophilic allylation of γ-phenylthio-functionalized γ-lactam derivatives with 2-(acetoxy)methyl acrylamides in the absence of any metal catalyst and delivered into each type of spirolactams through desulfinative hydroxylation/lactamization

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• sulfonyl radical, prone to start a tandem sulfonylation/annulation of vinyl azides [84]. Recently, the phenanthridine core was assembled through a radical cascade triggered by the trifluoromethylthiolation of N-(o-cyanobiaryl)acrylamides. The process occurred under visible-light irradiation (6 W blue LED

• (trifluoromethyl)thiyl radical, which added onto the double bond of 17.1a–d, and finally delivered the desired products 17.5a–d in good yields, through the intermediacy of radicals 17.3·a–d and iminyl radicals 17.4·a–d [85]. The double bond of acrylamides embedded into a 1,7-enyne framework likewise allowed the

• -cyanobiaryl)acrylamides 17.1a–d. The direct oxidative C–H amidation involving amidyl radicals for the synthesis of phenanthridones. Funding Havall Othman Abdulla is grateful to the Chemistry Department, College of Science, Salahaddin University‐Erbil (Iraq) for financial support.

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

• products (Scheme 26). From the different radical generators screened, dicumyl peroxide (DCP) was found to be very effective in leading to the corresponding products 144–148. Along with different acrylamides, different hydrosilanes were used as silyl source and the reaction could be applied to a wide

• intermediate. This species then undergoes [3,3]-sigmatropic rearrangement, positioning the allylic unit in a regio- and stereospecific manner, along with rearomatization to afford the products 357–360 (Scheme 57) [107]. The borylfluoromethylation of acrylamides, acrylates, and heteroaromatic-substituted alkenes

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• . Nevertheless, most of the known multicomponent methods for the preparation of 2-oxindoles are based on the use of N-aryl amides as the main partner of the reagent pool. Wu et al. reacted N-(2-iodoaryl)acrylamides 113, DABCO·(SO2)2 (69, also known as DABSO) as a surrogate of sulfur dioxide and hydrazine 114 in

• prepared by another type of three-component approach, in this case under copper catalysis (Scheme 35) [112]. The partners of the reaction are N-(arylsulfonyl)acrylamides 123, aryldiazonium tetrafluoroborates 68 and DABCO·(SO2)2 (69), as a source of sulfur dioxide. In this way, sulfonated oxindoles 124 are

• coming from the DABCO·(SO2)2 reagent. Other analogues of acrylamides that are appropriate substrates for oxindole preparation using multicomponent protocols are N-arylpropiolamides. This approach has been reported by Seo and co-workers in a series of papers that develop a three-component transformation

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• highly substituted olefins using acrylamides. However, most of them are limited to one-step coupling or annulation and just a single ring is formed [15][16][17][18][19][20][21][22]. Therefore, it is necessary to explore a new cascade annulation of acrylamides to construct a polyfused-heteroarene skeleton

• 3b in 41% yield. Acrylamide afforded the corresponding indolizinone 3c in 43% yield. Compared to α-substituted acrylamides, β-substituted acrylamides performed the reaction with lower yields under the same conditions (3d–f). It should be pointed out that α,β-disubstituted acrylamides were also

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• developed a novel ring-opening of cyclopropanols 91 with acrylamides 122 for the synthesis of oxindoles 123 (Scheme 30) [110]. A series of desired γ-carbonylalkyl-substituted oxindoles 123 were synthesized between N-phenyl acrylamides 122 and tertiary cyclopropanols 91 through Na2S2O8-promoted radical

• cyclization under transition-metal free conditions. With the addition of a radical scavenger such as TEMPO or BHT, the reaction was suppressed remarkably. In the same year, Dai’s group also reported the ring-opening-initiated tandem cyclization of cyclopropanols 91 with acrylamides 122 or 2-isocyanobiphenyls

• ring-opening and chlorination of cyclopropanols with aldehydes. Ag(I)-catalyzed ring-opening/alkynylation of cyclopropanols with EBX. Na2S2O8-promoted ring-opening/alkylation of cyclopropanols with acrylamides. Cyclopropanol ring-opening initiated tandem cyclization with acrylamides or 2

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• CM-mediated synthesis of functionalized alkenes of various kinds continue to appear. For example, cross metathesis with acrylates [8][9][10], α,ß-unsaturated acid chlorides [11], acrylamides [12][13][14], vinyl sulfones [15], vinylphosphine oxides [16], vinyl phosphonates [17], enones [18], and

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

• derivative 42f, due to the Lewis basicity of the nitro group. These stereochemical outcomes were also observed in the reaction of acrylamides by means of anchimeric assistance. Preliminary studies to identify asymmetric variants indicated that, in the presence of lactate-based chiral iodoarene catalyst 43

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• corresponding coupling products 3aa and 3af in considerable yields. The scope of the reaction with respect to the olefins was also extensively investigated and encompasses acrylates 2a, acrylamides 2b and 2c, styrenes 2f–m and 2-vinylpyridine (2n). In addition, even non-activated allylbenzene 2o and

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• two steps sequence involving first a palladium-catalyzed Heck cross coupling between 2-bromobenzoic tert-butyl esters 9 and 10 with acrylamides 11a–e (69–72% isolated yields, Scheme 2, Figure 2). The subsequent removal of the t-butyl group in esters 12a–e and 13 (Figure 2) was then achieved by

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• -catalyzed trifluoromethylation of N-aryl acrylamides using Langlois’ reagent (CF3SO2Na) as a trifluoromethyl source and water as the reaction medium (Scheme 36). A variety of CF3-containing oxindoles bearing a quaternary carbon center were formed under this conditions. Furthermore, more CF3SO2Na (3.0 equiv

• reported by the group of Baudoin and the proposed mechanism. Trifluoromethylation of benzamides reported by the group of Tan. Trifluoromethylation of heteroarenes and electron-deficient arenes reported by the group of Qing and the proposed mechanism. Trifluoromethylation of N-aryl acrylamides using

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -arylacrylamides para-substituted on their aryl moiety by electron-donating or electron-withdrawing groups were converted into the corresponding oxindoles with similarly good yields. However, the reaction was compatible only with acrylamides bearing methyl or phenyl as R1 and R2 groups; for example, N-acyl and N

• acrylamides were also investigated for the realisation of cascade reactions including a trifluoromethylation step. This was notably the case of unactivated alkenes: Dolbier and co-workers showed that such compounds could be involved in photoredox-catalysed trifluoromethylation reactions, followed by a 6-exo

• /cyclisation of N-arylacrylamides using BiOBr nanosheets catalysis. Photoredox-catalysed trifluoromethylation/desulfonylation/cyclisation of N-tosyl acrylamides (bpy: 2,2’-bypyridine). Photoredox-catalysed trifluoromethylation/aryl migration/desulfonylation of N-aryl-N-tosylacrylamides. Proposed mechanism for

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

•  29b) [51]. A single-electron oxidative free-radical process was ascertained for the generation of CF3•. From enynes, the iodination step was realised by I2, which was formed by a multistep redox process from I2O5. The intramolecular carbotrifluoromethylations of alkenes from acrylamides and

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• the cross product [29]. To our delight, the reaction of 11 with anilide 13c proceeded well under our developed conditions and the CM product was obtained as a single isomer (E-). Only a few successful reports on cross metathesis with Weinreb’s amide of acrylic acid, and N-alkylated acrylamides are

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties

• Maximilian Maier,
• Magnus S. Schmidt,
• Markus Ringwald and
• Christoph P. Fik

Beilstein J. Org. Chem. 2017, 13, 372–383, doi:10.3762/bjoc.13.40

• (meth)acrylate-based compositions, however, is their susceptibility to premature hydrolysis when used in aqueous solutions, especially at pH values <2.5 [15][16]. One strategy to improve the hydrolytic stability is the oxygen-to-nitrogen substitution. The obtained class of (meth)acrylamides is of

• interest in the field of biomedical applications, e.g., for dental materials, artificial cornea, or drug-delivery systems, for which contact with body fluids is inevitable [17][18]. Whilst some of the resulting secondary di(meth)acrylamides end up being solids, tertiary di(meth)acrylamides can be obtained

• as relatively low viscous, highly soluble/compatible liquids [19]. Furthermore, acrylamides are generally more reactive than the respective methacrylamides. Regarding the substitution pattern, N-monosubstituted acrylamides tend to homopolymerize more readily than their N,N-disubstituted analogues [20