An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• biology of Notum and build target validation to underpin new drug discovery programs. Results: An improved, scalable synthesis of 1 is reported. Key modifications include: (1) the introduction of the C7-cyclopropyl group was most effectively achieved with a Suzuki–Miyaura cross-coupling reaction with MIDA

• group was most effectively achieved with a Suzuki–Miyaura cross-coupling reaction with MIDA-boronate 11 (5 → 6); and (2) C6 chlorination was performed with 1-chloro-1,2-benziodoxol-3-one (12) (6 → 7) as a mild selective electrophilic chlorination agent. 4-Chlorothieno[3,2-d]pyrimidine (3) was either

• efficient step in our sequence and justified further optimisation (vide infra). Suzuki–Miyaura cross coupling of bromide 5 with cyclopropylboronic acid (2.5 equiv) produced 6 in good yield (62–89%) but the product required extensive chromatographic purification. We reasoned that switching from the boronic

Progress in metathesis chemistry

• Karol Grela and
• Anna Kajetanowicz

Beilstein J. Org. Chem. 2019, 15, 2765–2766, doi:10.3762/bjoc.15.267

• catalysts work and decompose, how macrocycles are formed in ring-closing metathesis, etc. Representative examples of these directions have been the subject of the current, third thematic issue on Olefin Metathesis, including highly educative reviews on tandem olefin metathesis–Suzuki–Miyaura cross coupling

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• , samples of m,p’- (13), o,p’- (15), o,m’- (16), and o,o’-quaterphenyl (17) were synthesized as shown in Scheme 3. Suzuki–Miyaura coupling was used to synthesize 13, 15, and 16 from the corresponding aryl bromides and boronic acids [35]. o,o’-Quaterphenyl (17) was synthesized by homo-coupling of 2

• through time-of-flight matrix assisted laser desorption ionization (MALDI–TOF–MS) mass spectrometry, using sulfur as a matrix. Suzuki–Miyaura coupling to form m,p’-quaterphenyl (13) [35]: 4-Biphenylboronic acid (0.18 g, 0.91 mmol) and 1 M K2CO3 (1.5 mL) were added to a 10 mL Pyrex microwave tube. 3

• (400 MHz, CDCl3) δ 7.87–7.85 (m, 1H), 7.76–7.69 (m, 4H), 7.69–7.64 (m, 4H), 7.64–7.58 (m, 2H), 7.57–7.52 (m, 1H), 7.50–7.45 (m, 4H), 7.41–7.35 (m, 2H). Suzuki–Miyaura coupling to form o,p’-quaterphenyl (15) [35]: K2CO3 (0.91 g, 6.6 mmol) and water (7.7 mL) were combined in a 25 mL round bottom flask

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• application in STED (stimulated emission depletion) microscopy, as sensor molecules for, e.g., ions and as fluorophores for the optical imaging of tumors. Different strategies were already employed for their synthesis. Because of just three known literature examples in which Suzuki–Miyaura cross couplings

• functionalized with free acid moieties are directly accessible in contrast to previously described methods. Keywords: cross coupling; fluorescent dyes; near-infrared (NIR) dyes; silicon rhodamines; Suzuki–Miyaura coupling; Introduction Silicon rhodamines are versatile fluorescent dyes that found extensive use

• , we wanted to investigate if these dyes are also accessible by Suzuki–Miyaura coupling. Results and Discussion Optimization of reaction conditions At first we investigated the effects of different catalysts and boron compounds on the synthesis of silicon rhodamine 22 via Suzuki–Miyaura cross coupling

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• reactions of alkynes. Results and Discussion Synthesis of silver(I) complexes Ligand 1 was synthesized in one step, from commercially available 9,10-dibromoanthracene and 2-(methylthio)phenylboronic acid, using a Suzuki–Miyaura cross-coupling reaction. Notably, the yield was low (26%) [55], and the X-ray

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• regioisomeric bromides were also formed, but they were separated by column chromatography on the next step. Bithiophene 11 was prepared in 74% yield by using a Suzuki–Miyaura coupling (catalyzed by PEPPSI-IPr) between boronic ester 9 and bromide 10 [13][14]. Boronation of bithiophene 11 was achieved under

• , AsOTh2, and SyOTh2 (Figure 1) were obtained using a standard procedure for a Suzuki–Miyaura coupling of iodides 4, 5, 7, and 8 with boronic acid esters 9 and 12 (see Scheme 3). Throughout the text, abbreviations “As” and “Sy” denote asymmetric and symmetric substitution patterns, respectively; “O

• esters 9 and 12 (bpy – 4,4’-di-tert-butyl-2,2’-dipyridine; COD – cycloocta-1,5-diene; NBS – N-bromosuccinimide, DCM – dichloromethane). Photoswitchable diarylethenes AsTh1, SyTh1, AsTh2, SyTh2, AsOTh1, SyOTh1, AsOTh2, and SyOTh2 synthesized via a Suzuki–Miyaura coupling. Conditions: 60 °C, argon

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• ) as alkene component had detrimental effects on the yields in the synthesis of 2d, 2f and 2h. Intermediates 5a and 5b were accessible from 3a and 3b via Suzuki–Miyaura or Stille coupling [34]. Biology The influence on deacetylase activity of three human sirtuin isoforms (Sirt1–3) was determined in a

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

• -catalyzed cross-coupling reactions have laid down the foundation of new C–C bond formations [50][51]. A number of Pd-catalyzed organic reactions viz., C–N coupling, amination and intramolecular amidation, cyclization, and Suzuki–Miyaura coupling [52][53][54][55] have recently been reported in the literature

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• could be converted to other derivatives by Suzuki–Miyaura coupling, reduction or oxidation reactions. Keywords: azomethine ylide; cycloaddition; heterocycle; pyrrolidine; stereoselective; Introduction Cycloaddition reactions of azomethine ylides are an important class of pericyclic reactions that give

• ). The adducts could be reduced, oxidised, or could undergo Suzuki–Miyaura coupling to give different substituted dihydro- and tetrahydroquinoline derivatives. Single crystal X-ray structure for 7c. Single crystal X-ray structure for 9. Reaction of ketone 1 with electron-deficient alkenes 2. Reactions of

• ester 4 and amide 5 with electron-deficient alkenes 6. Reactions of ester 4 and amide 5 with N-methylmaleimide. Reduction and oxidation of adducts 9 and 10. Formation of amides 15a and 15b and Suzuki–Miyaura coupling to yield 16. Supporting Information Supporting Information File 322: Experimental

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

• comprising three palladium-catalysed reactions: Sonogashira, Heck and Suzuki–Miyaura (Scheme 37) [113][114][115]. In this methodology, N-arylpropiolamides 128 reacted with aryl iodides 129 and aryl- or styrylboronic acids 130 under microwave activation to yield 3-(diarylmethylene)oxindoles 131 or 3-(1,3

• palladium-catalysed reactions (Scheme 38). The first one is a Sonogashira coupling reaction between the terminal alkyne of propiolamide 128 and aryl iodide 129, which is preferred to the Suzuki–Miyaura reaction between aryl iodide 129 and boronic acid 130 present in the reaction mixture. Then, an internal

• , presumably by changing the anionic character of the palladium complex to cationic in intermediate 135. Finally, the Suzuki–Miyaura coupling of palladium salt 135 with boronic acid derivative 130 would provide the final oxindoles 131 or 132. Finally, is worth mentioning an example of a multicomponent

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• -Tyr motif has been devised. This approach comprises two key steps. The first one involves the cyclization of a linear peptidyl resin containing the corresponding halo- and boronoamino acids via a microwave-assisted Suzuki–Miyaura cross coupling. This step is followed by the macrolactamization of the

• positively charged groups. Due to these structural properties, biaryl cyclic peptides have a great potential to meet the ever-increasing expectations of new drugs. However, their synthesis is viewed as very challenging. The formation of biaryl bonds in peptides has been performed through a Suzuki–Miyaura

• macrolactamization and the intramolecular Suzuki–Miyaura cross coupling. Another crucial issue is the selection of the anchoring point to the solid support. The glutamine residue placed at the southern hemisphere of 1 was chosen for this purpose. Thus, the synthesis of 1 would involve the preparation of the linear

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• the examples shown in Scheme 14 [33]. Nonaflate PM54 underwent a Suzuki–Miyaura reaction to PM55 or a Sonogashira coupling to PM56 under standard conditions. The ethynyl-substituted pyrimidine derivative PM12 could also be employed in C–C coupling reactions as shown by its connection to pyridyl

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• , its isolation should be possible and enable further modification, for example by ipso-substitution with heteroatom electrophiles. The application of the boronic acid in Suzuki–Miyaura coupling should also be possible [30][31]. Growth inhibition experiments against S. aureus showed that HQNO

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• modifications of some of the intermediates – using Suzuki–Miyaura coupling or cycloadditions – before undertaking the oximation step – provided accesses to further α-amino esters. Moreover, other pathways to α-hydroxyimino esters were explored including an attempt to improve the cycloadditions between ethyl β

• -bromo-α-hydroxyiminocarboxylate and various alkylfuranes. Keywords: α-amino ester; α-hydroxyimino ester; [2 + 4] cycloadditions; [2 + 3] cycloadditions; Knoevenagel; nitrosoacrylate; Suzuki–Miyaura; Introduction Our current work on the chemistry of imidazo[1,2-a]pyrazin-3(7H)-one luciferins [1] has

• that will sometime require a specific study. As shown in Scheme 3, the lack or the cost of some more exotic aldehydes 5 were circumvented as we found out that Suzuki–Miyaura carbon–carbon coupling reactions could be achieved with the brominated alkylidenemalonates 13 or 17 as well as the 5-bromofuran

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• and 5e furnishes piperazin-1-ylchromene 12 in 64% yield. Furthermore, as highly methylated flavonoid derivatives [47] and 6-(3,5-dimethoxyphenyl)chromenes [48][49] have been demonstrated to be potent anti-seizure drugs and anticancer agents, respectively, a Suzuki–Miyaura reaction was performed

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• first developed a strategy which constructed natural products 1–4 by uniting the quinolone cores with the side chain by means of an sp2–sp3 Suzuki–Miyaura coupling reaction [8]. Whilst these compounds unfortunately provided no modulation of PQS quorum screening (as determined using a heterologous

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• “OPC4A”, with several electron-deficient tetraalkyammonium salts. As a result of more recent methods developed by us and others employing Suzuki–Miyaura cross-coupling reactions to produce additional functionalized azulenes, the promise of further greater functionalized calixazulenes lies in store to be

• Suzuki–Miyaura coupling reaction of bromobenzene with 5,7-di(Bpin)azulene, which in turn was formed via the exhaustive borylation of azulene with excess bis(pinacolato)diboron (B2pin2) [21]. Cyclocondensation of 5,7-diphenylazulene with formaldehyde produced 5 [22] under conditions similar to those used

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• with Suzuki–Miyaura cross coupling in combination with metathesis (or vice-versa). Several cyclophanes, polycycles, macrocycles, spirocycles, stilbenes, biaryls, and heterocycles have been synthesized by employing a combination of Suzuki cross-coupling and metathesis. Various popular reactions such as

• ; metathesis; polycycles; Suzuki–Miyaura cross coupling; Introduction Transition-metal catalysts are used in metathesis and cross-coupling reactions. Such advances have opened the door for efficient construction of C–C bonds in organic synthesis. These catalysts tolerate diverse functional groups and the

• reaction occurs under mild reaction conditions. Among different metathetic processes, ring-closing metathesis (RCM) [1][2][3][4][5][6] is of a greater interest than cross-metathesis (CM). It is a widely used protocol for the synthesis of unsaturated cyclic systems [7]. Palladium-catalyzed Suzuki–Miyaura

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• coumarin derivative. Rhodium catalysts Carboxylation of aryl and alkenylboronic esters Aryl and alkenylboronic acids or their esters are of interest in organic synthesis because they are commonly used for C–C bond-forming reactions such as Pd-catalyzed Suzuki–Miyaura coupling reactions [50][51][52][53

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• atropselective Suzuki–Miyaura cross-coupling reaction on 3,4,5-tribromo-2,6-dimethylpyridine was studied. Results: Reactions with various amounts of ortho-substituted phenylboronic acids with 3,4,5-tribromo-2,6-dimethylpyridine gave a series of mono- di- and triarylpyridine derivatives which allowed to draw

• presence of a chiral solvating agent. Conclusion: This regio- and atropselectivity may be generally applicable to other arylpyridine systems. A regio- and atropselective Suzuki–Miyaura cross-coupling process has been observed, giving an efficient access to a class of atropisomeric compounds. An opposite

• selectivity using a differently ortho-substituted phenylbornic acid was observed. Keywords: arylpyridines; atropisomerism; cross-coupling; palladium; Suzuki–Miyaura reaction; Introduction Axially chiral biaryls not only subsist in many classes of natural and bioactive compounds [1][2] but also are an

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• immediately obvious application of this bioconjugation to biochemistry and molecular biology as a tool for protein labelling, it could also be used as a convenient tool for peptide chemists in medicinal chemistry programs for modification of peptides. 2.2 C(sp2)–C(sp2) bond formation Suzuki–Miyaura and

Synthesis and characterization of π–extended “earring” subporphyrins

• Haiyan Guan,
• Mingbo Zhou,
• Bangshao Yin,
• Ling Xu and
• Jianxin Song

Beilstein J. Org. Chem. 2018, 14, 1956–1960, doi:10.3762/bjoc.14.170

• 10.3762/bjoc.14.170 Abstract A π-extended “earring” subporphyrin 3 was synthesized from β,β′-diiodosubporphyrin and diboryltripyrrane via a Suzuki–Miyaura coupling and following oxidation. Its Pd complex 3Pd was also synthesized and both of the compounds were fully characterized by 1H NMR, MS and X-ray

• boron atom [25][26][27][28][29][30], meso- [31][32] and β-position [33][34][35]. By using the method developed by Osuka the β,β′-diborylsubporphyrins [36] can be obtained in high yields. A subsequent Suzuki–Miyaura coupling smoothly affords various β-aryl-substituted subporphyrins [37]. Alternatively

• cavities π-extended “earring” porphyrins through the aforementioned Suzuki–Miyaura coupling reaction and subsequent oxidation [38]. In this case β,β′-dibromo/tetrabromoporphyrins and diboryltripyrrane were applied as reactants. We discovered that both the π-extended “earring” porphyrins and the

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• -Arylbenzo[b]quinolizinium derivatives were prepared with base-free Suzuki–Miyaura coupling reactions between benzo[b]quinolizinium-9-trifluoroborate and selected benzenediazonium salts. In addition, the Sonogashira coupling reaction between 9-iodobenzo[b]quinolizinium and the arylalkyne derivatives yielded

• ]quinolizinium derivatives have to be optimized [34][35]. Accordingly, we extended our studies to improve the conditions of the Suzuki–Miyaura coupling towards biaryl-type benzo[b]quinolizinium derivatives 1a–d (Figure 1), namely to apply the alternative base-free Suzuki–Miyaura coupling reaction [39][40][41][42

• ] between the benzo[b]quinolizinium-9-trifluoroborate (3b) and aryldiazonium salts. We focused our attention on derivatives 1a–d because in these cases a direct comparison with the already reported synthesis with a Suzuki–Miyaura reaction is possible. As we are particularly interested in benzo[b

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• their SCS analogues, SNS pincer complexes are poorly studied for their use in coupling reactions. Accordingly, a series of water soluble cationic Pd(II) SNS pincer complexes have been successfully synthesised and investigated in detail for their catalytic activity in Suzuki–Miyaura coupling reactions

• investigation of the mechanism of the reaction revealed that a Pd(II) to Pd(IV) route is the more likely pathway which was further supported by computational studies. Keywords: cationic palladium(II) complexes; Pd(II)/Pd(IV) complexes; SNS pincer complexes; Suzuki–Miyaura; Introduction The Suzuki–Miyaura C–C

• solvents in the presence of an excess of base [1][2][3]. With the drive for the development of environmentally friendly and low cost protocols, a number of methodologies for the Suzuki–Miyaura reaction under aqueous conditions or in neat water have been reported [4][5][6]. This has been achieved via

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• 59 in moderate to good yields. Nevertheless, a two-fold excess of the iodonium triflate is needed to secure a good conversion, a point that limits again the atom-economy of the overall process. Similarly, the group of Liu has described the double Suzuki–Miyaura coupling reaction of cyclic diaryl-λ3

• , gives access to various iodoaminated intermediates that can be subsequently engaged in palladium-catalyzed Suzuki–Miyaura, Sonogashira, or Mizoroki–Heck cross-coupling reactions. Various aryl, alkenyl, or alkynyl substituents can thus be introduced in good to very good yields. When compared to the

• auto-amination process enables to address the issue of chemoselectivity in some cases. For example, the Suzuki–Miyaura coupling allows for introducing a pyridinyl or a furyl ring that are not compatible with the rhodium-catalyzed oxidizing amination reactions. In a similar manner, the group of