Z-Selective semihydrogenation of alkynes via Ni/Lewis acid synergistic catalyzed system using DMF as hydrogen source and solvent

• Lei Kang,
• Haifeng Gao and
• Luo Yang

Beilstein J. Org. Chem. 2026, 22, 1004–1012, doi:10.3762/bjoc.22.79

• frequently exhibit modest stereocontrol. While cobalt-based systems have demonstrated some ability to tune Z/E selectivity, they often rely on ammonia borane as the hydrogen donor, which presents certain atom-economic disadvantages [5][28][29][30][31][32][33]. Clearly, new strategies are needed to advance

• intermediates, yet their combination with nickel catalysts has been little explored in alkyne semihydrogenation. We envisioned that merging nickel’s competence in alkyne activation and hydrogen transfer with a Lewis acid’s capacity to modulate reaction pathways could enhance both selectivity and efficiency

• application in reduction chemistry [45][46]. In this work, we describe a new synergistic catalytic system for the cis-selective semihydrogenation of alkynes, utilizing a Lewis acid together with a nickel catalyst and DMF as the hydrogen source. This method achieves excellent Z-selectivity (up to 98:2 Z/E

Novel macrocycles: from synthesis to supramolecular function

• Veronica Iuliano,
• Carmen Talotta,
• Margherita De Rosa,
• Paolo Della Sala,
• Konrad Tiefenbacher,
• Pablo Ballester and
• Carmine Gaeta

Beilstein J. Org. Chem. 2026, 22, 982–985, doi:10.3762/bjoc.22.76

• biological receptors. Their well-defined cavities, reminiscent of enzymatic active sites, provide an ideal environment for multiple noncovalent interactions with guest molecules, thereby enhancing binding affinity and recognition selectivity [1][2][3][4]. Between 1980 and 2000, calixarenes [5][6

• binding affinity and selectivity that depended on the presence of Lys121. Structural investigations revealed an unexpected binding mode in which, in addition to the peptide-mediated recognition of the BIR domain, the tweezer scaffold established supplementary interactions with the protein surface. These

Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• among chemistry and chemical industry community [1][2][3][4][5][6][7][8][9]. Given this longstanding significance, the development of controlled reduction strategies has diversified to accommodate the distinct reactivity and selectivity. Representatively, complete hydrogenation of alkynes or alkenes is

• achievable reactivity and selectivity [29]. A design for electroorganic synthesis Chemical transformations are inherently governed by the movement of electrons. Consequently, electrochemistry offers a platform in which an applied potential directly controls the electron flow, enable redox processes without

• charge balance. In certain instances, the resulting metal ions may also participate directly in the reaction process. Notably, since electron transfer occurs at the electrode interface, the nature of the electrode material can directly influence both reactivity and selectivity. Nevertheless, such choices

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• , and functional group tolerance. This review summarizes recent advances in the copper-catalyzed hydroamination of alkenes with (hetero)aromatic N–H nucleophiles, emphasizing the mechanistic paradigms and the factors governing selectivity. Keywords: aromatic amines; aza-Michael addition; Cu catalysis

• aza-heterocycles often exhibit attenuated nucleophilicity, distinct acidity profiles, and potential coordination to metal centers, all of which can significantly influence catalytic reactivity and selectivity [20]. Therefore, the development of catalytic systems that can accommodate the unique

• )aromatic N–H nucleophiles. Notably, ligand design has emerged as a powerful tool for tuning the reactivity and selectivity, including control over Markovnikov vs anti-Markovnikov addition and enantioselective induction in selected cases. These developments collectively underscore the unique adaptability of

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• -metal catalysts. This can reveal their selectivity in terms of reaction position(s) in chemodivergent synthesis (Scheme 2c). The present report explores benzocyclization reactions involving sequential C–H/N–H functionalization by a palladium catalyst. Results and Discussion First, the C–H/N–H annulation

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

Beilstein J. Org. Chem. 2026, 22, 882–887, doi:10.3762/bjoc.22.68

• facial selectivity during electrophilic trapping. These findings expand the synthetic utility of α-boryl lithium intermediates and provide insight into the origins of their diastereoselectivity. Keywords: α-boryl lithium; diastereoselectivity; (iodomethyl)cyclopropylboronic esters; ring-opening

• reaction. We were particularly interested in examining cases with alkyl (5) instead of aryl substituents in 2 on C2 (Scheme 2). We initiated the investigation into the selectivity of the transformation with the synthesis of a library of cyclopropylmethyl iodides 5a–i, using our previously reported

• electrophile PhMe2SiCl did not alter the selectivity of the transformation, yielding 6b as a single diastereomer (Scheme 3). The relative configuration of 6b was determined by X-ray analysis of the osmate ester 7b, derived from osmium-catalyzed dihydroxylation (Scheme 3) [38], and the other products were

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• reagent, 1) was used to label the α-amino group of insulin during sequence determination (Scheme 1a). Its selectivity over lysine’s ε-amine originates from the low pKa of the N-terminus, influenced by the adjacent carbonyl group and systematically characterized at ≈6–7 (Scheme 1b) [7]. Building on this

• principle, pH-controlled N-terminal PEGylation has been applied to the labelling of filgrastim, producing Neulasta®, a long-acting chemotherapy support drug [8]. Enhanced N-terminal modification selectivity can be achieved with dinucleophilic residues. Native chemical ligation recruits N-terminal cysteine

• or cleavable leader peptides. C-Terminal labelling typically suffers from modest conversions (≈50% for photoredox strategies). While selectivity has been improved, few approaches are fully specific. For further discussion, see reviews [25][26]. Rebridging agents Protein sidechains frequently form

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• an important role, affecting reaction rates, thermal stability, reaction pathways and selectivity. Various approaches have been taken to quantify these effects. Given the ubiquitous nature of gold(I) complexes LAuX and the fact that in such systems steric effects tend to be negligible, many studies

• and 3. This correlation proved to be of predictive value in the optimisation of product selectivity with as yet untested ligands [26]. Using kinetic competition experiments is a particularly sensitive method for assessing ligand effects in catalysis, since they are able to quantitatively reflect even

• complexes. Both terminal and internal alkynes could be inserted, with a wide variety of functional groups including alkyl, aryl, OH, COOH, amide and aldehyde substituents, but not DMAD. The excellent stereo- and regiochemical selectivity could be explained by a bimolecular mechanism, as confirmed by DFT

Total synthesis of the capsular polysaccharide repeating unit towards the development of a glycoconjugate vaccine against Klebsiella pneumoniae ST512

• Shuo Zhang,
• Ondřej Daněk and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2026, 22, 821–827, doi:10.3762/bjoc.22.64

• . Keywords: glycoconjugate vaccines; glycosylation; oligosaccharides; selectivity control; total synthesis; Introduction The emergence and rapid spread of multidrug-resistant bacteria represent a critical threat to global health [1][2][3][4]. Among these pathogens, Klebsiella pneumoniae has surfaced as a

• by a one-pot Fmoc deprotection, afforded disaccharide 13 in 70% yield over two steps. Complete α-selectivity was observed, which can be attributed to the anomeric effect and the neighboring group participation of the C2-Fmoc group [34]. Two sequential cycles of glycosylation and Fmoc removal

• successfully cleaved the silylidene group, producing pentasaccharide diol 17 in 81% yield. The final stages involved the regioselective installation of an Fmoc group at the C6-hydroxy group, followed by glycosylation with building block 4 to provide hexasaccharide 19 with complete α-selectivity. Global

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• (VII)) to give (E)-1,2-dibromo-1,2-diphenylethylene, selectively (Scheme 1a) [3]. However, MTO is an expensive reagent and a more versatile synthetic method is highly needed. As a simple method, the reaction of diphenylacetylene and Br2 in CH2Cl2 was reported by Glorius in 2007 [4], but the selectivity

• was reported for the Z isomer (Scheme 1b). As another example in 2008, Adimurthy and co-workers proposed the combination of NaBr-NaBrO3 in AcOH in order to prepare in-situ generated Br2, which was reacted with diphenylacetylene to give no selectivity between E and Z isomers of 1,2-dibromo-1,2

• the combination of NBS (N-bromosuccinimide) and FeBr3 in CH2Cl2 was good for the reaction with diphenylacetylene [16][17][18][19] to give 1,2-dibromo-1,2-diphenylethylene with high E-selectivity. The present method has some advantages. First, is mild reaction conditions, and second is stereoselective

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• comprehensive multiparameter optimization, compound Z8 emerged as a lead FXR/ASK1 dual modulator, demonstrating suitable liver microsome stability and high target selectivity. Collectively, compound Z8 holds great promise for the treatment of MASH. FXR agonist activity of all compounds. Results of the dual

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• Information File 1 for a graphical representation of this and TS images directly generated from the computational data). The analogous calculations for 1a and 1b showed a much smaller difference in activation barrier, 1.0 kcal/mol, which is consistent with the lower selectivity observed for that substrate

• selectivity for formation of 26 at room temperature suggests a profile that is more reflective of kinetic control, such that we can argue that 26 forms between 1 and 2 orders of magnitude more rapidly than cyclic products 1a and 1b, such that they are not detectable in the 1H NMR spectra. Further anecdotal

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• enantioselectivity was observed. In a similar study, Wang et al. reported the CuI/TF-BiphamPhos (L3) complex, a new and highly efficient catalyst for the asymmetric 1,3-dipolar cycloaddition reaction [38]. The authors noted excellent reactivity, selectivity, and a wide range of structural variants for various

• /bisoxazoline L19 as a chiral catalyst system, high enantioselectivity (up to 97% ee) and moderate to high exo-selectivity were achieved in the reactions with N-methylmaleimide. The high efficiency of iminoesters as azomethine precursors is due to the high acidity at the enolizable Cα position and the formation

• . Further studies revealed that reactions of deactivated symmetrical dipolarophiles such as dimethyl fumarate, dibenzoylethylene, and fumarodinitrile proceeded with moderate exo-selectivity and good enantioselectivity (72–91% ee) (Scheme 32). Importantly, reactions with unsymmetrically substituted alkenes

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• . Compared with conventional small-molecule inhibitors, PROTACs exhibit notable advantages, particularly in achieving selectivity within highly homologous proteins. The ability to discriminate among members of such families holds broad implications for future disease treatment. In this review, we primarily

• summarize the advantages of PROTACs in conferring selectivity toward highly homologous proteins. This focus will provide a feasible strategy for developing PROTACs that selectively target highly homologous proteins and will ultimately support future therapeutic applications. Keywords: homologous protein

• ; PROTAC; protein–protein interaction; selectivity; ubiquitination; Introduction The cell is the fundamental unit of structure and function in the human body [1][2]. More than 20,000 proteins act in concert to regulate the entire cellular life process [1]. To date, dysregulated protein function has been

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• off-target effects and incomplete or transient CK2 suppression. PROTACs offer an alternative strategy by inducing proteasome-mediated degradation, with potential advantages in potency, selectivity, and duration of action. Herein, a series of CK2-targeting PROTACs has been designed and synthesised. By

• selectivity and well-characterised bivalent binding mode across the ATP and αD pockets. Because a successful degrader must first engage the protein of interest with sufficient affinity, a PROTAC derived from CAM4066 was expected to retain CK2 specificity and achieve kinase-directed degradation rather than

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• . However, nitrene insertion into compound 3 [40] is better predicted by BDE, although the two lowest BDEs are within 0.1 kcal/mol of each other. As noted by Cernak et al. [6], reaction selectivity of this reaction “has a strong dependence on the structure of the nitrene precursor, highlighting the caution

• that must be used when applying simple measures of selectivity prediction in a complex setting.” Compound 4 Vermeulen et al. [41] reported the Fe(DPD)-catalysed oxidation of (+)-artemisinin (compound 4). Similarly to nitrene insertion into cycloheximide (compound 2), the reactive site does not

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• . Selectivity analysis revealed that LC-JD-6 specifically degraded FGFR2 with minimal impact on other FGFR subtypes. Further studies confirmed that LC-JD-6 also efficiently reduced the expression of FGFR2 on the cell membrane surface. In conclusion, this study successfully developed LC-JD-6, a novel FGFR2

• positioned in the solvent-exposed region of the molecule. Given this observation, we selected the aliphatic amine group as a suitable conjugation site (Figure 2a). Previous studies have shown that different linkers exhibit distinct selectivity profiles [31]. Therefore, in this study, novel FGFR2 degraders

• effectively degrade FGFR2 via the proteasomal pathway, while the VHL E3 ligase-based degrader DGY-09-192 is capable of degrading both FGFR1 and FGFR2 simultaneously [40]. These findings suggest that different E3 ligase ligands may influence the selectivity and efficiency of degradation [41]. Nevertheless, due

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• activity and selectivity. The binding energies of Pt 4d in Pt–Fe/DMPSi‒Al2O3 (332, 315 eV) are lower than those of Pt/DMPSi‒Al2O3 (333, 316 eV) and Pt–Ni/DMPSi‒Al2O3 (334, 317 eV) [30]. Thus, the Pt species in Pt–Fe/DMPSi‒Al2O3 is the most electronically negative among the catalysts, which leads to a

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• chiral-2a/meso-2a = 96:4 molar ratio, and the selectivity factor (krel) was calculated to be 754 based on a second-order equation. In all the three substrates examined, the dimerized products, chiral-2, were obtained in >98% ee thanks to the outstanding enantioselectivity. Keywords: cymantrene; kinetic

• appropriate chiral Mo-alkylidene precatalyst, the highly diastereo- and enantioselective kinetic resolution (KR) of the racemic substrates was attained with the krel values ([reaction rate of the fast-reacting enantiomer]/[reaction rate of the slow-reacting enantiomer]; selectivity factor) of up to 96 for the

Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• attached phosph(on)ate anions as powerful new hosts for the amino acids lysine and arginine. In the recent past, we demonstrated that the affinity and selectivity of our lysine-selective molecular tweezers could be improved by attaching natural peptide recognition elements. This could be documented in

• and precisely the natural binding site in the wide 14-3-3-cleft [10]. These examples for designed protein–protein interaction (PPI) inhibitors demonstrated that short but highly flexible linkers are imperative to increase selectivity and minimize entropical penalty. The design was strongly supported

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• [4]resorcinarene hydroxamic acid has also shown a pronounced binding tendency and selectivity for uranyl and proved to be applicable for the determination of uranium in standard and environmental samples [34]. Importantly, more recent studies have demonstrated that pre-organized or cyclic hydroxamate

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• atropisomeric (hetero)biaryls (Scheme 17) [56]. This highly enantioselective C–H arylation of heteroarenes employs a Pd(0) complex with H8-BINAPO L8 as the chiral ligand, enabling the arylation of 1,2,3-triazoles and pyrazoles in excellent yields with great selectivity. This method also facilitates

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• carbamoylmethylphosphine oxides along with enrichment of the extraction selectivity [36][37][38][39][40][41][42][43][44][45]. Even more impressive is the effect from grafting of four urea groups at the wide rims of calix[4]arene macrocycles achieved by reacting p-aminocalix[4]arenes with aryl- or arylsulfonyl isocyanates

• their structures, in which the nitrated aromatic units experience an additional shielding. This may be also responsible for the selectivity of the two-fold nitration of compounds 8 and 9 leading to calixarenes 12 and 13 rather than to their isomers containing nitro groups in the propargylated aromatic

• calixarene core. This correlates well with the above selectivity of nitration observed for calixarenes 8 and 9 and may be tentatively explained by an electron-withdrawing effect of the propargyl groups. However, in the molecular structures of calixarenes 15 and 16, another feature was observed: in both cases

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• carcinoma cells), and T98G (Human glioblastoma multiforme cells). Cytotoxicity was determined by measurement of 50% inhibition of cell growth by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The selectivity index (SI) was calculated for the investigated compounds. The

• cytotoxicity results (CC50, µM) for the investigated compounds and the calculated selectivity index values are presented in Table 1. The compounds 2, 6, and 8 were found to be non-toxic towards all the cancer and non-cancer cell lines investigated (CC50 > 1000 µM). In general, cancer cells form the following

• rows in the order of decreasing sensitivity to the active compounds: HeLa: 1 > 3 > 9 > 5 > 7 > 4 A549: 1 > 3 > 4 > 5 > 7 = 9 HepG2: 3 > 1 > 4 T98G: 3 > 1 It was observed that compounds 1 and 3 showed the highest cytotoxicity against all cancer cells. Compound 1 exhibited the highest selectivity towards

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• ]helicenes. Inspired by the superior selectivity and sustainability of organic electrosynthesis as an eco-friendly alternative to conventional oxidative methods [43][44][45][46][47], we leveraged our electrochemical approaches [48][49][50][51][52], and redesigned the synthons to access a new unsymmetrical