The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• reagent of choice for phosphonate ester cleavage, compared with its more and less reactive analogs, iodotrimethylsilane (ITMS) [11][12] and chlorotrimethylsilane (CTMS) [13], respectively. While being one of the most popular methods for the deprotection of organophosphorus esters, the McKenna reaction may

• esters that indicated a more efficient transesterification reaction at this temperature. Depending on the experiment, the progress of the reaction was monitored by 1H and 31P NMR spectroscopy in short intervals. The complete deprotection of the phosphonate ester group in compound 8 and 9 was observed. In

• the mild deprotection of organophosphorus esters. However, the benefits of this reaction are sometimes overshadowed by side reactions taking place when polyfunctional organophosphorus compounds are involved. Here, we evaluated experiments that did not work, the so called “dark data” [21], and we

Recent synthesis of thietanes

• Jiaxi Xu

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

• ) hydrogen chloride salt after the acidic deprotection [37] (Scheme 5). During recent decades, the cyclic thioetherification strategy was widely applied in the synthesis of thietane-based square sugurs (thietanoses), and sulfur-containing glycomimetics of furanoses and pyranoses [38]. The first thietanose

• second displacement was an intramolecular SN2 process performed under mild basic conditions, affording the desired thietane 116 in 92% yield. After deprotection, oxidative cleavage, and reduction, a thietanose 117 was obtained in 63% overall yield. The thietanose 117 was further applied to synthesize a

• into two different dimesylated nucleosides. After the deprotection with Hg(OAc)2 in the presence of TFA, the dimesylated thiols 127 and 130 generated companied with the thietane-fused nucleoside 128 in one case. Further the treatment of the dimesylated thiols 127 and 130 with DBU gave rise to the

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• acid isomers 6 and 7, which were readily separated from each other by chromatography. Deprotection of isomers 6 and 7 gave the individual free amino acids p-(S)-8 and m-(S)-9 [37][38] (Scheme 2). Coupling of one molar equivalent of neopentyl sulfonate ester 10a or trichloroethyl ester 10b with two

• molar equivalents of the zincate of Fmoc-3-iodo-ʟ-alanine methyl ester 11, to form the protected ʟ-4-[sulfono(difluoromethyl)]phenylalanines 12a and 12b, was carried out using 5 mol % (PPh3)2PdCl2 and 10 mol % DIBAL in THF/DMAC 1:1 at 65–70 °C for 6 h. Partial deprotection by alkaline hydrolysis of 12a

• pentafluoro-ʟ-phenylalanine derivatives 24a–c, respectively [41] (Scheme 5). The stereoselective benzylation of (S)-imidazolidinone ((S)-Boc-BMI) 25 with tetrafluorobenzyl bromides 26a,b afforded the benzylated imidazolidinones 27a,b. The acidic hydrolysis of 27a,b with simultaneous deprotection to release

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• decomposed at around 41–42 °C (Scheme 1a). Therefore, we achieved the synthesis of 3a by Pd-catalyzed thienylation of TTF using acetal-protected 8, followed by deprotection using PTSA·H2O and P(OEt)3-mediated cross coupling with 11 (Scheme 1b). The cross-conjugated molecule 4 was prepared in two procedures

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• . The treatment of the glycosylated tripeptides 6a–f and 7a–f with a mixture of TFA, DCM, and H2O (10:10:1) [31] afforded the partially deprotected acids 8a–f and 9a–f in quantitative yields. The final deprotection of both the base-labile acetyl and Fmoc-protecting groups was achieved by the treatment

• with 7 M NH3 in MeOH, which afforded the free glycopeptides 10a–f and 11a–f in good to excellent yields (Scheme 3 and Table 2). Since chromatographic purification of the unprotected glycopeptides on silica gel would have been rather difficult due to their zwitterionic character, our simple deprotection

• peptide coupling reactions and comparison of HBTU and HATU. Final deprotection yields of 10a–f and 11a–f. Supporting Information Supporting Information File 15: General methods, experimental procedures, and product characterization data of the compounds 1a–f to 11a–f. Supporting Information File 16: NMR

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• alkyl and allyl groups were also successfully introduced via the same method. Additionally, the typically applied N-phenyl group in the THIQ substrate could be replaced by the cleavable p-methoxyphenyl (PMP) group and successful N-deprotection was demonstrated. Keywords: C–H functionalization; C(sp3)–C

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction

• based on the reaction of carboxylic acid with N-Boc-protected aliphatic diamine in the presence of activators and then deprotection of the tert‐butoxycarbonyl (Boc) group using trifluoroacetic acid (TFA) [20]. Compared with the mentioned methods, the latter method achieves the higher yield (up to 90

• compound 8. Finally, the piperazinyl amide 4 was synthesized by of N-Boc deprotection. Another procedure for the synthesis of compound 8 involves acylation of compound 9, which was prepared by the reactions of 18β-glycyrrhetinic acid with 1-Boc-piperazine under similar reaction conditions. Compound 8 was

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• isolated as a purple solid in 60% yield. Subsequently, an in situ deprotection of the TIPS group was carried out with a solution of the triptycene-linked porphyrin 14. The polarity of the in situ deprotected product and TIPS protected starting material were very similar so TLC analysis was unable to

• confirm full conversion. For this reason, it may be that the ethynyl bond was not completely deprotected before the next coupling reaction. After the TBAF deprotection step, the second Sonogashira cross-coupling reaction was carried out with the nickel porphyrin 15 [41] under the same reaction conditions

• functionalize triptycene need to be conducted to widen the scope of this unit as a viable scaffold. Experimental General experimental conditions and methods are given in the supplementary material (see Supporting Information File 1 for full details). General procedure 1: (in situ deprotection with TBAF and

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• the obtained compounds has been confirmed by X-ray analysis, which is consistent with the stereochemistry proposed based on NMR studies. Dipeptide analogues of α-fluorinated β-aminophosphonates 15 presented in this publication, after deprotection of the amine function appear to be attractive compounds

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• catalyst (3 mol %) to give the corresponding 1,3-diene intermediate in 85% yield (Scheme 16). The subsequent hydroboration and oxidation to homoallylic alcohol, followed by a palladium-catalyzed Heck cross-coupling, an allylic oxidation with SeO2, mesylation, and deprotection, afforded (−)-galanthamine (13

• affording a protected tetracyclic kempane derivative. The latter was further converted into (+)-kempene-2 (14a) in 91% yield by deprotection and acetylation (Scheme 17). A reduction of the intermediate ketone with lithium aluminum hydride followed by an acetylation finally led to (+)-kempene-1 (14b) and

• the second-generation Hoveyda–Grubbs catalyst (5 mol %, 83% yield), under an ethylene atmosphere. The subsequent regioselective NaIO4-mediated oxidative cleavage of the pendant double bond, followed by the installation of the unsaturated N-butenyl group, oxidation, and deprotection provided the final

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• chiral centers for the synthesis of both enantiomers of disparlure 1 and 3 and monachalure 2 and 4. Compound 14 also offers the possibility of selective modification of one of the substituents as well as sequential introduction of aliphatic chains. After deprotection of the butanediacetal group, diols 5

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• and 5-exo-trig cyclization catalyzed by the photocatalyst [Cu(I)(bcp)(DPEPhos)]PF6. a5 mol % of catalyst and 5 equiv of DIPEA were used. [Cu(I)(bcp)(DPEPhos)]PF6-photocatalyzed synthesis of alkaloids. aYield over two steps (cyclization and TMS deprotection). Copper-photocatalyzed decarboxylative

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• deprotection then furnished 83b in reasonable yields between 68 and 87%. Bis(diphenylphosphine)-substituted imidazoles were also synthesized by Karthik et al. [87] starting from the diiodoimidazole derivative 84. The lithium chloride mediated magnesium/iodine exchange reaction of 84 followed by the addition of

• major isomer (+)-125 was crystallized from (−)-127 using an isopropanol/hexane mixture and confirmed to have R-configuration. The free ligand was obtained by deprotection of the P-center with 1,4-diazabicyclo[2.2.2]octane (DABCO) under refluxing in chloroform for two days at 50 °C. Duplicating the same

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

• -substituted tetrahydro-1,3-thiazepines by MW-assisted cyclization of 4-thioamidobutanols is presented. The acyclic precursors were prepared in high overall yields by an expeditious three-step diacylation/thionation/deprotection sequence from 4-aminobutanol. Microwave-assisted ring closure of 4-thioamido

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• ). Starting from 3,5-disubstituted nitrosobenzene E, consecutive Bayer–Mills and deprotection reactions would lead to the target compound 3 in five steps. Furthermore, by using nitrosoarene E, the selective installment of the amine groups, e.g., via acetamide- and nitro group-carrying intermediates, could be

• achieved [14][15][16]. Such a strategy had already been used successfully in previous syntheses of o-, p-, and m-bis(arylazo)benzenes in our laboratory [14]. However, multiple protection/deprotection steps lowered the atom economy and increased the step count of this strategy. The second approach towards

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• ppm in compound 9). Full deprotection, including the conversion of the 4-azido group into an amino function, was accomplished by hydrogenation of 9 in the presence of palladium hydroxide in a 1:1 mixture of methanol/acetic acid to deliver the target derivative 11 in 30% yield after final HILIC

• groups with concomitant reduction of the azido group afforded the α-anomeric octyl ((4-amino-4-deoxy-ʟ-arabinopyranosyl)methyl)phosphonate 16 in 38% yield. Deprotection of the endo-glycal ester 15 was also investigated. An intermediate enol resulting from hydrogenolytic cleavage of the benzyl ether was

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• (from −40 to −20 °C). Finally, the deprotection module removed the temporary protecting group, such as fluorenylmethyloxycarbonyl (Fmoc) or levulinoyl (Lev), to reveal a free hydroxy group that allowed for further chain elongation in the next cycle. Fmoc and Lev were used as orthogonal temporary

• -step purification and global deprotection [25]. Linear α-(1,6)-hexamannoside 4 was synthesized using six coupling cycles and 6.5 equiv of mannose building block (BB) 1. No deletion sequences were observed and the crude product was purified using normal-phase HPLC to obtain hexamannoside 4 in 55% yield

• , based on resin loading. The doubly branched hexamannoside 5 was assembled using BB 1 for α-(1,6) linkages and BB 2 for α-(1,6)/α-(1,2) branching points. First, the linear α-(1,6)-trimannose was assembled, followed by deprotection of both Lev and Fmoc to reveal three hydroxy groups. Three sequential

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• , acid-mediated deprotection of the Boc group and final coupling to Boc-ᴅ-alanine. Fully protected tripeptides were transformed by base hydrolysis into the free carboxylic acids, followed by activation of the unprotected C-terminus as a SNAc thioester. Subsequent cleavage of the N-terminal Boc protecting

• benzyl protected serine at the Dha site. Following hydrogenolytic deprotection, in situ produced serine EDC adduct was subjected to copper(I) chloride-mediated elimination to give the dehydroalanine derivatives 34a and 34b in good yields. Deprotection of the ester protecting group also proceeded in good

• hydroxide deprotection of the ester in compound 40 provided the free acrylate 41. In parallel, Boc-protected sarcosine 42 was transformed into the SNAc thioester 43 and the Boc group was removed to give 44. Then, both building blocks, 44 and 41, were coupled to give the protected tripeptide thioester 35b in

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• . Further nucleophilic substitution of 174 with allyltrimethylsilane in the presence of a Lewis acid afforded α-alkylated products 175. The highest de was obtained in the case of 175d. The deprotection of 175 with LAH enabled access to α-alkylated pyrrolidines 176 with the release of 177 (Scheme 56). In

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• ) group deprotection in MeOH/CH2Cl2 using TsOH·H2O as the catalyst (Scheme 2). In a conventional triflation (Tf2O, DMAP cat.), 7 was converted into 8 with a yield of 86%. For the synthesis the triflates 9–11 a one-pot demethylation–triflation sequence was followed (Scheme 2). The treatment of biaryl

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• -linked disaccharide (16a) along with 30% β-linked disaccharide (16b). Compound 16a was used for further glycosylation with the trisaccharide acceptor 11 to afford the protected pentasaccharide 17. Once the protected pentasaccharide was at hand, the next challenge was the global deprotection to achieve

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

• ) and their respective carboxylic acids 3 were obtained in good yields based on previously reported procedures (Scheme 2) [35][36]. Starting from Rink Amide AM resin-bound orthogonally protected Fmoc-Cys-(Trt) 4, solonamide analogues were synthesized following stepwise Fmoc deprotection and standard

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• in AcOH, completely deprotection took place and, after purification, aniline 30 was obtained with high purity. Compound 30 was used to introduce the iodine atom through a Sandmeyer reaction to give 28e albeit in low yield. Reductive amination with 7 afforded amine 16e followed by methylation to give

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• base sensitive compounds, which undergo degradation under standard Fmoc deprotection conditions. As it is common for PNAs, our oligomers have an acetylated N-terminus and a C-terminal carboxamide group. After completion of the PNA sequences, the orthogonally protected backbone module [2-(N-Alloc

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• resin followed by filtration and removal of the solvent under reduced pressure, led to precipitation of compound 3-syn, thereby causing problems during the ozonolysis. Thus, dichloromethane was added to the reaction mixture immediately after completed Zemplén-deprotection (as indicated by TLC) without

• Zemplén-deprotection and ozonolysis compound 4-anti was obtained. Purification at this stage utilizing conventional column chromatography was not feasible due to the high polarity of the obtained compound mixture, which contained pyranoid as well as furanoid isomers in their α,β-forms. Thus, per-O