Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• , respectively, followed by the desilylation (TBDPS removal) to yield the title products. The intermediate aldehyde 14 can be synthesized from ketone 17 in a four-step sequence by a stereoselective keto reduction, TBDPS protection, TBS deprotection and an oxidation reaction. The ketone 17 can be easily

• to Wittig olefination reaction with triphenylphosphonium salt of n-nonyl bromide 15 in presence of n-BuLi to produce the corresponding Z-olefin 28 exclusively in 83% yield. Di-desilylation of compound 28 was easily achieved with n-tetrabutylammonium fluoride to furnish the target molecule

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• discorhabdin A (112). In 2006, Honda and co-workers [115] reported the total synthesis of spiro-isoquinoline alkaloid (±)-annosqualine (1). In this report, the substrate 113 was cyclized to form spirocyclic compound 114 via desilylation with TBAF in THF followed by reaction with n-BuLi in hexafluoroisopropanol

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• give the chromium alkoxide L [24]. Finally, the Cr–O bond is cleaved by TMSCl, generating the active chromium salt for the transmetalation and the silyl ether M, the desilylation of which with a fluoride anion results in the formation of a homoallylic alcohol 4. Conclusion The cobalt/chromium-catalyzed

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• were found to be relatively stable under anhydrous conditions and could be readily prepared via Michaelis–Arbusov (M–A) chemistry (Scheme 15) [23][56]. Transfer of crude M–A reaction mixtures to a zirconia ball mill vessel and removal of volatiles enabled the concomitant partial hydrolytic desilylation

• MBM. Synthesis of pyrophosphorothiolate-linked dinucleoside cap analogues in a MBM to effect hydrolytic desilylation and phosphate coupling. Co-crystal grinding of alkylated nucleobases in an amalgam mill (N.B. no frequency was recorded in the experimental description). Preparation of DNA-SWNT complex

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• 1 and 2 were obtained by epimerization at C9. Mixtures of the isomers of 1 were formed in TBAF desilylation of Cinchona 4-TMS-triazole derivatives. Partial isomerisation of 2a into 2b was performed by transient deprotonation using in situ generated sodium methylsulfinylmethylide (Scheme 1). Both

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• groups is accessible for the use as precursors of peptidomimetics. Keywords: amino acid analogous side chains; desilylation; Ellman’s chiral sulfinamide; intramolecular Huisgen reaction; peptidomimetics; propargylamines; rearrangement to α,β-unsaturated imines; Introduction Terminal alkynes display an

• assume that strong bases do not only lead to desilylation, but also induce decomposition of the propargylamine system (see below). Kracker et al. recently demonstrated the substitution of the labile tert-butylsulfinyl group of compounds 7a–c by the more versatile Boc protective group in yields of 56–94

• imine 5h) after desilylation with TBAF (Table 2). As the benzylic proton of sulfinylimine 5h is quite acidic, approach II was not pursued for the synthesis of propargylamines analogous to tyrosine, histidine, tryptophan, and aspartate. Proteinogenic amino acids do not contain substituents, which

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• reaction with trimethylsilylcyanide in the presence of triethylamine as catalyst (Scheme 32) [81]. Interestingly, the initial addition products are intercepted by TMSCN forming stable TMS ethers of α-cyanooximes 87, which can be isolated by vacuum distillation. Mild desilylation of 87 initiates the

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• + 2]-cycloadduct 8, which only at ca. −40 °C extruded N2 [23]. The goal of the present study was the preparation of a series of 2-trimethylsilyl-1,3-dithiolanes of type 6, which, after desilylation, should be applied for nucleophilic additions of the 1,3-dithiolane anion with some electrophilic agents

• the reagents in a ratio of 3:1. Under these conditions, 1,3-dithiolane 6a was formed almost exclusively with only traces of 1,4-dithiane 7 as revealed by 1H NMR analysis of the crude reaction mixture. Desilylation of 6a occurred quantitatively and the known tetraphenylethylene (9a) [26] was obtained

• desilylation conditions differs significantly from that of 4,5-unsubstituted 1,3-dithiolane 13c (Scheme 5). In the latter case, the desilylation leads to the corresponding carbanion, which can be trapped with an aldehyde to give 14 [24][25]. In contrast, the carbanion 11 undergoes a spontaneous cycloreversion

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• these compounds and notably reported that TES was better than TMS for efficient separation of both isomers, resulting in an improved 42% yield for the isolated major diastereomer (5’R)-11ab [12]. Then, subsequent acidic hydrolysis afforded (5’R)-16 and (5’S)-16 and alkyne desilylation under basic

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• . With 15–21-mer oligomers, some support-bound material, however, remained in solution and was recovered by adsorption to C18-coated silica gel. The cycle was completed by detritylation with DCA (3%) in DCM. Cleavage and deprotection was conventional: ammonolysis in aqueous EtOH, followed by desilylation

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• desired (Z,E,Z)-configured triene 19. Again, we did not encounter formation of stereoisomers in the triene unit. The configuration of the triene was unequivocally assigned by analysis of coupling constants (J) and by measuring nuclear Overhauser effects (nOe). Finally, desilylation and global

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

• (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

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• 1,2,3-triazoles [50]. After the desilylation of syn-5 using potassium fluoride in methanol (Scheme 8) the resulting mono-substituted alkyne was subjected to an established protocol using benzyl azide, copper(I) iodide, triethylamine and TBTA [51] (for a recent review see [52]). The cycloaddition

• . Cross-coupling reaction of 1,2-oxazine anti-4d leading to 5-cyano-substituted 1,2-oxazine anti-25. Desilylation of 1,2-oxazine syn-5 and subsequent click reaction with benzyl azide leading to 5-(1,2,3-triazolyl)-substituted 1,2-oxazine syn-26. Hydrogenation of 1,2-oxazine syn-21 leading to γ-amino

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• ]. After desilylation followed by protection of the free hydroxy with a benzoyl group and deprotection of the isopropylidene moiety, diols 20 and 24 were obtained. With α,β-unsaturated ketones 17 and 18 and two enantiomeric, optically pure aldehydes (R)- and (S)-10 in hand, we started to study the 1,4

Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• before the purification. Conclusion Mixed tetraesters of medronic acid were prepared with relatively high yields (60–78%) and used as starting material for the synthesis of monoesters of medronic acid. A series of medronic acid monoesters were synthesized by using a silylation and desilylation procedure

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• , decreasing in the series t-BuMe2Si > Et3Si > Me3Si. It has been shown that Ir-hydride complexes that are formed as intermediates during hydrogenation are strong Brønsted acids [32], which can cause cleavage of trimethylsilyl ethers under hydrogenation conditions [33]. So partial desilylation liberating a

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• length via stereospecific nucleophilic displacement of the chiral auxiliary with complete inversion of configuration at the sulfur center [46][47]. Sulfoxide 3 is incorporated into the catalyst via a [3 + 2] oxidative cycloaddition with allylruthenium complex 4. Desilylation of cationic complex 5, ion

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• -dimethylimidazolone 4 (R1 = R2 = Me) in the presence of catalyst C1 afforded, after desilylation, the Michael adduct 30 in good yield (74%) but in moderate enantioselectivity (−84%). Improved selectivity (91%) was observed using C2 in the reaction with 4 (R 1= R2 = Me) and even better enantioselectivity was obtained

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• give 61. A sequence of desilylation and oxidation furnished the acid 62. Peptide coupling with amine 63 and acidic deprotection then afforded the desired aldehyde 64, which already contained the muraymycin linker unit (Scheme 8) [107]. Together with the uridine core structure 50 and the urea dipeptide

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• included the second indole moiety of raputindole A (1). Boc protection of 6-iodoindole (2) [35], Sonogashira reaction of 3 with TMS-acetylene, and desilylation gave the N-protected alkynylindole 4 in excellent yield (Scheme 2). Boc-iodoindole 3 was also the precursor of the coupling partner, ketone 6

• Chancellor and coworkers [42], gave nitrophenol 11 in a reasonable yield (45%). The Batcho–Leimgruber protocol failed for nitrophenol 11 [43]. However, after O-benzylation of 11 to 12, Boc-indole 15 was obtained in the very good yield of 91%. Coupling with TMS-acetylene was followed by desilylation to obtain

• PMB group, because the oxidation potential of DMB ethers is lower and the cleavage was expected to be more facile [45]. Indole synthesis from DMB-protected 13 and subsequent Boc protection afforded 16 (58%). Alkynylation and desilylation of 16 to 19 and coupling of 19 with ketone 6 proceeded smoothly

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• parameters was investigated, involving the selection of base and solvent. However, none of the attempted conditions gave the desired product. Instead, desilylation of 3-iodo-1-(triisopropylsilyl)-1H-pyrrole was observed during the reaction, and some of the dimethoxystyrene could be recovered (for details

• expected to have different electronic properties. After desilylation, compound 3c was obtained in a combined total yield of 35% (sum of cis-3c and trans-3c) from the pyrrole-3-carbaldehyde. To obtain trans-4c selectively, a Wittig–Horner reaction was investigated, with dimethoxybenzyl bromide as starting

• 3-bromo-1-(triisopropylsilyl)-1H-pyrrole resulted in low yield (20%) and also homocoupling. Considering that desilylation of triisopropylsilyl protected pyrrole might occur at high temperature in DMF, an overnight reaction at room temperature was performed, resulting in a yield for 4d of 50%. In

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• alcohol was converted to the corresponding silyl ether. Next, alkylation of the metalated sulfone with allylic chloride 51 afforded alcohol 52 after desilylation. Subsequent desulfonylation with sodium amalgam and Jones oxidation of the primary alcohol furnished carboxylic acid 53. The corresponding

• product 63 in very good yield, however, as a mixture of lactol epimers (α/β ≈ 56:44). Silyl protection of the lactol and subsequent Tebbe olefination [42] of the ketone group installed the exocyclic double bond of the nine-membered carbocycle. Desilylation followed by oxidation with silver carbonate then

• acetylide to the carbonyl group of 69, followed by desilylation under basic conditions gave rise to (±)-ethynylcarbinol, which was separated by chiral HPLC. The desired diastereomer was then transformed to benzene sulfinate ester 70. A palladium-catalyzed [2,3]-sigmatropic rearrangement formed an isomeric

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• in CuAAC reactions, copper(II) triflate is known to form protic acid in solution, which could cause proto-desilylation [36], but this is not observed. A broader range of green alcohol solvents [37] were assessed in the presence of the most active catalyst, in situ reduced Cu(OTf)2. Isopropanol was

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• 26, which was subsequently converted to the cyclophane 28 by a Mannich-type condensation reaction (40%) (Scheme 1). Michael addition: In 1999, Reißig and co-workers [85] have synthesized a functionalized cyclophane by a cascade reaction, which proceeds with desilylation, ring opening, proton transfer

• -diiodobenzene with an excess amount of triisopropylsilylbutadiyne (47) followed by complexation with Co2(CO)8 furnished a pale yellow diyne 48. Exchange of the ligand with bis(diphenylphosphino)methane (dppm) afforded a bridged complex which is stable to fluoride ions. Subsequent desilylation, followed by