Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• -isobutyrylguanine, N-benzoylcytosine, 6-O-allylhypoxanthine or N,N-dibenzoyldiaminopurine in 53 to 83% yield. The desilylation of the nucleosides 3a–f with tetrabutylammonium fluoride in tetrahydrofuran (THF) led to the formation of six different double-headed nucleosides 4a–f (Scheme 1) [38][39]. The synthesized

• nucleoside 102 with N1-benzoyl-5-ethynyluracil followed by desilylation produced the double-headed nucleoside 104, whereas the reaction of the azido nucleoside 102 with trimethylsilylacetylene (TMS-acetylene) followed by desilylation produced the nucleoside 105 (Scheme 23) [14]. Christensen et al. [31

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• and desilylation, the electrocyclization of 29a proceeded smoothly to afford the desired 4-aminopyrroloquinoline 30a in 68% yield. Subsequently, the cycloamination of 30a in the presence of Pd(OAc)2, Cu(OAc)2, and K2CO3 gave tetrahydroquinoline 31 in 25% yield. However, although attempts were made to

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• oxide ((R)-7b) provided the product (2S,4R)-9i in a much better 8:1 anti/syn coupling diastereoselectivity (Table 2, entry 10). The configuration of the major anti-diastereomer of alkoxyamine 9j was determined by X-ray crystallography after desilylation and hydrochloride formation (see Supporting

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• this method was able to add at moderate temperatures to unreactive alkenes such as butyl acrylate (26) (Scheme 12). Fluoride ions can initiate a chain process, whereby TFDA undergoes desilylation which is followed by a subsequent decarboxylation, and loss of SO2 to form difluorocarbene :CF2 and F−; NaF

• intermediate allylic cation which was the electrophile in a Friedel–Crafts reaction with 159. The subsequent desilylation of the Friedel–Crafts product gave an α-fluorinated ketone intermediate which then reacted with a second equivalent of 159 in a (Z)-stereoselective, chelation-controlled process. Fu et al

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• which was methylated using methyl iodide and lithium diisopropylamide (LDA) to produce (–)-81a in 84% yield. Desilylation of (–)-81a followed by tert-butyldimethylsilyl (TBS) protection of (–)-82a gave ester (+)-83. Compound (+)-83 was converted to (Z,Z)-(+)-84 by using iodination and a diimide

• enyne 127 in the presence of Pd(PPh3)4, CuI, and triethylamine to give (+)-135 in 62% yield. The double desilylation of compound (+)-135 using HF·pyridine in acetonitrile afforded (–)-136 in 91% yield. The semi-hydrogenation of (–)-136 to produce the desired (Z,Z,E)- triene (+)-87 was challenging under

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• produce 135 and 136 in 85% yield in the ratio of 1:1.16. A six-step synthesis from the major product 136 gave lactone 137. This compond was subjected to successive desilylation, OsO4-mediated dihydroxylation and subsequent oxidative cleavage of the C=C double bond with Pb(OAc)4 to give ketoaldehyde 138 in

• the desired 169 carrying two vicinal quaternary carbons. A one-pot desilylation of the newly formed 169 with a trifluoride–acetic acid complex produced the tetraquinane 170a in 89% yield with a 4:1 dr. The conversion of the freshly prepared ketone 170a to 170b was achieved in three steps. Ozonolysis

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• connected asymmetric bowls, as well as atropisomerism, was constructed by Hirao and his two group members, namely Amaya and Kobayashi, starting from the same bromo derivative 82. First it was converted into ethynylsumanene 91 using a Sonogashira-coupling which on subsequent desilylation and Glaser-coupling

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• in a high yield and enantioselectivity (Scheme 5) [17][18]. The Rubottom oxidation [28] of 43 gave a separable mixture of the desired 44 and its C-14 epimer (≈7:1 ratio). The reductive deoxygenation of 44 proceeded via the tosylhydrazone to afford 45, which upon desilylation and alkyne isomerization

• which point an olefination with the Tebbe reagent and the addition of methanol afforded the cyclic ketal as a separable mixture of the diastereomers 68 and 69 (≈4.5:1 ratio). The desilylation of 68 gave the 2° alcohol, which after oxidation and Tebbe olefination afforded the exocyclic olefin 70. The

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• was modified into compound 6 via benzylidene ring opening followed by benzoylation of the free C-4 secondary hydroxy group in 27. The disaccharide imidate 29 was synthesized from 6 by anomeric desilylation to afford 28 that was converted to the corresponding imidate in an excellent yield. The final [2

Recent synthesis of thietanes

• Jiaxi Xu

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

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• mixture of 51 and 52, subsequent Pd/C-catalyzed hydrogenation and tetrabutylammonium fluoride (TBAF)-mediated desilylation yielding the desired tricyclic 54 (83% yield, 98% ee). Overall, the known intermediate 7-oxotriptophenlide 59 was obtained in an efficient, elegant and scalable way in 10 steps with

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• the amount of the chiral Lewis acid catalyst led to a decrease of both the ee and the yield. Desilylation of the 2-isoxazolidine 1 was effected in CHCl3 using catalytic amounts of p-toluenesulfonic acid (PTSA). Though the yield of the in situ-generated 2-isoxazoline 2 bearing the 1,3-oxazolidin-2-one

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• bond c to the cationic center gives rearranged cation 44, the source of the rearranged acetate 39. Ring expansion via migration of bond b in 43 gives the β-trimethylsilyl-stabilized cyclobutyl cation 45, and subsequent desilylation provides cyclobutene (35). Alternatively, cyclobutyl to homoallylic

• 40–60 °C, but degraded slowly to a mixture of other products. The bicyclobutanes 55, 72b, and 72c were quite stable in CD3CO2D at 20 °C, where triflate studies were carried out. The bicyclobutane products 55 and 72 are a result of desilylation of the γ-silyl cations 54 and 74. Why are bicylobutanes

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• selective desilylation and N-debenzylation with simultaneous N-Boc protection and served as a key intermediate for installation of a dimethylhexylene fragment in Julia–Kocienski olefination [56]. Pyrrolidine alkaloids (−)-hygrine ((S)-61) and (−)-hygroline ((2S,2'S)-62) were isolated from many natural

• form a cis-2,6-disubstituted piperidine framework in (2S,3R,6S)-197. N-Methylation of (2S,3R,6S)-197 was accomplished by reductive amination while a selective deprotection provided the hydroxymethyl group in (2S,3R,6S)-198. Swern oxidation, Julia–Kocienski olefination and desilylation gave (−)-(2S,3R

• the (+)-microcosamine A the protected piperidine (2S,3R,6S)-197 served as a starting material and was first converted into the N-Boc derivative while selective desilylation exposed the hydroxymethyl group to give (2S,3R,6S)-199. Oxidation to the respective aldehyde was accomplished with Dess–Martin

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• bis(tri-tert-butylphosphine)palladium(0) the yield increased to satisfying 90%. For conversion into the dicarboxylic acid 3, another change of the general procedure was necessary. Probably because of the extremely electron deficient aromatic system in 12a, desilylation at room temperature led to

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• desilylation. Initial Lewis acids screened either failed to react (PdCl2(MeCN)2), or led to complex mixtures (BF3, YbOTf, TBSOTf). More encouragingly, both AlCl3 and FeCl3 were found to cleave the acetonide 19a at rt, with the TBDPS group only being partially lost (≈15%) in both cases. AlCl3 was observed to

• group strategy led us to TES protection at both alcohols, on the basis that this group should be robust enough to withstand the enolate manipulation chemistry, that desilylation of the secondary TES ether during acetonide removal could be restored in the subsequent tertiary alcohol silylation step, that

• selective 2° over 3° TES ether desilylation should be readily achievable using AcOH [14], and that the remaining tertiary TES ether should be potentially labile enough to be removed under typical transketalisation conditions (TFA/CH2Cl2/H2O (10:20:1), 40 °C, 48–68 h [14], cf, Scheme 1), thereby

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• by an aqueous work-up gave DAG 6a in only 31% yield, together with concomitant acyl migration of the corresponding sn-1,2-diacylglycerol 6a into sn-1,3-diacylglycerol 6a’. Therefore, the desilylation reaction was carried out by stirring 5a and BF3·CH3CN (Scheme 5a). Next, DAG 6a was reacted with 4

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• product 30 carrying an 8-OPMP group was obtained from PMP-protected polyketide 28. The endgame of a total synthesis of seragamide A (2) will have to address the macrocyclisation, desilylation of the threonine moiety, and O-demethylation of the D-iodotyrosine unit of 31. In orienting reactions on small

• scale, desilylation of 31 (TBAF) was a spot-to-spot conversion. Saponification of both the silylated and desilylated methyl esters with LiOH was possible, as long as very mild acidic conditions were applied on work-up. However, macrocyclisation of the TIPS-protected or the desilylated acid did not occur

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• substitution at C3 [63]. As illustrated with the preparation of alcohol 60, the strategy relies on a sila-Morita–Baylis–Hillman reaction between cyclopropenylsilane 59 and 3-phenylpropanal catalyzed by electron-rich tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) [63]. After desilylation, cyclopropenylcarbinol

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• nitrogen was protected as N-Boc to furnish (4R,5R)-47. Under basic conditions the pyrrolidin-2-one ring was cleaved to provide a five-carbon chain of the target molecule. The final steps included esterification, desilylation and selective oxidation of the hydroxymethyl group followed by esterification

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• 2’-position in the reaction mechanism. Having attained nucleoside 6, the synthesis towards the building block for DNA-synthesis continued by subsequent desilylation of this derivative producing intermediate 7 (Scheme 2). DMTr-protection of compound 7 at the 5’-oxygen with in situ prepared DMTr-OTf

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• either by a NIS-mediated or Vorbrüggen nucleosidation yielded in both cases the β-tricyclic nucleoside as major anomer. Subsequent desilylation and cyclopropane ring opening of these tricyclic intermediates afforded the unsaturated 6’F-bc4,3 nucleosides. The successful incorporation of the corresponding

• 6α/β were subjected to the next reaction step, where the simultaneous desilylation and cyclopropane ring opening to the bicyclic fluoroenone 7 occurred. HF-pyridine smoothly facilitated this conversion. At this stage the two anomers of fluoroenone 7 were separable. The configurational assignment of

• -ROESY experiments (Supporting Information File 1). The gem-difluorinated tricyclic nucleoside 12β was then converted into the bicyclic fluoroenone 13 via desilylation and ring-enlargement by short exposure to HF-pyridine. During the following Luche reduction of derivative 13 the benzoyl protecting group

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• fission may also be used to generate different metal derivatives of the nucleofugal anions as equilibrium components. Fluoride-catalyzed, metal-free desilylation admitted carbonyl addition but blocked the retro-addition. Keywords: alkoxide fission; desilylation; fragmentation; retro-addition; reversible

• compounds: Generated through desilylation of 24 (Scheme 6) by tetrabutylammonium fluoride (Bu4N+F−; ≤0.05 equiv), the ion pair 25 was trapped by pivalaldehyde (4) with formation of 7 along with a comparable amount of the alkene 1. However, the primary alkoxide product, as formed by 25 and 4, was supposedly

• desilylation with Bu4N+ F−.

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• Information File 2) of the 3,5-dinitrobenzoate derivative 13, mp 171–172 °C, prepared in two steps (51%) from the metathesis product on reaction with 3,5-dinitrobenzoyl chloride (DNBC) followed by acid-induced desilylation. Thus compound 7b on metathesis produced exclusively triene 11 and accordingly the

• retigeranic acids, the norbornene derivative 16 was chosen. Addition of lithium (trimethylsilyl)acetylide to the lactol 5 followed by desilylation by using methanolic K2CO3 afforded diol 15 (Scheme 4). The primary hydroxy group in compound 15 was selectively protected to produce the silyl ether 16 in 95