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

• with literature data we converted 7 to the free carboxylic acid carrying a TBS-protected hydroxy group at C8 by silylation with TBSOTf/2,6-lutidine, followed by saponification with LiOH. To investigate whether polyketide 7 could be coupled in an unprotected form with the peptide fragment of seragamide

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• on the glycosylation of silylated heterocyclic bases with acylated (halo)ribofuranoses and Friedel–Crafts catalysts. The main advantage of this method is that the silylation converts polar, often poorly soluble, heterocyclic bases into lipophilic silyl derivatives, resulting in homogeneous reaction

• glycosylation (Figure 3). This intermediate is subsequently approached by Nam from the less hindered side. Subsequently, Franchetti et al. [30] modified the above TMSOTf-protocol by introducing the preliminary silylation of the amide group of Nam, a procedure based on the chemistry developed by Vorbrüggen [24

• ]. This approach was also applied to nicotinic acid (1b), for which the corresponding silyl ester 10b was prepared (Scheme 5) [30]. Nam (1a) was silylated to the bis-silylated nicotinamide 10a using 2 equivalents of TMSCl. The silylation was followed by the reaction of the crude mixture with 1,2,3,5-tetra

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

• ketene acetals of (Z)-configuration 57a–l, arising from O-silylation of the corresponding chelated potassium enolates [60], underwent an efficient [3,3]-sigmatropic rearrangement upon warming to room temperature. After an acidic work-up and treatment of the crude carboxylic acids with

• 60 was converted into glycolate 61 under standard conditions and the latter ester was engaged in the Ireland–Claisen rearrangement. Because the gem-diester substitution at C3 increased the acidity of the proton at C2 in substrate 61 [64], silylation of that position took place under the reaction

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

• hydrolysis, formation of methyl ester and silylation to give 7 after separation from the minor diastereoisomer. After selective hydrolysis of the acetal the hydroxymethyl fragment was oxidized and all protective groups were removed to give (2S,3R)-2 as the hydrochloride (Scheme 1). The observed

• )-2 N-Boc protection preceded the cleavage of the oxazolidine ring while silylation of the hydroxy group was necessary before oxidation of the C=C bond (Scheme 9) [58]. Further applications of the ketopinic acid framework as a chiral auxiliary relied on fine tuning of the steric environment around the

• intramolecular lactonization to form 83 by implementation of the Mitsunobu reaction. After opening of the lactone ring with trichloroethanol and silylation of the hydroxy group oxidation at C5 was performed in the usual way to give a pyroglutamate 84. Benzyl or p-methoxybenzyl esters 85a or 85b were next

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• )-geometry of the crotylboronate, while the 2,3-anti relationship can be rationalized by invoking Cornforth-like transition states [40][41][42][43]. Eventually, silylation of the homoallylic alcohol 12b afforded the expected compound 13b in 68% overall yield from 5 after purification, compared to 29% using a

• the syn diastereomer 18 in high stereoselectivity (93:7). After silylation of the free hydroxy group, the cleavage of the PMB ether with DDQ led to alcohol 20 in 77% yield for the two steps. Ring-closing metathesis of diene 21, obtained by O-vinylation of 20, gave the dihydropyran 22 in 53% overall

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

• cytosine was also effected following addition of benzoic anhydride and catalytic DMAP to the crude reaction mixture and extending the milling time. Quantitative silylation of 5′-O-dimethoxytritylthymidine under these conditions was also reported. Prompted by the insolubility of adenosine 5′-carboxylic acid

• generally required longer to achieve complete reaction and yielded the corresponding O6,N2,N2-tri-Boc derivatives with variable recoveries (25–70%). The scope of this reaction was extended to unprotected nucleosides by effecting a one-pot, two-step reaction sequence (Scheme 4). Initial transient silylation

• and carboxylic acid Boc protection using an improvised attritor-type mill. Nucleobase Boc protection via transient silylation using an improvised attritor-type mill. Chemoselective N-acylation of an aminonucleoside using LAG in a MBM. Azide–alkyne cycloaddition reactions performed in a copper vessel

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• (19) readily available by a selective silylation of 1’,2,3,3’,4,4’-hexa-O-benzylsucrose (7) [36]. Aldehyde 20 [37] – obtained by Swern oxidation [38] of alcohol 19 – was reacted with amine 17 to afford the desired amine isolated as acetate 21 in 85% total yield. Removal of the TBDPS protecting group

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• , which in the presence of base (triethylamine or DBU) and trimethylchlorosilane transform into indolo[3,2-b]quinoline derivatives in moderate to good yields. Keywords: carbanions; cyclization; heterocycles; nitroarenes; nucleophilic substitution; silylation; Introduction The indolo[3,2-b]quinoline

• used N-silylated indol-3-ylacetonitrile as a carbanion precursor in the reaction with nitroarenes. Attempts to obtain tert-butyl N-trimethylsilylindol-2-ylacetate via direct silylation of the ester 1c with trimethylchlorosilane was unsuccessful, the product proved unstable and decomposed rapidly. Thus

• , we decided to perform a one-pot reaction in which in situ N-silylation furnished the expected carbanion precursor. Thus, when we treated tert-butyl indol-2-ylacetate (1c) and p-chloronitrobenzene (2a) with triethylamine and potassium tert-butoxide and then added trimethylchlorosilane we obtained

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• silylation [72]. In these reactions, the single electron transfer (SET) is initiated by KOt-Bu/DMF [63][67][69][71] or KOt-Bu in combination with additives such as bidentate diamine ligands [61][62][63][64][65], 18-crown-6 [70] or azobisisobutyronitrile (AIBN) [62][66]. Herein, we report the synthesis of

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

• nitrosoacetals 3 are not halocarbonyl compounds as in the case of oximes 1 and 2, but aliphatic nitro derivatives, which are readily transformed into enamines 3 by double silylation involving an internal redox process [19][20][21]. This allows the preparation of nitrosoalkenes, which are difficult to access by

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• -(trimethylsilyl) phosphonate. It is worth noticing that these silylated phosphonates produced quantitatively phosphonic acid derivatives after water or alcohol (methanol, ethanol) treatment [157]. In this initial work, NMR data indicated that silylation of dimethyl or diethyl phosphonate with bromotrimethylsilane

• the terminal oxygen doubly bonded to the phosphorus atom was indeed the nucleophilic atom that attacks the silicon atom [159]. Regarding the mechanism of this reaction, the oxophilic silylation involving the oxygen atom which is doubly bonded to the phosphorus atom, thus producing the intermediate I

• phosphonate moiety. Finally, it must be noted that BrSiMe3 selectively induced the silylation of phosphonate without affecting ketone, amide, halogenoalkane or alkyne [163]. The preparation of phosphonic acid from phosphonate with bromotrimethylsilane was also applied to methylene-tris-phosphonic acids [164

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• lipophilicity, for instance through sulfation [18], silylation or esterification [19] of the aliphatic hydroxy and phenolic groups found in lignin. Chemical esterification of lignin [19][20][21] or its model compounds [22], using acetic anhydride in organic solvents such as DCM or pyridine have previously been

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• group from a structurally analog of 9 in DCM as the solvent [20], the Pattenden two-step enol silylation/bromination sequence [23] also found effective to produce consecutively the tert-butyldimethylsilyl enol-ether intermediate from trithiazolylpyridine 9. The latter was treated with NBS reagent in THF

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• [25]. Silylation of the C3 hydroxy group furnished thioglycoside 17. Glycosylation of the C5 linker by activation of 17 using NIS/TfOH as the promoter at −20 °C produced mainly β-mannoside 15 (4:1 β:α) [26]. The identity of the β-isomer was confirmed by NMR analysis (1JCH β = 159.0 Hz, see Supporting

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

• Serena Traboni,
• Emiliano Bedini and
• Alfonso Iadonisi

Beilstein J. Org. Chem. 2016, 12, 2748–2756, doi:10.3762/bjoc.12.271

• organic synthesis in view of their compatibility with a wide range of conditions. Their regioselective installation on polyols generally requires lengthy reactions and the use of high boiling solvents. In the first part of this paper we demonstrate that regioselective silylation of sugar polyols can be

• of the silylation approach was significantly extended with the development of unprecedented “one-pot” and “solvent-free” sequences allowing the regioselective silylation/alkylation (or the reverse sequence) of saccharide polyols in short times. The developed methodologies represent a very useful and

• protecting groups are featuring the presence of hindered substituents at silicon such as in tert-butyldimethylsilyl (TBDMS) and tert-butyldiphenylsilyl (TBDPS) groups. Their bulkiness allows in many cases regioselective silyl protection of primary alcohols. Commonly, O-silylation is performed by exposing the

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

• , an alternative approach had to be used to obtain (R)-10. A known procedure based on addition of vinylmagnesium bromide to isopropylidene-protected D-glyceraldehyde followed by silylation and separation of an equimolar mixture of diastereoisomers led to optically pure olefins 21 and 22 (Scheme 5) [51

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

• synthesis of monoesters. Silylhalides are routinely used for dealkylation [25] of BP esters. Moreover, since the dealkylation reaction by silylation favors sterically less hindered methyl esters over other esters [26], we propose that trimethyl monoalkyl esters could offer a simple route for the synthesis

• with relatively high yields (60–78%). The three methyl ester groups were removed with bromotrimethylsilane at low temperature (<0 °C). The removal of the methylesters by silylation was found not to be fully specific and it led always to the silylation of small amounts of the alkyl ester, despite the

• low silylation temperature. This resulted in mixtures of the desired monoalkylester and medronic acid (5–20%) after the hydrolysis of silyl esters. It was evident that a suitable purification method was needed in order to obtain monoesters with sufficient purity. Two strategies were tested for the

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

• is available. The subsequent silylation or acylation of the hydroxy group gives access to a library of diverse NeoPHOX ligands. In this way the steric size and the coordination ability of the substituent at the stereogenic center can be tuned for a specific application. Structural motifs of

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• synthesis of 2,2-difluorostyrenes through Mg(0)-promoted defluorinative silylation followed by fluorine-ion-catalyzed 1,2-desilylative defluorination. Buchwald et al. demonstrated aromatic trifluoromethylation using potassium trifluoroacetate (CF3CO2K), CuI and pyridine under flow conditions. Increasing the

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

• prepared by regioselective reduction of the carbonyl group, silylation of the resulting alcohol and further reduction of the enone moiety. An ensuing transetherification of alcohol 59 with ethyl vinyl ether gave an allyl vinyl ether, which underwent a magnesium perchlorate-promoted [1,3]-sigmatropic

• literature-known procedure [47]. Regioselective reduction with sodium borohydride, followed by dehydration under Mitsunobu conditions and silylation of the tertiary alcohol furnished trimethylsiloxy ketone 78. The ketone functionality was then diastereoselectively reduced under Corey–Bakshi–Shibata

• commenced with the preparation of diol 96 by a palladium-catalyzed hydrostannylation of 2-butyne-1,4-diol (95). Regioselective silylation with tert-butyldimethylsilyl chloride of the sterically less hindered alcohol, iodination and silylation of the primary alcohol with trimethylsilyl chloride gave vinyl

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• of a regioselective O-silylation of the secondary hydroperoxide with the tert-butyldiphenylsilyl chloride (TBDPSiCl), but with our surprise most of the starting material was consumed, and after column chromatography separation only the O-silylated derivative of peroxylippidulcine A, 12, and a small

• stereochemical configurations that have been previously assigned. The key steps are: i) a modified version of the Kornblum–DeLaMare rearrangement, promoted by the O-silylation of the hydroperoxy group, and ii) an highly regioselective and stereoselective reduction of the exocyclic carbonyl group of ketone 14

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• ). Scheme 10 shows selected examples of the α,β-unsaturated lactams and amides that were used for the 1,4-silylation. Overall, the reactions were achieved in both high yields and enantioselectivities with a variety of substrates. In addition to silicon, much work has been done on the asymmetric 1,4-additon

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• alcohol under buffered conditions, while tert-butyldimethylsilyl ether 6h can be prepared by silylation of i-cholesterol 6a with TBDMSCl. Now we report the results of our study on the application of these ethers as cholesteryl donors in electrochemical glycosylation reactions. Results and Discussion The

• –h was prepared including alkyl, aryl, and silyl ethers. Most of the compounds were prepared by solvolysis of cholesteryl p-tosylate in an appropriate alcohol (neat or mixed with dioxane) in the presence of potassium acetate as a buffer. TBDMS ether 6h was obtained by silylation of i-cholesterol 6a

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• modified Appel reaction [17]. The alkynes H can be protected by silylation (J) because only primary alkynes react in the CuAAC (Figure 3). The synthesis commences with 4-hydroxypiperidine (1), which was converted to piperidine-4-one 3 bearing a protected alkyne moiety as well as to piperidin-4-one 5 with a

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• deprotecting the acetyl groups (without affecting the benzoate functionality) by employing acetyl chloride in anhydrous methanol to afford diol 13 [33]. A two-fold silylation and selective mono desilylation afforded primary alcohol 14 which was converted to its corresponding nitrile via the triflate. The