The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• olefination. Installation of the phosphonate and desilylation gave 76, which, after oxidation, reacted in the presence of sodium 2,2,2-trifluoroethanol (NaOTFE) in 2,2,2-trifluoroethanol (TFE) via an intramolecular Horner–Wadsworth–Emmons reaction to 77. Cytochalasin L-696,474 (78) was obtained from 77 via

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• -catalyzed cycloisomerization proceeded uneventfully (Scheme 3). Desilylation of allenes 6a and 6b with tetrabutylammonium fluoride trihydrate afforded the α-hydroxyallenes 7a/b in high yield, and these were converted into the aminoallenes 8a/b under standard Mitsunobu conditions (DEAD, PPh3, phthalimide

• ; then hydrazine monohydrate) [38][39][62]. Unfortunately, fluoride-mediated desilylation of allene 6c caused complete epimerization of the allenic chirality axis. Therefore, the silylallene was not used in further studies. The results of the gold-catalyzed cycloisomerization of the allenes 7 and 8 to

• . Fortunately, the correct stereoisomer was enriched at the stage of the dihydropyrrole 18 due to several purification steps. Desilylation of 15 with tetrabutylammonium fluoride trihydrate (94% yield) and conversion of 16 into the α-aminoallene 17 under Mitsunobu conditions (45% yield) [38][39][62] set the

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• with methyl chloroformate and DMAP. The allylic carbonate 15 underwent efficient asymmetric allylic amination [20] with o-nitrophenylsulfonamide as the nucleophile to give the allylic sulfonamide 17 in 66% yield; in addition, the linear product 16 was also obtained in 7% yield. Desilylation of 17 (→ 18

• (Table 4) were obtained after removal of the fluorous tag by desilylation. Conclusion Metathesis is an extremely powerful reaction for diversity-oriented synthesis. It was demonstrated that metathesis substrates could be assembled efficiently from triplets of building blocks. Thereafter, metathesis

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• -membered 25 was induced by treatment with NaNO2 in acetic acid [28][29], resulting in the formation of eight-membered 27 through the intermediary of 26. Finally, the desilylation of 27 with TBAF and the subsequent oxidation of the resultant hydroxy group delivered the symmetric diketone 1 in optically

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• , because partial silyl migration to the free hydroxy groups was observed while attempting mono-desilylation. Synthesis of three-unit spacers To obtain the three-unit spacer, the odd strategy (Figure 4) was applied starting with compound F. In order to make F, the silyl protecting groups of both 4 and 6

• their affinity for the target proteins, but can create solubility problems. Desilylation of 13 (TBAF, THF, Scheme 7) followed by in situ CuAAC with the pseudo-disaccharide 23 led to the divalent ligand 24, which was found to be fully soluble in water, at least up to millimolar concentrations. Compound

• of this nature. It was also shown that the three-unit spacer 13 could be used in a one-pot desilylation and CuAAC reaction to give 24, which was found to be fully soluble in water, despite the more lipophilic nature of the active ligand. This finding paves the way for the synthesis and evaluation of

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Determination of the relative configuration of tropinone and granatanone aldols by using TBDMS ethers

• Ryszard Lazny,
• Aneta Nodzewska,
• Katarzyna Sidorowicz and
• Przemyslaw Kalicki

Beilstein J. Org. Chem. 2012, 8, 1877–1883, doi:10.3762/bjoc.8.216

• obtain the free aldols in the endo forms by TBDMS deprotection. Under the typical desilylation conditions (1 M TBAF in THF) no formation of aldols, but rather products of their decomposition were detected in the resulting complex reaction mixtures. The presence of a relatively acidic pseudoaxial hydrogen

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• -difluorobenzenesulfonyl chloride were sulfonylated with cyclopropyl amine followed by Mitsunobu alkylation with 3-silyloxybutan-1-ol and subsequent one-pot desilylation intramolecular SNAr alkoxylation (Scheme 2). Each of the scaffolds 1–8 was prepared on a 2.5 g scale. With scaffolds 1–8 in hand, efforts were focused on

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• completed the synthesis of 1, the reported structure of cephalosporolide H. The opposite spiroketal isomer 1a was prepared from 6 by palladium-catalyzed cycloisomerization (steric control), desilylation and TEMPO oxidation. In neither case did the characterization data match that of the natural material

• alkyne 5 with (S)-1,2 epoxynonane. Gold-catalyzed cycloisomerization (with desilylation) provided spiroketal diols 10a and 10b in a 32:68 ratio and in 89% total yield. Major spiroketal 10b could be converted to 10a in 15:1 dr by zinc-catalyzed isomerization. Both isomers (10a and 10b) were independently

• silyl ether 19 with the (R)-propylene oxide produced the internal alkyne 20 (Scheme 5). Gold(I) chloride in MeOH induced the spiroketalization of alkyne 20 with concomitant cleavage of the PMP acetal and partial cleavage of the TBS ether. After completion of the desilylation with TBAF, a mixture of 5,5

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• provide a method to prepare fused tricyclic products with all ring-junction protons, we carried out the transformations shown in Scheme 8. Desilylation of 20 and 21 gave the alcohols 24 and 27, respectively. Swern oxidation then gave the aldehydes 25 and 28. Finally, using Wilkinson’s catalyst, we were

Pseudo five-component synthesis of 2,5-di(hetero)arylthiophenes via a one-pot Sonogashira–Glaser cyclization sequence

• Dominik Urselmann,
• Dragutin Antovic and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1499–1503, doi:10.3762/bjoc.7.174

• yields, resulting in an increased formation of byproducts already during the desilylation and the oxidative coupling step (as monitored by TLC). A lower reaction temperature resulted in a prolonged reaction time under microwave conditions to achieve complete conversion (Table 1, entry 5), whereas

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• , desilylation of 69 (TBAF) furnished an alcohol that, contrary to the parent 69 or other TIPS-protected synthetic intermediates, exhibited no atropisomerism (single compound by 1H and 13C NMR). Oxidation (IBX) and treatment of the emerging ketone 74 with 48% aqueous HBr in AcOH under reflux afforded synthetic

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• precursor 49 in situ through a Pd/Cu mediated coupling reaction between (trimethylsilyl)acetylene (TMSA) with an aryl iodide, followed by a desilylation reaction. The subsequent addition of the third partner, an o-iodoanilide derivative, allowed a Pd/Cu tandem C–C/C–N-bond-forming reaction. The main

• . Synthesis of indoles through a sequential C–C coupling/desilylation–coupling/cyclization reaction. Synthesis of indoles by a site selective Pd/C catalyzed cross-coupling approach. Synthesis of isoindolin-1-one derivatives through a sequential Sonogashira coupling/carbonylation/hydroamination reaction

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• provide dihydropyridine 6. Elimination of trimethylsilanol and subsequent O-desilylation affords the 4-hydroxypyridine 7 (Scheme 1). The desired β-ketoenamides 4 are either accessible by acylation of enaminoketones or by a multicomponent reaction of lithiated alkoxyallenes, nitriles and carboxylic acids

• , whereas the pyridinol tautomer is favored when a hydrogen bond-donor is present. Compound 37 exists exclusively as pyridone tautomer, but after desilylation the resulting product, with a free hydroxy group in the side chain, strongly prefers the pyridinol tautomer. It seems reasonable to assume that the

• 22 could be O-methylated in good yield with methyl iodide in THF, the same conditions converted 30 into 55 in a disappointing 30% yield. Desilylation of 53 and 55 with HF in pyridine gave the desired deprotected pyridine derivatives 54 and 56 in high yields. This type of enantiopure hydroxymethyl

High chemoselectivity in the phenol synthesis

• Matthias Rudolph,
• Melissa Q. McCreery,
• Wolfgang Frey and
• A. Stephen K. Hashmi

Beilstein J. Org. Chem. 2011, 7, 794–801, doi:10.3762/bjoc.7.90

• structure of 28a. Catalysts 34, 35 and 36. 1H NMR spectra of the separated diastereoisomers of the substrates for catalysis 28 (left) and of the products 37 (right, the small signals are due to the deprotected compounds 38). Structure of the desilylation product 38. Mechanism of the furan–yne reaction

Gold-catalyzed alkylation of silyl enol ethers with ortho-alkynylbenzoic acid esters

• Haruo Aikawa,
• Tetsuro Kaneko,
• Naoki Asao and
• Yoshinori Yamamoto

Beilstein J. Org. Chem. 2011, 7, 648–652, doi:10.3762/bjoc.7.76

• formation of 3a. It is well known that concerted pericyclic ene-type reaction of silyl enol ethers with electrophiles, such as aldehydes or ketones, gives functionalized silyl enol ethers without desilylation [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. To the best of our knowledge, however

Gold-catalyzed regioselective oxidation of terminal allenes: formation of α-methanesulfonyloxy methyl ketones

• Yingdong Luo,
• Guozhu Zhang,
• Erik S. Hwang,
• Thomas A. Wilcoxon and
• Liming Zhang

Beilstein J. Org. Chem. 2011, 7, 596–600, doi:10.3762/bjoc.7.69

• example, allenes derived by replacing the acetoxy group of 1b with a free OH or an OTBS group did not lead to the desired products. Presumably, the nucleophilic OH group in the substrate, or one generated via acidic desilylation, interfered with the reaction. This reasoning was supported by the isolation

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• reaction time was intentionally extended to ensure complete desilylation. A second mechanistic alternative, path b, cannot be ruled out at this time. Path b involves gold-activation of the alkyne followed by 5-exo-dig nucleophilic attack of the acetal oxygen. Methanolysis of the acetal and spirocyclization

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

• Yu-Hsuan Wang,
• Joshua F. Bailey,
• Jeffrey L. Petersen and
• Kung K. Wang

Beilstein J. Org. Chem. 2011, 7, 496–502, doi:10.3762/bjoc.7.58

• with iodine [7]. 1-Ethynyl-2-iodo-benzene (15) [30] was prepared in quantitative yield by desilylation of 1-iodo-2-[2-(trimethylsilyl)ethynyl]benzene with sodium hydroxide in methanol. 1-Ethynyl-2-(methoxymethyl)benzene (4b) [31] and dimethyl (1-diazo-2-oxopropyl)phosphonate [32] were prepared

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• remaining hydroxyl groups afforded the glycoside 13, which was desilylated with HF·pyridine complex to yield 14. This chemoselective transformation uses conditions that are similar to those reported by Tam et al. [23], and result in desilylation in a significantly shorter period than that previously

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• thioglycoside 4 [14] yielded the 6-O-silylated compound 5 (92%), benzylation of which gave donor 6 (85%). A benzyl group in the 4-position was preferred to an ester group to avoid the risk of acyl migration during subsequent reactions; desilylation, glycosidation and phosphorylation. 3II,4II-Diols of lactose

Polar tagging in the synthesis of monodisperse oligo(p-phenyleneethynylene)s and an update on the synthesis of oligoPPEs

• Dhananjaya Sahoo,
• Susanne Thiele,
• Miriam Schulte,
• Navid Ramezanian and
• Adelheid Godt

Beilstein J. Org. Chem. 2010, 6, No. 57, doi:10.3762/bjoc.6.57

• synthetic routes have emerged: The repeating unit by repeating unit approach (Scheme 1a) with desilylation and coupling of the (functionalized) arylethyne with 1-iodo-4-(2-trimethylsilylethynyl)benzene as the two repeating steps [6][9][20][21][22][23][24]. The oligomer grows slowly repeating unit by

• -trimethylsilylethynyl)benzene is the parent compound. Desilylation and exchange of the triazenyl substituent for an iodo substituent are the two divergent steps followed by the alkynyl–aryl coupling, the convergent step. The dialkyltriazenyl group decomposes during chromatography on silica gel [28]. The divergent

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• hydrogenation, desilylation and removal of the butane diacetal group finished the total synthesis of 134. The spectroscopic data for synthetic 134 (1H NMR, 13C NMR, IR, MS, mp and specific rotation) were in excellent agreement with those reported for naturally occurring muricatetrocin C (134). In 2002, the full

• . Oxidative release of 160 followed by Swern oxidation and Takai reaction provided the terminal vinyl iodide 161. Final Pd0-catalyzed coupling of alkyne 157 with vinyl iodide 161 gave the enediyne 162, which underwent selective hydrogenation and desilylation to give (+)-parviflorin (153). In 1997, Trost’s

Synthesis of chiral cyclohexanes and carbasugars by 6-exo-dig radical cyclisation reactions

• Rajeev K. Shrivastava,
• Elise Maudru,
• Gurdial Singh,
• Richard H. Wightman and
• Keith M. Morgan

Beilstein J. Org. Chem. 2008, 4, No. 43, doi:10.3762/bjoc.4.43

• juncture we were able to separate the diastereoisomers, 3a (anti) and 3b (syn), by flash column chromatography on silica gel. Alternatively the syn isomer 3b could be prepared almost exclusively using D-ribonolactone as the starting material [23]. Desilylation of 3a was effective with TBAF in THF and

• 96% and 91% yields, respectively. These compounds were identical to those obtained from 2c after the diastereoisomers had been subjected to protection as MOM ethers on treatment with MOM chloride to give 5a and 5b followed by desilylation, the anti:syn ratio being 2.3:1. The syn-product was

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• unsuccessful, apparently because the silyl ether failed to survive the reaction conditions. Inelegant though it was, we were forced at this stage to change protecting groups on the alcohol. Fortunately, the drop in yield was not too serious when desilylation of 34 with aqueous hydrofluoric acid to give the