Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• -amicetose 7 [35]. To avoid the last step of the sequence, we envisaged a cross metathesis with acroleine, rather than methyl acrylate, to give enal 8 which should undergo spontaneous lactol formation after hydrogenation and desilylation. However, compared to cross metathesis reactions with methyl acrylate

• dealkoxylation of acetals [65] and for desilylation reactions of silyl ethers [66]. With in situ generated Pd/C (obtained from Pd(OAc)2 and charcoal according to Felpin’s protocol) [67] an improved selectivity was observed as the cleavage of the silyl groups could be suppressed. However, reductive dealkoxylation

• 83% combined yield (Table 3, entry 3). For the deprotection of 11 and 12 a desilylation initiated by TBAF, followed by acidic hydrolysis was investigated first. With isolated acetal 11, these conditions induced a scrambling of the benzoate and led to a mixture of the desired pyranose 16 and the

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

•  2) [24]. The use of 1.2 equiv of BF3·Et2O led to 9 in 84% isolated yield. Reduction of 9 with freshly prepared Raney nickel and subsequent desilylation afforded 10 over two steps in 73% yield. To introduce the desired E,E-diene present in 2 and 1, we realized that the procedure reported by

• components of Trichogramma turkestanica. Application of the iterative conjugate addition protocol for the preparation of 8. Deoxygenation and desilylation of 8. Vinylogous Horner–Wadsworth–Emmons olefination. Synthesis of α,β-unsaturated ester 15 using a Wittig reaction. Completion of the synthesis of the

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• . For example, Kubo and coworkers [47] showed that photoreactions of N-methyl-1,2- and 2,3-naphthalimides 8 and 12 with allylsilane 9 in MeCN can produce allylation products [48][49][50][51][52] that arise by a well-known sequence involving intermolecular SET, radical cation desilylation and radical

• delocalization arising by the orbital overlap, lowers the σC-Si bond dissociation energy and makes the silicon center more electropositive. Consequently, short-lived α-silyl cation radicals typically undergo fast, silophile-promoted desilylation to form the carbon centered free radicals 19 (Scheme 4). Based on

• the low oxidation potentials and known reactivity profile of cation radicals arising from α-trialkylsilyl substituted n-electron donors, it is feasible to design substrates that undergo sequential SET-desilylation processes to produce radicals or biradical intermediates in a highly regioselective and

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• bidentate chelation (Scheme 36). The substrate is bound anti to the bulky amino acid substituent (R) and reacts with the siloxyfuran via endo-type addition. Intramolecular silyl transfer, iPrOH mediated desilylation of the amide terminus, and protonation of the N–Ag bond delivers the final product and the

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• occurs to give TMSCl with regeneration of PPh3; meanwhile, the trapping of :CF2 by PPh3 gives the ylide. In Path B, a phosphonium salt 10, which is formed via a single-electron transfer (SET) mechanism, undergoes a chloride ion-promoted desilylation reaction to afford Ph3P=CF2 [42][43]. However, we could

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• both coupling partners 12 and 13 completely, by repeated evaporation of DCM solutions. Finally, a coupling yield of 68% was reached following the DEPC protocol. Desilylation (TBAF in THF/H2O) afforded 1 (HRESIMS found 755.49257, calcd. for C40H68NaN4O8 755.49294) in 12% yield after 10 steps from

• afforded building block 26. Coupling with Boc-protected dolaproine (27, DCC/DMAP/CSA) yielded ester 28 as a mixture of two diastereomers. After deprotection of the pyrrolidine, coupling with tripeptide 12 afforded O-silylated diazirinyl-substituted malevamide D (29, 68%). Desilylation (TBAF, THF/H2O 19:1

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• alcohol 18 and Mitsunobu reaction installed the required stereochemistry at C14. The free C14 hydroxy group was masked with protecting groups (MOM and TIPS) of different size and chemical nature to examine the face-selectivity of the [3,3]-sigmatropic rearrangement. After selective desilylation, alcohols

• aqueous CH2Cl2 to release triol 36, which was masked with different protecting groups (MOM, TBS, Piv). After desilylation, the liberated alcohols 40, 41 and 42 could be esterified with various cyclic and acyclic model A rings to give the targeted rearrangement precursors A (Scheme 6, Table 2). The

• , desilylation, oxidation and esterification (Scheme 14). Attempts to rearrange 93 under the optimized conditions were again unsuccessful. As expected, elimination of the OMOM group during the reaction was not detected due to the unfavoured orientation of the hydrogen and the leaving group. Subsequent acidic

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• diterpene 5-epi-vibsanin E (115), from the plant Viburnum awabuki (see Scheme 14) [104]. Starting from triene 108 cyclopropanation was achieved using vinyldiazo compound 101. The fomal [4 + 3]-cycloaddition proceeded through cis-divinylcyclopropane 109 to yield rearranged cycloheptadiene 110. Desilylation

• towards the total synthesis of salvileucalin B (292, see Scheme 35) isolated from the plant Salvia leucantha [213]. Starting from enantiopure trialkyne 282, desilylation was affected using TBAF, followed by ruthenium-catalyzed cycloisomerization [214] and cleavage of the chiral auxiliary to obtain

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• obtained as the by-product (Scheme 15, Table 6) [249]. The desilylation of the initially formed silicon peroxide followed by cyclization of the hydroperoxide accompanied by the attack on the electrophilic center is another example of the use of the Isayama–Mukaiyama reaction for the synthesis of cyclic

• peroxides. In some cases, the reaction with 1,5-dienes 46a–d produces, along with 1,2-dioxanes 51 (desilylation products of the corresponding 1,2-dioxanes 48), 1,2-dioxolanes (52b,d) as a result of cyclization of the corresponding peroxysilyl epoxides 49. In these reactions, unsaturated triethylsilyl

• activated double bond or a carbon atom of a keto or ester group). The desilylation of tert-butyldimethylsilylperoxy ketones 131a,b with HF followed by cyclization and subsequent reaction with monomethylethylene glycol afforded dioxolanes 132a,b in 75 and 88% yield, respectively. The intermediate

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• . Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial reduction and ester hydrolysis then gave resolvin D2 (1). Keywords: catalysis; eicosanoid; natural product

• bis-TES ether 15 and partial reduction of the alkyne using P2-Ni as catalyst [30] afforded the alkene 16. Desilylation of the primary TES group in 16 and concomitant oxidation to aldehyde 5 was achieved under Swern conditions as reported by Spur [31]. Deprotonation of salt 6 with LiHMDS followed by

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• the electron-deficient double bond, using polymethylhydrosiloxane (PMHS) [40] as a reducing agent and a BDP–Cu hydride catalyst. This variant of Stryker’s reagent [41] has more recently been described by Lipshutz et al. [42] and was found to furnish ketone 13 in 74% yield. Desilylation of 13 could be

• 19:1, it was converted to 26 via Mitsunobu inversion [55] with acetic acid as the nucleophile. The synthesis of stagonolide E commenced with the desilylation of 26 and Steglich esterification of the resulting allyl alcohol 27. One-flask reaction of 28 with catalyst B, followed by treatment with NaH

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess–Martin oxidation, the resulting keto-lactam 10 was subjected to a highly trans-stereoselective addition of the methylmagnesium iodide to give carbinol 11 as sole diastereomer. An efficient ring closure procedure

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• ether should be removed by using hydrolysis and fluoride-mediated desilylation, respectively. It was assumed that the multiple carbopalladation/cyclization sequence should give access to the fourfold-annulated ring system 13 in a single step. However, we knew that the domino process works much better in

• more promising candidates. But none of these domino products 13b–13f provided better results in a Tamao–Fleming reaction. When oxidizing reaction conditions were applied to silane 13b, only desilylation of the cyclic silyl ether occurred. Interestingly, benzylsilane 13c afforded the globally

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