Bistrimethylsilylpropargylic Ether:  A Versatile Ambident Synthon to Access Substituted Allenyne Ethers and α-Substituted Bispropargylic Alcohols

Brossat, Maude; Heck, Marie‐Pierre; Mioskowski, Charles

doi:10.1021/jo0709753

Cited by 21 publications

(6 citation statements)

References 26 publications

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“…Changing the base for NaHCO 3 slowed down the transformation and allowed identification of the unstable ynone 12 (obtained selectively as a1 .2:1 mixture with the expected carbinol 11 c), likely resulting from ab ase-induced isomerization in allendiyne ester [20] followed by the terminal addition of am olecule of MeOH. In contrastt ot he DAC 2-Ac, the BAC 11 c-Ac turned out to be highly sensitivet os tandard saponification conditions.…”

Section: Scheme6enantioselective Synthesiso Fbacs (R)-(à)-and (S)-(+mentioning

confidence: 99%

“…Exposure to one equivalent of K 2 CO 3 in MeOH led to rapid decomposition( Scheme9). Changing the base for NaHCO 3 slowed down the transformation and allowed identification of the unstable ynone 12 (obtained selectively as a1 .2:1 mixture with the expected carbinol 11 c), likely resulting from ab ase-induced isomerization in allendiyne ester [20] followed by the terminal addition of am olecule of MeOH. Other hydrolysis conditions proved to be nonproductive (MeCN/NH 4 OH, Et 2 O/dilute aq.…”

Section: Compoundmentioning

confidence: 99%

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Skeletal Optimization of Cytotoxic Lipidic Dialkynylcarbinols

et al. 2018

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In line with a recent study of the pharmacological potential of bioinspired synthetic acetylenic lipids, after identification of the terminal dialkynylcarbinol (DAC) and butadiynyl alkynylcarbinol (BAC) moieties as functional antitumor pharmacophoric units, this work specifically addresses the issue of carbon backbone length. A systematic variation of the aliphatic chain length was thus carried out in both the DAC and BAC series. The critical impact of the length of the lipidic skeleton was first confirmed in the racemic series, with the highest cytotoxic activity observed for C to C backbones. Enantiomerically enriched samples were prepared by asymmetric synthesis of the optimal C DAC and C BAC derivatives. Samples with upgraded enantiomeric purity were alternatively produced by enzymatic kinetic resolution. Eutomers possessing the S configuration displayed cytotoxicity IC values as low as 15 nm against HCT116 cancer cells, the highest level of activity reached to date in this series.

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Section: Scheme6enantioselective Synthesiso Fbacs (R)-(à)-and (S)-(+mentioning

confidence: 99%

Section: Compoundmentioning

confidence: 99%

Skeletal Optimization of Cytotoxic Lipidic Dialkynylcarbinols

et al. 2018

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“…Table 1 The chemistry of DACs, mostly tertiary, is largely documented for their use as basic synthons in the synthesis of hexaoxy- [6]pericyclynes serving as direct precursors of carbo-benzenes [8,9] or related acetylenic chromophores [10]. In the secondary DAC series, trimethylsilyl-penta-1,4-diyn-3-ol 3a is a currently referenced dissymmetrical equivalent of diethynylmethanol (Scheme 2) [9,11]. …”

Section: Resultsmentioning

confidence: 99%

On terminal alkynylcarbinols and derivatization thereof

et al. 2015

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Abstract. The chemistry of three prototypes of secondary alkynylcarbinols (ACs), recently highlighted as challenging targets in anti-tumoral medicinal chemistry, is further documented by results on n-alkyl, alkynyl and alkenyl representatives. The N-naphthyl carbamate of an n-butyl-AC is thus characterized by X-ray crystallography. A novel dialkynylcarbinol (DAC) with synthetic potential is described, namely the highly dissymmetrical triisopropylsilyl-protected version of diethynylmethanol. The latter is shown to act as a dipolarophile in a selective Huisgen reaction with benzyl azide under CuAAC click conditions, giving an alkenyl-AC, where the alkene unsaturation is embedded in a 1,4-disubstituted 1,2,3-triazole ring, as confirmed by X-ray crystallography. ________________________________________________________________________________

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“…[1][2][3][4][5][6][7][8] Also, THP-protected alcohols are generally stable under a wide range of reaction conditions and reagents, such as metal hydrides, alkyllithiums, Grignard reagents, and catalytic hydrogenation. [9][10][11][12][13] For the THP ethers, a number of deprotecting methods have been introduced. 14) Various acids, including AcOH, 15) pyridinium para-toluenesulfonate (PPTS), 1) boric acid, 16) and TsOH, 17) can cleave THP ethers to regenerate free alcohols with high efficacy.…”

Section: Notesmentioning

confidence: 99%

One-Step Transformation of Tetrahydropyranyl Ethers Using Indium(III) Triflate as the Catalyst

Mineno

Nikaido

Kansui

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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NotesTetrahydropyranyl (THP) group is a well-utilized moiety, mainly as a tool to protect alcohol units due to its feasibility of installation and low cost. Stirring the free alcohols with 3,4-dihydro-2H-pyran (DHP) under acidic conditions can easily produce THP-protected alcohols.1-8) Also, THP-protected alcohols are generally stable under a wide range of reaction conditions and reagents, such as metal hydrides, alkyllithiums, Grignard reagents, and catalytic hydrogenation. O, 19,20) and CuSO 4 · 5H 2 O, 21) has also been reported.Previously, we have reported a couple of convenient reaction methods using indium or indium-related reagents. [22][23][24][25] The authors have recently developed a practical approach to tetrahydropyranylation and depyranylation of various alcohols using indium(III) triflate.26) It is worth noting that with the same catalyst, the reactions proceed in directions of both protection and deprotection. In the presence of a catalytic amount of indium(III) triflate, protection of alcohols is carried out using CH 2 Cl 2 as the solvent, whereas deprotection uses MeOH/H 2 O as the solvent. Kamal et al. also reported that tetrahydropyranylation can be controlled using catalytic aluminum(III) triflate. 27) Another report has shown the cleavage of THP ethers using titanium(III) triflate in good yields.28) According to our earlier experiments, indium(III) triflate was revealed to be an efficient catalyst for the transformation of THP ethers into their corresponding acetates. In further intensive work, we have developed a useful transforming reaction of THP ethers using various anhydride moieties with indium(III) triflate as the catalyst. Herein, we report the details of this one-step transformation. Results and DiscussionTHP-protected benzyl alcohol and N-(2-hydroxyethyl)-phthalimide were used as the starting materials. First, the suitability of the catalysts was examined by reactions with acetic anhydride (Chart 1). In both cases, the reaction proceeded and produced excellent yields in a shorter time when indium(III) triflate was employed as the catalyst (Table 1, entries 1 and 3), as compared with indium(III) chloride (Table 1, entries 2 and 4). Giving the satisfactory results with indium(III) triflate, we then expanded our investigation to the other types of anhydrides. The reactions were carried out with THP-protected benzyl alcohol, N-(2-hydroxyethyl)phthalimide, and a wide range of anhydrides (Chart 2).As expected, the reactions with another aliphatic anhydride of isobutyric anhydride generated similar satisfactory results (Table 2, entries 1 and 7). In the case of benzoic anhydride, the reaction required an extended period of time, although acceptable results were obtained (Table 2, entries 2 and 8). With the exception of entry 5, these conditions were then applied to the cyclic anhydrides, and the reactions produced entirely poor yields. These results were presumably due to the low reaction temperature. When reactions were resumed at reflux using THF as the solvent, good to excellent out...

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Bistrimethylsilylpropargylic Ether: A Versatile Ambident Synthon to Access Substituted Allenyne Ethers and α-Substituted Bispropargylic Alcohols

Cited by 21 publications

References 26 publications

Skeletal Optimization of Cytotoxic Lipidic Dialkynylcarbinols

Skeletal Optimization of Cytotoxic Lipidic Dialkynylcarbinols

On terminal alkynylcarbinols and derivatization thereof

One-Step Transformation of Tetrahydropyranyl Ethers Using Indium(III) Triflate as the Catalyst

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