Cerium(IV) sulfate tetrahydrate: a catalytic and highly chemoselective deprotection of THP,MOM, and BOM ethers

Tetrahydropyranyl (THP), methoxymethyl (MOM), and benzyloxymethyl (BOM) phenyl/alkyl ethers were efficiently cleaved to the corresponding parent hydroxyl compounds in good yields using catalytic amounts of Ce(SO₄)₂·4H₂O by microwave-assisted or conventional heating in methanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of THP ethers in the presence of triisopropylsilyl (TIPS) and tert-butyldiphenylsilyl (TBDPS) phenyl ethers.     

A mild and efficient selective tetrahydropyranylation of primary alcohols and deprotection of THP ethers of phenols and alcohols using PdCl2(CH3CN)2 as catalyst

Primary alcohols were selectively tetrahydropyranylated in good to excellent yields at room temperature using PdCl₂(CH₃CN)₂ as catalyst in tetrahydrofuran (THF) in the presence of phenols, secondary, and tertiary alcohols. The tetrahydropyranyl (THP) group could be efficiently removed using PdCl₂(CH₃CN)₂ as catalyst in CH₃CN, while other protection groups such as p-toluenesulfonyl (Ts), tert-butyldiphenylsilyl (TBDPS), benzyloxycarbonyl (Cbz), allyl, benzyl (Bn), and benzoyl (Bz) remained intact under these conditions.     

A mild and chemoselective method for the deprotection of tert-butyldimethylsilyl (TBDMS) ethers using iron(III) tosylate as a catalyst

The most common method for the deprotection of TBDMS ethers utilizes stoichiometric amounts of tetrabutylammonium fluoride, n-Bu₄N⁺F⁻ (TBAF), which is highly corrosive and toxic. We have developed a mild and chemoselective method for the deprotection of TBDMS, TES, and TIPS ethers using iron(III) tosylate as a catalyst. Phenolic TBDMS ethers, TBDPS ethers and the BOC group are not affected under these conditions. Iron(III) tosylate is an inexpensive, commercially available, and non-corrosive reagent.     

DDQ mediated regiospecific protection of primary alcohol and deprotection under neutral conditions: Application of new p-methoxy benzyl-pixyl ether as reagent of choice for nucleoside protection

A simple and efficient protocol is described for regiosepecific protection of primary hydroxyl group both in nucleosides and other molecules with p-methoxy-benzyl 2,7-dimethyl pixylether (MBDPE) in presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Furthermore, swift deprotection of 2, 7-dimethylpixyl (DMPx) is accomplished with DDQ in MeOH. Both procedures are successfully implemented on gram-scale synthesis of modified nucleosides. This protocol offers mild and neutral conditions for selective protection and deprotection of DMPx group while compatible in presence of other conventional protecting groups such as benzoyl, benzyl, THP, TBDPS and acetonide.     

Achievement of ring inversion of myo-inositol derivatives due to silyloxy/silyloxy repulsion enhanced by the trans-substituents on both sides

The introduction of quite bulky trialkyl or diarylalkylsilyl groups into vicinal trans-hydroxy groups induced a conformational flip of certain multifunctionalized cyclohexane rings from the usual chair form possessing more equatorial substituents (equatorial-rich chair form) into another chair-form that has more axial substituents (axial-rich chair form). This realization was experimentally revealed by the conformational study of the synthetic myo-inositol derivatives possessing two tert-butyldimethylsilyl (TBS), two triisopropylsilyl (TIPS), or two tert-butyldiphenylsilyl (TBDPS) groups on an adjacent trans-diol. Among them, the cyclohexane rings of the 4,5-bis-O-TIPS-myo-inositol, 4,5-bis-O-TBDPS-myo-inositol, and 1,2,3,6-tetra-O-benzyl-4,5-bis-O-TBDPS-myo-inositol were in the axial-rich chair form. Comparison of the ring conformations also revealed that the order of the repulsion was OTBDPS/OTBDPS>OTIPS/OTIPS>OTBS/OTBS, and the silyloxy/silyloxy repulsion was enhanced when the two silyloxy groups were placed in the center of the contiguous four equatorial substituents.     

Stereoselective glycosylation using the long-range effect of a [2-(4-phenylbenzyl)oxycarbonyl]benzoyl group

Highly α-selective glucosylation was effected by virtue of the solvent effect of cyclopentyl methyl ether and the long-range assistance of bulky 6-O-protective groups. Higher α-selectivity was obtained by the use of this solvent in comparison to conventional diethyl ether. α-Selectivity was further improved with the influence of 6-O-substituents, such as TBDPS and phthaloyl groups, the latter being mono esterified with a bulky alcohol.     

Simple Preparation Process of syn Phenylpropanolamines from Racemic O-TBDPS Cyanohydrins

In this article, a practically interesting route for the diastereoselective synthesis of phenylpropanolamines has been demonstrated for the first time. Using racemic O-tert-butyldiphenylsilyl (TBDPS) cyanohydrins as the starting materials, various syn phenylpropanolamines and derivatives (e.g., norpseudophedrine) have been successfully prepared in exellent diastereoselectivity via a practically interesting process.     

Tert-Butyldiphenylsilyl Derivatization for Liquid Chromatography and Mass Spectrometry

Abstract

Tert?butyldiphenylsilyl (TBDPS) derivatization has been investigated for the purposes of improving the HPLC analysis of polar compounds such as fatty acids, cholesterol and bile acids with ultraviolet absorption and/or mass spectral detection. Very mild reaction conditions (room temperature, 30 min) gave quantitative conversion of carboxyls and sterically accessible hydroxyls. The sterically hindered 7α and 12α hydroxyls of bile acids were not silylated to any extent under these conditions. The TBDPS ethers and esters proved stable under HPLC conditions and could be separated on an octylsilyl (RP-8) reverse phase column using acetonitrile as the mobile phase. Detection with an ultraviolet absorption detector at 254 nm was possible but 220 nm provided maximum sensitivity. The derivatives proved to be sufficiently volatile for electron-impact mass spectrometry and the apolar nature of the mobile phase facilitated combined LC/MS with a moving belt interface. The spectra were characterized by abundant ions at [M-57]⁺ due to loss of a tert?butyl radical and m/z 199 due to Ph₂SiOH⁺.     

Stereospecific N-oxide-mediated monoprotection of trans-3,4-dihydroxypyrrolidine derivatives

We found that the syntheses of O-monosubstituted 1-N-alkyl-trans-3,4-dihydroxypyrrolidines, normally faces serious obstacles due to poorly reactive hydroxy groups as a consequence of the presence of a highly basic pyrrolidine nitrogen atom, but that they can be obtained easily in high yields by conversion of 1-N-alkyl-trans-3,4-dihydroxypyrrolidines into the corresponding N-oxides. N-Oxidation leads to the loss of the pyrrolidine nitrogen atom basicity and discrimination in the reactivity of the originally equivalent hydroxy groups by at least one order of magnitude. The reaction of N-oxide derivatives with DMTrCl or TBDPSCl then proceeds in an almost quantitative yield, rapidly, and stereospecifically on the hydroxy group which is in a cis-position to the N-oxide oxygen atom. In contrast to the TBDPS derivative, the DMTr derivative could be easily deoxygenated with triphenylphosphine in high yield. The structures of the products obtained were confirmed by 2D NMR experiments, and quantum-chemical calculations were performed to explain the reaction mechanism of the stereospecific course of the reaction.     

A New Method for Selective Deprotection of Anomeric N,O-Dimethylhydroxylamine Promoted by TMSCl

TMSCl was shown to be an efficient reagent for selective deprotection of the anomeric position protected as N,O-dimethylhydroxylamine glycoside. This deprotection condition was proved to be compatible with a number of protecting groups, such as the TBDPS, acetyl, benzyl, benzylidene, and benzoyl groups.     

A Novel Chemoselective Cleavage of (tert‐Butyl)(dimethyl)silyl (TBS) Ethers Catalyzed by Ce(SO4)2⋅4 H2O

(tert‐Butyl)(dimethyl)silyl (^tBuMe₂Si; TBS) phenyl/alkyl ethers were efficiently cleaved to the corresponding parent hydroxy compounds in good yields using catalytic amounts of Ce(SO₄)₂?4 H₂O by microwave‐assisted or conventional heating in MeOH. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl (ⁱPr₃Si; TIPS) and (tert‐butyl)(diphenyl)silyl (^tBuPh₂Si; TBDPS) ethers.     

Divergent synthesis of cytotoxic styryl lactones isolated from Polyalthia crassa. The first total synthesis of crassalactone B

The first total synthesis of (+)-crassalactone B (2) and a new syntheses of (+)-crassalactone C (3) has been achieved starting from d-glucose. The natural products 2 and 3 can be selectively accessed by changing the conditions for TBDPS cleavage in the final intermediate 16. The synthesized natural products were evaluated for their cytotoxic activity against a panel of human tumour cell lines.     

Rapid,Acid‐Mediated Deprotection of Silyl Ethers Using Microwave Heating

Microwave heating of triethylsilyl (TES)‐ and tert‐butyldimethylsilyl (TBS)‐protected 1° and 2° alcohols in a mixture of equal parts acetic acid, tetrahydrofuran (THF), and water allows deprotection in as little as 5 min. tert‐butyldiphenylsilyl (TBDPS)‐ and triisopropylsilyl (TIPS)‐protected alcohols and silyl‐protected phenols are stable in these conditions. Thus, selective deprotection of TES‐ and TBS‐protected alcohols in the presence of TIPS or TBDPS ethers is possible. Similarly, alkyl silyl ethers can be deprotected in the presence of aryl silyl ethers.     

Selective cleavage of acetals with ZnBr2 in dichloromethane

A selective cleavage of acetals of 1,2- and 1,3-diols has been achieved under mild conditions using ZnBr₂ in dichloromethane at room temperature. Acetal types cleavable by this procedure include benzylidene, isopropylidene and cyclohexylidene acetals. This method is compatible with several other types of hydroxyl protecting groups such as Bn, Bz, TBDPS, TIPS and TBDMS.     

Action of Base on Methyl 6-Thio- (and 6-Deoxy-) 2-O-Methanesulfonyl-α-d-Glucopyranoside Derivatives1

Abstract

Treatment of methyl 4-O-benzoyl-3-O-tert-butyldiphenylsilyl-2-O-methanesulfonyl-6-thio-α-d-glucopyranoside (8) and its 6-deoxy analogue (11) with methanolic sodium methoxide, afforded methyl 2,3-anhydro-mannopyranoside derivatives as a consequence of an O₃ → O₄ TBDPS rearrangement. When the protecting group at C-3 was 2-methoxyethoxy methyl ether only deacylation and methanolysis of the methanesulfonyl group occurred.     

Facile route to 3,5-disubstituted morpholines: enantioselective synthesis of O-protected trans-3,5-bis(hydroxymethyl)morpholines

[reaction: see text] (3R,5R)-1 R1 & R2 = TBDPS, (3S,5R)-2 R1 = Bn,R2 = TBDPS, (3S,5S)-3 R2 & R2 = Bn. trans-3,5-Bis(benzyl/tert-butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)-symmetric class of chiral reagents, were prepared with excellent optical purity. A key step in the synthesis is the coupling of a serinol derivative with 2,3-O-isopropylideneglycerol triflate or its equivalent. This methodology was extended to the synthesis of chiral trans-3-(benzyloxymethyl)-5-(tert-butyldiphenylsilyloxymethyl)morpholine, a potentially useful chiral building block.     

Microwave-Assisted Protocols Applied to the Synthesis of 1′,2,3,3′,4,4′-Hexa-O-benzylsucrose

The sucrose derivative 1′,2,3,3′,4,4′-hexa-O-benzylsucrose is a key intermediate for the chemoselective synthesis of various useful materials, such as macrocycles, crown ether analogs, and polymers. Several strategies for the synthesis of this compound were explored by applying microwave-assisted protocols, thus permitting significant reductions of time and energy compared to other routes. The outcomes of the different approaches were compared and the optimal one, in terms of yield and reproducibility, was found to be the initial protection at the positions 6 and 6′, with tert-butyldiphenylsilylchloride (TBDPSCl) in the presence of 4-(dimethylamino)pyridine (4-DMAP) and pyridine as a solvent, then perbenzylation of the remaining hydroxyl groups, followed by selective deprotection of the TBDPS groups to obtain the title compound.     

Silyl group deprotection by Pd/C/H2. A facile and selective method

An easy, high yield, RT, short-reaction-time Pd/C hydrogenation of silyl groups is described. This includes TES, TPS, TBS, TBDMS, TIPS, and TBDPS. The relative selectivity of the process has been investigated and we can show, for example, that TES, TPS, TBS, and TBDMS removal can be performed in the presence of TIPS and TBDPS.     

Highly enantioselective oxidation of sulfides to sulfoxides by a new oxaziridinium salt

The new oxaziridinium salt 5 (R2 = TBDPS) is an effective reagent for the highly enantioselective oxidation of sulfides to sulfoxides with up to >99% ee and good yields. As such, it represents a new valuable nonmetallic alternative to the existing methods for asymmetric sulfoxidation.     

Solid-phase synthesis of oligonucleotide glycoconjugates bearing three different glycosyl groups: orthogonally protected bis(hydroxymethyl)-N,N'-bis(3-hydroxypropyl)malondiamide phosphoramidite as key building block

Diethyl O,O'-(methoxymethylene)bis(hydroxymethyl)malonate (3) was observed to undergo a stepwise aminolysis when treated with 3-aminopropanol. This allowed convenient preparation of bis(hydroxymethyl)-N,N'-bis(3-hydroxypropyl)malondiamide bearing orthogonal levulinyl (Lev) and tert-butyldiphenylsilyl (TBDPS) protections at the two N-hydroxypropyl groups (8). One of the hydroxylmethyl functions was then protected with a 4,4'-dimethoxytrityl (DMTr) group, and the other one was phosphitylated to obtain a methyl N,N-diisopropylphosphoramidite (1). This building block was used for the synthesis of oligonucleotide glycoconjugates (25 and 26) carrying three different sugar units. After conventional phosphoramidite chain assembly of the sequence containing 1, the 5'-terminal DMTr group was removed and an appropriate glycosyl 6-O-phosphoramidite was coupled. The remaining protections of the branching unit were removed in the order of Lev and TBDPS, and the exposed hydroxyl functions were reacted one after another with the desired glycosyl 6-O-phosphoramidites. Global deprotection and cleavage of the conjugate from the support were achieved by conventional ammonolysis.