A facile method for the rapid and selective deprotection of methoxymethyl (MOM) ethers

We describe a rapid and efficient method for selective deprotection of methoxymethyl (MOM) ethers using ZnBr₂ and n-PrSH, which completely removed MOM from diverse MOM ethers of primary, secondary, and tertiary alcohols or phenol derivatives. The deprotection takes less than ten minutes with both high yield and selectivity in the presence of other protecting groups. In addition, the rapid deprotection of MOM ethers of tertiary hydroxyls in high yield with no epimerization allows MOM to be a suitable protecting group for tertiary alcohols.     

Simple deprotection of acetal type protecting groups under neutral conditions

When acetals such as MOM ethers, MEM ethers, and THP ethers were heated in ethylene glycol or propylene glycol, solvolysis proceeded smoothly to produce alcohols in excellent yield. This reaction is a very promising method for chemoselective deprotection of acetal type protecting groups.     

Highly efficient deprotection of phenolic tetrahydropyranyl and methoxymethyl ethers and sequel cyclization to indanones using Sn(IV)Cl4 catalyst

Sn(IV)Cl₄ catalyst provided a rapid and efficient deprotection method for the phenolic THP and MOM ethers and sequel intramolecular Friedel–Crafts alkylation reaction of THP and MOM protected chalcone epoxides under mild conditions. The reaction took 2–3 min to give the products in excellent yield (90–98%) at 0 °C without affecting the other functional groups.     

Highly efficient and chemoselective cleavage of prenyl ethers using ZrCl4/NaBH4

An efficient and chemoselective deprotection of prenyl ethers of phenols and alcohols with ZrCl₄/NaBH₄ in DCM was achieved in high yields. The selectivity of prenyl ether deprotection is well demonstrated by carrying out the reaction in the presence of several other ether and ester functionalities.     

Reductive removal of methoxyacetyl protective group using sodium borohydride

Herein, we have developed a mild and selective reductive deprotection method for the MAc protected alcohols using sodium borohydride. The new deprotection conditions provide a complete orthogonality between O-MAc and other protecting groups such as tert-butyl ester, N-Boc, Fmoc, Cbz, O-TBDMS, N-benzyl, O-benzyl, O-acetyl, N-acetyl, N-MAc, etc. In addition to O-MAc deprotection, this method is also applicable for S-MAc deprotection.     

Synthesis and photoinduced deprotection of calixarene derivatives containing certain protective groups

Calixarene derivatives 1a , 1b , and 1c containing pendant tert‐butoxycarbonyl (t‐BOC) groups were synthesized in 81, 93, and 83% yields, respectively, by the reaction of C‐methylcalix[4]resorcinarene (CRA), p‐methylcalix[6]arene (MCA), and p‐tert‐butylcalix[8]arene (BCA) with di‐tert‐butyl dicarbonate using triethylamine as a base in pyridine. Calixarene derivatives 2a , 2b , and 2c containing pendant trimethylsilyl ether (TMSE) groups were obtained in 58, 50, and 82% yields, respectively, by the reaction of CRA, MCA, and BCA with 1,1,1,3,3,3‐hexamethyldisilazane using chlorotrimethylsilane as an accelerator in tetrahydrofuran. Calixarene derivatives 3a , 3b , and 3c containing pendant cyclohexenyl ether (CHE) groups were also prepared in 65, 78, and 84% yields, respectively, by the reaction of CRA, MCA, and BCA with 3‐bromocyclohexene using potassium hydroxide as a base as well as tetrabutylammonium bromide as a phase‐transfer catalyst in N‐methyl‐2‐pyrolidone. The photoinduced deprotection of calixarene derivatives 1a – c was examined with bis‐[4‐(diphenylsulfonio)phenyl]sulfide bis(hexafluorophosphate) as a photoacid generator on UV irradiation followed by heating in the film state, and it was found that the deprotection of the t‐BOC groups of 1a proceeded smoothly in high conversion. The deprotection rates of the t‐BOC groups of 1b and 1c were much lower than that of 1a under the same irradiation conditions. The photoinduced deprotection of calixarenes 2b – c containing tetramethylsilane groups as well as 3a – c containing CHE groups were also examined under similar reaction conditions in the film state, and it was found that the deprotection rates of calixarenes 2b – c and 3a – c were lower than those of the corresponding 1a – c calixarenes. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1481–1494, 2001     

A highly efficient, mild, and selective cleavage of beta-methoxyethoxymethyl (MEM) ethers by cerium(III) chloride in acetonitrile

[structure: see text]. A highly selective cleavage of MEM ethers has been achieved in high yields using CeCl3.7H2O in refluxing acetonitrile under mild and neutral reaction conditions. The method is very rapid and compatible with other hydroxyl protecting groups such as Bn, TBDPS, Ac, Me, Tr, PMB, benzylidene, THP, MOM, BOM, and NHAc present in the substrate.     

A mild, efficient and selective deprotection of t-butyldimethylsilyl-protected phenols using cesium carbonate

A mild and efficient method for the deprotection of aryl t-butyldimethysilyl (TBS) ethers is described. The protecting group TBS could be cleaved from aryl silyl ethers using cesium carbonate in DMF-H₂O at room temperature to give the corresponding phenols in excellent yields. The reaction conditions allowed selective deprotection of aryl TBS-protected phenols in the presence of TBS, phenyloxycarbonyl or tetrahydropyranyl-protected alcohols.     

Vanadium Hydrogen Sulfate (I): Chemoselective Trimethylsilylation of Alcohols and Deprotection of Trimethylsilyl Ethers

Trimethylsilylation of alcohols with hexamethyldisilazane (HMDS) catalyzed by V(HSO₄)₃ under mild and completely heterogeneous reaction condition is reported. The method is highly chemoselective for the protection of alcohols in the presence of phenols, amines and thiols. Also, the deprotection of trimethylsilyl ethers is performed in the presence of V(HSO₄)₃ at room temperature in good to high yields.     

An efficient protocol for the preparation of MOM ethers and their deprotection using zirconium(IV) chloride

An efficient protocol for the preparation of MOM ethers from alcohols and formaldehyde dimethyl acetal (DMFA) using ZrCl₄ (10 mol %) at room temperature under solvent free conditions has been developed. Similarly, the same Lewis acid, ZrCl₄ (50 mol %), in isopropanol at reflux was utilised for the deprotection of MOM ethers.     

12-Tungstophosphoric acid supported on inorganic oxides as heterogeneous and reusable catalysts for the selective preparation of alkoxymethyl ethers and their deprotections under different reaction conditions

A wide variety of primary and secondary alcohols were efficiently converted to their corresponding methoxymethyl (MOM) and ethoxymethyl (EOM) ethers in the presence of catalytic amounts of supported H₃PW₁₂O₄₀ on silica gel and zirconia at room temperature and under microwave irradiation at solvent-free conditions, whereas, phenols and tertiary alcohols remained intact under the same reaction conditions. Deprotection of these ethers to their parent alcohols was also achieved using these heterogeneous catalysts in ethanol, as a green solvent, under reflux conditions and microwave irradiation. Selective deprotection of primary and secondary MOM- and EOM-ethers in the presence of phenolic and tertiary ones, methyl and benzyl ethers, esters and trimethylsilyl ethers was achieved by these reagent systems. The present methodology offers several advantages such as short reaction times, high yields, simple procedure, heterogeneous reaction conditions, selectivity, non-toxicity and reusability of the catalysts.     

A simple and selective method for the O-AcCl removal using sodium borohydride

A deprotection of chloroacetylated alcohols using NaBH₄ is reported. The free alcohols are obtained in excellent yields. The reaction was performed on primary, secondary, alkyl, allyl, benzylic alcohols and phenols. The compatibility of the method with other sensitive or protective groups is demonstrated.     

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.     

Perfluoroalkylsulfonyl fluoride-mediated abnormal Beckmann rearrangement of steroid 17-oximes with acid-labile groups

A perfluoroalkylsulfonyl fluoride-mediated abnormal Beckmann rearrangement is reported which transforms steroid 17-oximes to the corresponding alkene nitriles regioselectively in good yields. This reaction is rapid (completes in 25 min), mild (proceeds at room temperature) and, most importantly, tolerates various acid-labile functional groups, such as methoxymethyl (MOM), ketal, and methyl enol ether, providing access to molecules that would be difficult to synthesize using existing methods.     

A Green,Solvent‐Free,Microwave‐Assisted,High‐Yielding YbCl3 Catalyzed Deprotection of THP/MOM/Ac/Ts Ethers of Chalcone Epoxide and 2′‐Aminochalcone and Their Sequel Cyclization

Under microwave and solvent‐free conditions, YbCl₃ efficiently catalyzed the deprotection of tetrahydropyran‐2‐yl, methoxymethyl (MOM), acetyl, and tosyl groups and sequel cyclization of chalcone epoxide to 2‐hydroxyindanone and 2′‐aminochalcone to aza‐flavanone. The reaction afforded the products in excellent yield (78–99%) at 850 W microwave heating within 1–5 min under eco‐friendly conditions. The merits of the presented protocol include high yield, use of microwave irradiation, solvent‐free condition, catalyst reusability, and no need for purification with column chromatography. The present method is very much milder but more advanced than those reported earlier.     

CBr4-photoirradiation protocol for chemoselective deprotection of acid labile primary hydroxyl protecting groups

CBr₄-photoirradiation protocol was found to be a mild, highly efficient and selective method for deprotection of isopropylidene, benzylidene, triphenylmethyl and tert-butyldimethylsilyl protecting groups on sugar molecules. The conditions of this reaction can also be used to cleave peptides off from acid-labile resin linkers in solid-phase peptide synthesis.     

A Mild and Versatile Method for the Tetrahydropyranylation of Alcohols and Their Detetrahydropyranylation

An efficient and mild method for tetrahydropyranylation of alcohols and their detetrahydropranylation using NH₄Cl is described. This protocol provides a useful alternative tetrahydropyranylation of alcohols and their deprotection at different pH.

     

Microwave-assisted rapid and efficient deprotection and direct esterification and silylation of MOM and EOM ethers catalyzed by [Hmim][HSO4] as a Br?nsted acidic ionic liquid

Abstract  

1-Methylimidazolium hydrogensulfate, [Hmim][HSO₄], a Br?nsted acidic room temperature ionic liquid, is used as a catalyst and reaction medium for facile and eco-friendly deprotection of methoxymethyl (MOM) and ethoxymethyl (EOM) ethers to their corresponding alcohols under thermal conditions (Δ) and microwave irradiation (MW). Furthermore, one-pot interconversion to the respective acetates and trimethylsilyl (TMS) ethers was also achieved.     

Enzymatic Resolution of O‐(Methoxymethyl)‐Protected Tropane‐diols

A convenient synthetic route to enantiomerically pure tropane‐diol building blocks is described. The reaction sequence started from tropenone derivatives 1 , which were dihydroxylated to give 6,7‐dihydroxytropanone derivatives 2 . After introduction of the methoxymethyl (MOM) protecting group in diol 2a , a lipase‐mediated resolution of the resulting racemic mono‐MOM ether (±)‐ 5d with vinyl acetate and vinyl trifluoroacetate gave the acetates (?)‐ 6d and (?)‐ 6f , respectively, with 96–99% ee, and MOM ether (+)‐ 5d with up to 89% ee. Deacetylation of (?)‐ 6d afforded quantitatively MOM ether (?)‐ 5d with 99% ee, the absolute configuration of which was assigned via the modified Mosher method to be (R) at C(6). Enzymatic treatment of unprotected diol 2a with vinyl trifluoroacetate or alkoxycarbonylation resulted in the formation of C_s‐symmetrical products 9 and 12 rather than the desired desymmetrized derivatives.     

A new method for the stereoselective construction of angular methyl group of fuzed cyclic ethers

A convenient method for the stereoselective construction of angular methyl group of fuzed cyclic ethers is described. Reactions of mixed thioacetals with Me₂Zn/Zn(OTf)₂ afforded the corresponding methylated products in good yields. Various protective groups such as MOM ether, benzylidene acetal, TBS ether, and pivaloyl group were stable under the reaction conditions.