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.     

Synthesis of 3,4,5-trisubstituted indoles via iterative directed lithiation of 1-(triisopropylsilyl)gramines

Directed lithiation of 1-(triisopropylsilyl)gramines 1 with tert-butyllithium followed by reaction with trimethylsilylmethyl azide produced 4-amino-1-(triisopropylsilyl)gramines 7. The N-tert-butoxycarbonyl derivatives 8 were lithiated selectively at C-5 with tert-butyllithium and the lithiated species were reacted with a variety of electrophiles to give 5-functionalized compounds, 9 and 10. A facile method to produce 3,4,5-trisubstituted indoles from readily available gramine derivatives is thereby established.     

A direct transformation of O-silyl groups into O-trichloroacetates. A novel synthetic approach to protein kinase C ligands: 1-oleoyl-2-acetyl- and 1-hexadecyl-2-acetyl-sn-glycerols

A fluoride ion-promoted direct esterification of tert-butyldimethylsilyl- (TBDMS), or triisopropylsilyl (TIPS)-protected glycerol derivatives by means of trichloroacetic anhydride (TCAA), followed by removal of the trichloroacetyl transient protection, provides a new, efficient entry to stereochemically pure 1-oleoyl-2-acetyl- and 1-O-hexadecyl-2-acetyl-sn-glycerols.     

Aluminium Chloride Hexahydrate (AlCl3 · 6H2O): An Efficient,Facile, Mild,And Highly Chemoselective Catalytic Deprotection of Tert-Butyldimethylsilyl (TBS) Ethers

tert-Butyldimethylsilyl (TBS) phenyl / alkyl ethers were cleaved to the corresponding efficiently parent hydroxyl compounds in good yields using catalytic amounts of AlCl₃ · 6H₂O by conventional or microwave-assisted heating in methanol or isopropanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl and tert-butyldiphenylsilyl ethers.     

Four-component one-pot synthesis of a branched manno-pentasaccharide: tert-butyldiphenylsilyl ether as an in situ removable carbohydrate-protecting group

A branched mannose-pentasaccharide was synthesized in a convergent one-pot sequence involving chemo- and regioselective glycosylations of suitable acceptors and in situ removal of tert-butyldiphenylsilyl group. The process demonstrated that a combination of TMSOTf and TfOH can be used as an effective reagent for the fast and selective in situ de-protection of tert-butyldiphenylsilyl group, and also serve as part of the promoter system for the subsequent glycosylation reaction.     

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 new entry to carbocycles: synthesis of cyclopentene and cyclohexene derivatives through endo-mode ring closure of allenyl sulfones

Treatment of dimethyl 4-(phenylsulfonyl)-4,5-hexadiene-1,1-dicarboxylate with potassium tert-butoxide in tert-butanol at room temperature effected successive endo-mode ring closure at the sp-hybridized carbon center and demethoxycarbonylation of the resulting malonate derivative leading to the exclusive formation of methyl 2-methyl-3-(phenylsulfonyl)-1-cyclopentenecarboxylate. An additional seven allenyl sulfones having a 1,3-dicarbonyl functionality gave the corresponding cyclopentene or cyclohexene derivatives in high yields.     

Ring conformations of d-glucose derivatives possessing two bulky silyl protecting groups at the 3,4-positions; the first observation of a stable full-axial chair conformer without bridge structures

The ring conformations of 3,4-bis-O-tert-butyldimethylsilyl- and 3,4-bis-O-tert-butyldiphenylsilyl-d-glucopyranoses as well as the corresponding phenyl 1-thio-d-glucopyranosides were investigated. Observations showed that the introduction of the two tert-butyldiphenylsilyl groups can flip the pyranose-ring into the ¹C₄ conformation possessing more axial substituents. All the substituents of the 3,4-bis-O-tert-butyldiphenylsilyl-β-d-glucopyranose were axially oriented.     

Stereoselective preparation of trisubstituted (Z)-alkenes; synthesis of the C17-C27 fragment of (−)-laulimalide

A Ni-catalyzed cross-coupling reaction of (Z)-5-(tert-butyldiphenylsilyl)oxy-3-bromo-1-trimethylsilyl-3-penten-1-yne (1) with alkyl Grignard reagent gives (Z)-3-alkyl-5-(tert-butyldiphenylsilyl)oxy-1-trimethylsilyl-3-penten-1-ynes (2) stereospecifically in good yields. The (Z)-enyne 2a is transformed in four steps to (Z)-3-methyl-5-silyloxy-3-pentenal (3), which is coupled with ketophosphonate 4 to give enone 13. The η-hydroxyallyl methanesulfonate derived from 13 is cyclized to 3,6-dihydro[2H]pyran by an intramolecular SN2′ reaction stereoselectively, furnishing a C17-C27 carbon unit of (−)-laulimalide.     

Effective chemoselective deprotection of 3,4-dimethoxybenzyl (DMB) ethers in the presence of benzyl and p-methoxybenzyl (PMB) ethers by phenyliodine(III) bis(trifluoroacetate) (PIFA)

In this Letter, a selective deprotection of the alcohol protecting 3,4-dimethoxybenzyl (^3,4DMB) group is described. The hypervalent iodine(III) reagent phenyliodine bis(trifluoroacetate) (PIFA) is found to be an efficient reagent for the chemoselective deprotection of ^3,4DMB ethers in the presence of benzyl, p-methoxybenzyl, methoxymethyl, tert-butyldimethylsilyl, and tert-butyldiphenylsilyl ethers under mild conditions. This is the first example of the selective deprotection of the ^3,4DMB group from a hydroxy group with PIFA.     

One-pot tethering of organic molecules through non-symmetric malonate derivatives

A new method for one-pot chemoselective heterobifunctional cross-linking of organic molecules is described. The method is based on tert-butyldiphenylsilyl malonate and involves two sequential carbodiimide couplings with two different molecules possessing a hydroxy or an amino functionality with one intermediate one-pot fluoride deprotection.     

Optimization of Grignard ring-opening of α-brominated dioxolanes for the preparation of β-hydroxy-protected vinyl ethers by a three-step one-pot procedure

Aliphatic, cyclic, and aromatic benzoate-protected γ-hydroxy enol ethers were prepared from α-brominated dioxolanes by a three-step reaction procedure and a one-pot protocol involving Grignard reagent formation, ring-opening, and final benzoate protection. Additionally, tert-butyldiphenylsilyl, acetate, and 4,4′-dimethoxytrityl were also successfully used as alternative protecting groups.     

Asymmetric Michael addition of malonates to enones catalyzed by a siloxy amino acid lithium salt

Siloxy amino acid lithium salt, O-tert-butyldiphenylsilyl l-serine lithium salt, was found to be an effective catalyst for the asymmetric Michael addition reaction of malonates to enones.     

Interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines—a pathway to new sterically hindered N,N-disubstituted o-aminophenols

The interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines has been studied. The synthetic procedure was developed in order to synthesize a series of new N,N-disubstituted o-aminophenols. The interaction of 3,5-di-tert-butyl-o-benzoquinone with dimethylamine leads to 2-(N,N-dimethylamino)-4,6-di-tert-butyl-phenol, which is oxidized in the reaction medium by the parent 3,5-di-tert-butyl-o-benzoquinone forming spirocompound 4,5′,6,7′-tetra-tert-butyl-3′-methyl-3′H-spiro[1,3-benzodioxol-2,2′-[1,3]benzoxazole].     

Reaction of tert-butyl isocyanide and dialkyl acetylenedicarboxylates in the presence of 2-acetylbutyrolactone. Synthesis of functionalized α-methylene-γ-butyrolactones

Reaction of tert-butyl isocyanide with dialkyl acetylenedicarboxylates in the presence of 2-acetylbutyrolactone leads to the formation of dialkyl (E)-2-{(tert-butylamino)[2-oxo-4,5-dihydro-3(2H)-furanylidene]methyl}-2-butenedioates.     

Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature

Commercially available copper(II) tetrafluoroborate hydrate was found to be a highly efficient catalyst for chemoselective N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions and at room temperature. Various aromatic amines were protected as their N-tert-butyl carbamates in high yields and in short times. No competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation was observed. Chemoselective N-tert-butoxycarbonylation was achieved with substrates bearing OH and SH groups. Chiral α-amino acid esters afforded the corresponding N-t-Boc derivatives in excellent yields.     

Asymmetric synthesis of trans-4,5-dioxygenated cyclopentenone derivatives by organocatalyzed rearrangement of pyranones and enzymatic dynamic kinetic resolution

Dioxygenated cyclopentenones are versatile building blocks for the synthesis of several natural products. Herein we report a direct asymmetric synthesis of trans-4,5-dioxygenated cyclopentenone derivatives through base-catalyzed rearrangement of pyranones followed by dynamic kinetic resolution. Milder conditions than previously reported for this rearrangement have been found regarding amine base catalysis, solvent and temperature effects. All data supports a mechanism involving cyclization of an intermediate formed by electrocyclic ring opening of a pyranone-derived enol. We have developed conditions for asymmetric synthesis of trans-4-tert-butoxy-5-hydroxycyclopent-2-enone, in 81% yield and 95% ee, and analogous dioxygenated cyclopentenones, via a lipase induced dynamic kinetic resolution.     

Supramolecular self-assemblies of stereoisomers of p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim with some metal cations

Novel p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim in cone, partial cone and 1,3-alternate conformations were synthesized and their receptor properties toward metal ions of p- (Al³⁺, Pb²⁺) and d- (Fe³⁺, Co³⁺, Ni²⁺, Cu²⁺, Ag⁺, Cd²⁺) elements were investigated by picrate extraction and dynamic light scattering (DLS). It was shown that the p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups are effective extractants of soft metal cations. The complex stoichiometry depended on the receptor configuration. All the p-tert-butyl thiacalix[4]arene derivatives with hydrazide fragments were able to form nanoscale aggregates but did not show self-association abilities.     

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.     

Synthesis of derivatives of pyrido[3′,2′:4,5]furo[3,2-c]isoquinoline heterocyclic system

An approach to the synthesis of derivatives of new heterocyclic system, pyrido[3′,2′:4,5]-furo[3,2-c]isoquinoline, was suggested. A condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation product with potassium tert-butoxide leads to substituted pyrido[3′,2′:4,5]furo[3,2-c]-isoquinolin-5(6H)-ones. Similarly, a condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with 2-(chloromethyl)benzonitrile and subsequent treatment of the condensation product with potassium tert-butoxide gives substituted 5-aminopyrido[3′,2′:4,5]furo[3,2-c]-isoquinolines.