Synthesis and use of chiral substituted benzenes containing 1,2-diols protected as cyclic acetals

1,2-Dihydroxy benzenes have been protected as cyclic diacetals using 2,3-butane dione. These diacetals are extremely robust and can be further chemically diversified and resolved with chirality embedded in the 1,4-dioxane ring attached to the aromatic back bone as a result of the anomeric effect. These systems can serve as ligands, auxiliaries or organocatalysts for asymmetric synthesis.     

4-(tert-Butyldimethylsilyloxy)benzylidene acetal: a novel benzylidene-type protecting group for 1,2-diols

A novel 1,2-diol-protecting group, p-silyloxybenzylidene group, has been developed. In addition to the stepwise deprotection conditions including desilylation and the subsequent acidic hydrolysis of the p-hydroxybenzylidene group in AcOH-THF-H₂O, we have established the one-pot deprotection under basic conditions [K₂CO₃ (5 equiv), NH₂OH·HCl (5 equiv), and CsF (1 equiv) in MeOH-H₂O].     

Dielectric relaxation studies of monoalcohol solutions with 1,2-diols

Dielectric relaxation processes in solutions of monoalcohols with ethanediol, 1,2-propanediol, and 1,2-butanediol have been studied using the dielectric time domain spectroscopy technique. The dielectric spectrum has been analyzed in terms of two dispersions. The influence of varying content of diol, and of chainlength of the alcohol, on the static dielectric constant _s and on the main dispersion is reported. For the long-chain alcohols _s is lowered and the main relaxation time successively shortened with the addition of diol to the solution. The results are compared to these found for aqueous alcohol solutions and discussed in terms of a structural model with rupturing of predominantly linear complexes on addition of water, diols, or on increasing the temperature.     

Enzymatic removal of carboxyl protecting groups. 1. Cleavage of the tert-butyl moiety

[reaction: see text] A recent discovery that a certain amino acid motif (GGG(A)X-motif) in lipases and esterases determines their activity toward tertiary alcohols prompted us to investigate the use of these biocatalysts in the mild and selective removal of tert-butyl protecting groups in amino acid derivatives and related compounds. An esterase from Bacillus subtilis (BsubpNBE) and lipase A from Candida antarctica (CAL-A) were identified as the most active enzymes, which hydrolyzed a range of tert-butyl esters of protected amino acids (e.g., Boc-Tyr-O(t)Bu, Z-GABA-O(t)Bu, Fmoc-GABA-O(t)Bu) in good to high yields and left Boc, Z, and Fmoc-protecting groups intact.     

Syntheses of new C2-symmetric,optically active 1,2-diols bearing tertiary alkyl groups

New C₂-symmetric chiral 1,2-diols, 1,2-bis(1-adamantyl)-1,2-ethanediol and 3,3,6,6-tetramethyl-1,2-cyclohexanediol, were synthesized by the use of a new resolution method.     

Photolabile protection of 1,2- and 1,3-diols with salicylaldehyde derivatives

1,2- and 1,3-diols, including carbohydrates, can be readily caged as acetals of 5-methoxy- or 5-hydroxysalicylaldehydes. Irradiation of these acetals with 300 nm light results in their efficient (Phi = 0.2-0.3) cleavage, regenerating an aldehyde and a glycol in excellent chemical yield. Photoreactive 5-hydroxysalicylaldehyde acetals can be produced by mild in situ reduction of photostable p-quinone precursors.     

New protecting groups in the synthesis of oligosaccharides

The review is focused on new hydroxy and amino protecting groups in carbohydrate chemistry developed or gained popularity over the last 15 years. Representative examples for the protecting group manipulations are given.     

Enzymatic removal of carboxyl protecting groups. 2. Cleavage of the benzyl and methyl moieties

[reaction: see text] Enzymes are versatile reagents for the efficient removal of methyl and benzyl protecting groups. An esterase from Bacillus subtilis (BS2) and a lipase from Candida antarctica (CAL-A) allow a mild and selective removal of these moieties in high yields without affecting other functional groups.     

Convenient synthesis of optically active deuterated primary alcohols via deuteride reduction of acetals derived from homochiral (1R1,2R1)-3,3,3-trifluoro-1-phenylpropane-1,2-diols

(1R)-1-Deuterated alcohols with high enantiomeric excess were prepared via TiCl₄/Et₃SiD reduction of acetals arising from the reaction of aldehydes with (1S,2S)-3,3,3-trifluoro-1-phenylpropane-1,2-diol 9. Such a chiral auxiliary was synthesized in an enantiomerically pure form starting from l-mandelic acid. Due to its benzylic nature, it was easily removed from the reaction product of the reductive 1,3-dioxolane ring-cleavage to afford the desired α-deuterated alcohol.     

Cleavage of alkoxycarbonyl protecting groups from carbamates by t-BuNH2

An efficient, simple protocol for the selective cleavage of a variety of N-alkoxycarbonyl protecting groups by t-BuNH₂/MeOH is described. The scope of the procedure was explored for a series of indole, aniline and pyrrolidine carbamate derivatives containing other potentially reactive functional groups affording a clean cleavage of the carbamate group.     

Fluorous dimethylthiocarbamate (DMTC) protecting groups for alcohols

N,N-Bis(perfluoroalkyl)thiocarbamoyl chlorides (^FDMTC-Cls) were synthesized as reagent for the protection of alcohols. Using the crystalline ^FDMTC-Cls, the ^FDMTC groups were introduced into the alcohol molecules in excellent yields in the presence of sodium hydride in THF at room temperature. The products were separated from the excess alcohols by solid-phase extraction with a fluorous reverse-phase silica gel column (Fluorous Solid Phase Extraction; FSPE). The ^FDMTC groups were readily removed by oxidation with m-chloroperbenzoic acid (m-CPBA) and subsequent hydrolysis with KHCO₃.     

(Triisopropylsilyl)acetaldehyde acetal as a novel protective group for 1,2-diols

(Triisopropylsilyl)acetaldehyde dimethyl acetal (TIPS-ADMA) was synthesized from chlorotriisopropylsilane in three steps. Cyclic and acyclic 1,2-diols can be transformed to (triisopropylsilyl)ethylidene acetals (TIPS-AA). Removal of the acetal by LiBF₄ regenerates the starting diol in excellent yield even in the presence of an acetonide of 1,2-diol. The TIPS-AA group can survive under the deprotection conditions of the acetonide in acetic acid at 80 °C. Selective protection of 2,3- and 4,6-diols for O-methyl d-mannoside with TIPS-ADMA and selective deprotection of the acetals have been achieved.     

A one-step procedure for the monoacylation of symmetrical 1,2-diols

A series of lanthanide (III) salts have been shown to catalyze the monoacylation of symmetrical 1,2-diols by carboxylic acid anhydrides with surprisingly high selectivity.     

Reactions of 1,2-bis(trimethylsilyloxy)cycloalkenes with the diethyl acetals of aldehydes

[reaction: see text] Lewis acid-mediated reactions of 1,2-bis(trimethylsilyloxy)cyclobutene with acetals derived from a variety of aldehydes, followed by treatment with Amberlyst 15 resin in TFA, yielded 1,3-cyclopentanedione products, but reactions with 3,3-dimethyl-1,2-bis(trimethylsilyloxy)cyclobutene led to 1,2-cyclopentanediones. Reactions of 1,2-bis(trimethylsilyloxy)cyclopentene gave intermediates that did not undergo skeletal rearrangement with Amberlyst 15 resin in TFA.     

New syntheses of diaza-crown ethers using boc protecting groups

BOC-protected m-xylylenediamine was treated with tetraethyleneglycol ditosylate to form BOC-protected diazabenzo-18-crown 5 (5) in a good yield. BOC-protected diazabenzo-21-crown-6 (6) was prepared in the same manner from BOC-protected m-xylylenediamine and pentaethylene glycol ditosylate. Bis-BOC-protected diaza-17-crown-5 (12) was prepared by treating BOC-protected 1,4-diaminobutane with 1,11-diiodo-3,6,9-trioxaundecane. The BOC-protecting groups were removed in methanolic 2 N hydrogen chloride to form the corresponding diaza-crown ethers 7, 8 and 13 .     

A mild procedure for the conversion of 1,2-diols to olefins

An improved procedure for the stereospecific synthesis of olefins from 1,2-diols via the corresponding thionocarbonate is described.     

Ketene bis(trimethylsilyl) acetals. Cross-aldol type condensation reactions with aldehydes and schiff bases

Condensation of the title acetals with aldehydes and Schiff bases in the presence of titanium tetrachloride is reported for the first time. It leads to β-hydroxyacids and to β-lactams via a cross-aldol type reaction, with good yields.     

Rearrangements accompanying fluorination of 2-amino alcohols and 1,2-diols with Deoxo-Fluor™

2-Amino alcohols and 1,2-diols treated with Deoxo-Fluor™ in methylene chloride resulted in the formation of rearranged major products concomitantly with minor amounts of the straightforward fluorinated replacement products in good yields.     

Stereoelectronic effects in the reactions of conformationally restricted,substituted cyclohexane-1,2-diones with 1,2-diols

The asymmetric synthesis of a C₂-symmetric cyclic 1,2-diketone is reported along with investigations into its properties as a potential asymmetric protecting group for 1,2-diols as the corresponding 1,2-diacetal.