Anomeric activation of thioglycosides and preparation of deoxyglycosides using polymer-bound iodate(I) complexes

New thiophilic polymer-bound haloate(I) complexes are presented which are well suited for the polymer-assisted solution-phase activation of 2-deoxythioglycosides. In the presence of alcohols 2-deoxyglycosides are obtained in yields between 60 and 95%. Isolation of the target glycosides is further simplified by removing the byproduct diphenyldisulfide by reductive work-up. Here also a polymer-bound reagent, namely borohydride exchange resin, served as a tool for sequestering the sulfur-containing impurities.     

Pyridine assisted oxidations of alcohols to carbonyl compounds by means of 3-car☐ypyridinium dichromate (ndc) reagent

3-Car☐ypyridinium dichromate (NDC),readly prepared from nicotinic acid and chromium trioxide, is an efficient reagent for the oxidation of alcohols into carbonyl compounds in the presence of pyridine. The optimum molar ratio substrate:reagent:pyridine to ensure complete oxidation of starting material in a short reaction time was found 1:2.5:20 respectively. A brief comparison between this reagent and pyridinium dichromate (PDC) is made. In contrast to the PDC reagent, NDC allows selective oxidation between benzylic alcohols and aliphatic alcohols. The NDC-pyridine system has been successfully extended to the oxidation of N-(2-hidroxy-2-phenyl or 2-methylethyl)-β-lactams into their corresponding carbonyl compounds as N-H azetidin-2-one precursors. In contrast, primary N-(2-hydroxyethyl)-β-lactams upon treatment with this reagent system afforded N-formylazetidin-2-ones.The influence of pyridine in oxidations by means of NDC is further shown in the conversion of hydroquinones into quinones. Another interesting feature associated with the use of this reagent is the ease of purification of the final products.     

Modification of the Swern Oxidation: Use of Stoichiometric Amounts of an Easily Separable, Recyclable, and Odorless Sulfoxide That Can Be Polymer-Bound

Readily available 6-(methylsulfinyl)hexanoic acid (1) is employed as a substitute for DMSO in Swern oxidation reactions using oxalyl chloride to smoothly convert primary or secondary alcohols to corresponding aldehydes or ketones in high yield. The resulting 6-(methylthio)hexanoic acid (2) is easily separable by aqueous extraction or by filtration through silica gel and can be reoxidized to 1 with sodium metaperiodate in 97% yield. Low temperature (-60 degrees C) (13)C NMR spectrometry is used to examine the intermediates of this Swern process. The results indicate that any residual unoxidized alcohol is generated during Pummerer elimination of the alkoxysulfonium intermediate and can be minimized by extended exposure to triethylamine at -40 degrees C. Reaction of the potassium salt of 1 with cross-linked chloromethyl polystyrene affords a polymer-bound reagent 12 that quantitatively oxidizes borneol to camphor when used in two-fold excess.     

Oxidation with a photolabile carbonyl protecting group

A novel oxidation approach utilizing a robust photolabile carbonyl protecting group reagent (1) as the oxidizing reagent has been developed. Different from existing methods, this approach oxidizes primary alcohols to the photosensitive acetals (e.g., 3), providing another unique approach to the protected aldehydes. Thus, for the first time, oxidation and protection are achieved in one reaction. Secondary alcohols are oxidized to the corresponding ketones. Moreover, the photolabile protecting group (PPG) also oxidizes ethers and esters. The oxidation is presumably via hydride abstraction by the tritylium ion generated from 1 under acidic conditions. However, the mechanisms for primary alcohols and secondary alcohols are slightly different.     

Stable Polymer-Bound Iodine Azide

1,2-Azido-iodination of a wide range of alkenes under very mild conditions can be achieved by using a novel iodate(I ) reagent, a stable and storable polymer-bound iodine azide, which is available in two steps (see scheme). Simple work-up and convenient use in automated parallel synthesis are important features of this polymer-bound reagent.     

氯铬酸甲铵/硅胶载体氧化剂的制备及其对醇的氧化研究

利用硅胶作载体，负载氯铬酸甲铵盐制备了一种新的载体铬(Ⅵ)氧化剂。该试剂制备方法简单、性质稳定。可在多种反应介质中对伯醇和仲醇氧化，高收率得到相应的醛和酮，反应操作简单，提纯方便。     

Application of a solid-phase beta-triphosphitylating reagent in the synthesis of nucleoside beta-triphosphates

A beta-triphosphitylating reagent was subjected to reaction with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound beta-triphosphitylating reagent. The solid-phase reagent was reacted with unprotected nucleosides (e.g., 3'-azido-3'-deoxythymidine, cytidine, thymidine, uridine, inosine, or adenosine) in the presence of 1H-tetrazole. Polymer-bound nucleosides underwent oxidation with t-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford only monosubstituted 5'-O-beta-triphosphorylated nucleosides.     

A novel and selective oxidation of benzylic alcohols with polymer-supported periodic acid under mild aprotic conditions

A new polymeric oxidizing reagent was prepared by supporting periodic acid on poly（1,4-phenylene-2,5-pyridine dicarboxyamide）. This polymeric reagent was used for the selective oxidation of primary benzylic alcohols to the corresponding benzaldehydes in CH₃CN at reflux conditions.Excellent selectivity was observed between primary benzyl alcohols and secondary ones as well as non-benzylic alcohols in the oxidation reactions.Allylic alcohols were also converted to the corresponding aldehydes with good yields.     

Deracemization of 1,2-diol monotosylate derivatives by a combination of enzymatic hydrolysis with the Mitsunobu inversion using polymer-bound triphenylphosphine

The deracemization of 1,2-diol monotosylate derivatives is achieved by the sequential combination of enzymatic hydrolysis and Mitsunobu inversion using a polymer-bound triphenylphosphine. After the lipase-catalysed hydrolysis of the racemic 2-acetoxyhexyl tosylate, the subsequent Mitsunobu reaction without separation causes an inversion of the resulting (R)-alcohol to give the (S)-enantiomer of the acetate as a single product. In particular, the reaction using the polymer-bound triphenylphosphine also proceeds smoothly, and the product is easily separated by filtration from the polymer-bound reagent and its by-products. This deracemization process is applicable to the preparation of several optically active 1,2-diol monotosylates.     

盐酸三甲胺三氧化铬／硅胶对醇类化合物的氧化研究

报道了盐酸三甲胺三氧化铬／硅胶对醇类化合物的氧化反应。盐酸三甲胺三氧化铬／硅胶可在多种介质中氧化伯醇和仲醇成为相应的醛或酮，反应条件温和、操作简单、收率高。     

4-Benzylpyridinium Fluorochromate: An Efficient and Selective Oxidant for Organic Substrates

A new chromium(VI) reagent, 4-benzylpyridinium fluorochromate, was prepared and used for oxidation of various organic substrates under solvent-free conditions. The reagent selectively converts primary benzylic alcohols to their corresponding carbonyl compounds in the presence of primary aliphatic alcohols.     

Polymer-bound oxathiaphospholane: a solid-phase reagent for regioselective monothiophosphorylation and monophosphorylation of unprotected nucleosides and carbohydrates

Two polymers bound to N,N-diisopropylamino-1,3,2-oxathiaphospholane were reacted with unprotected carbohydrates and nucleosides in the presence of 1H-tetrazole, followed by oxidation with tert-butyl hydroperoxide or sulfurization with Beaucage's reagent. The 1,3,2-oxathiaphospholane ring-opening with 3-hydroxypropionitrile, followed by treatment with DBU, afforded the corresponding monophosphate and monothiophosphate derivatives, respectively, through the elimination of polymer-bound ethylene episulfide. Reactions using this strategy offer the advantages of high regioselectivity, monosubstitution, and facile isolation and recovery of products.     

4-Benzylpyridinium Fluorochromate: An Efficient and Selective Oxidant for Organic Substrates

Summary. A new chromium(VI) reagent, 4-benzylpyridinium fluorochromate, was prepared and used for oxidation of various organic substrates under solvent-free conditions. The reagent selectively converts primary benzylic alcohols to their corresponding carbonyl compounds in the presence of primary aliphatic alcohols.     

Solid-supported solution-phase synthesis of 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones

Starting from Boc-o-aminomethylphenylalanine, a solution-phase parallel synthesis of 2,4-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described. This heterocycle has two nitrogen functions, which are differentiated and can be selectively substituted. The sources of diversity are aldehydes for the R(1) position and carboxylic acids, sulfonyl chlorides, or isocyanates for the R(2) position. High-throughput synthesis and purification of this multistep synthetic sequence was accomplished using polymer-bound reagents and scavengers and liquid-liquid extraction protocols, and a small library of compounds was prepared. Polymer-bound cyanoborohydride was found to work well for the reductive amination. Scavenging of excess of amine was performed by polymer-bound benzaldehyde, and cyclization was performed in the presence of polymer-bound coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). After Boc-deprotection, the second nitrogen can be acylated using carboxylic acids, sulfonylated or converted to a urea. The acylation is again performed by polymer-bound EDC. Excellent yields and purities were obtained.     

A regenerable immobilized nadh model IV: Reduction of pyridine-2-carbaldehyde by immobilized 1,4-dihydronicotinamide in the presence of Mg2+ ions

Dihydronicotinamide, anchored to a macroreticular polystyrene resin, reduces pyridine-2-carbaldehyde (PCA) in the presence of Mg²⁺ ions in acetonitrile. The reactions are clean at room temperature, the high rate precluding complications arising from slow side reactions. The influence of Mg²⁺ concentration on the rate of reduction of PCA by polymer-bound reagent and BNAH (1-benzyl-1,4-dihydronicotinamide; low-molar-mass analog) has been studied. Analysis of the kinetic data showed that of the processes contributing to the overall reduction, the reaction between the reductant and the complexed substrate proceeded at the highest rate. In the polymer-bound reagent, “site isolation” on the rigid matrix was observed to prevent bimolecular disproportionation of the neighboring dihydronicotinamides. Regeneration of the polymeric reagent was achieved with an efficiency of 98% per cycle.     

Using soluble polymers in latent biphasic systems

A new strategy for carrying out reactions with a soluble polymer-bound reagent or catalyst is described. In this latent biphasic process, a solvent mixture at the cusp of immiscibility is prepared and used to carry out a reaction under homogeneous conditions. Then, after the reaction is complete, this mixture is perturbed by the addition of solvent or some other perturbing agent to produce a biphasic mixture. The product-containing phase is then separated under liquid/liquid conditions from the polymer-containing phase. The generality of this process is demonstrated using both dye-labeled polymers as surrogates for polymer-bound catalysts and with various polymer-bound organic and transition metal catalysts or reagents. In cases where a polymeric catalyst is used, the addition of fresh solvent and substrate reforms the original mixture allowing facile reuse of the catalyst.     

The TEMPO/Copper Catalyzed Oxidation of Primary Alcohols to Aldehydes Using Oxygen as Stoichiometric Oxidant

Summary. A catalytic system for the selective oxidation of primary alcohols to aldehydes under very mild conditions was developed. The catalytic system is based on TEMPO and Cu(II), which is generated in situ by oxidation of elemental copper and chelated by means of 2,2′-bipyridine. Compared to existing Cu/TEMPO oxidation methods we substantially lowered the amount of copper necessary and discovered that the reaction is dependent on pH. The catalytic system was also tested with polymer-bound TEMPO and new insights into the currently discussed mechanism were derived.     

Fast oxidation of secondary alcohols by the bromate-bromide system using cyclic microwave heating in acidic water

We report an improved, gentle, cyclic microwave activation technique for the oxidation of secondary alcohols using nonhazardous hypobromous acid (BrOH) as the reagent in acidic water. Several aliphatic and aromatic secondary alcohols were successfully oxidized to the corresponding ketones using this technique in high yields and with only minor amounts of side products.     

Macroporous polystyrene-supported IBX amide: the improved oxidative properties in various solvents

In this study, macroporous polystyrene-supported IBX (MPS-IBX) amides were prepared in two simple steps, and the polymeric reagent was then evaluated for its efficiency in converting a range of alcohols to the corresponding carbonyl compounds in various solvents. The results indicated that the MPS-IBX amides were compatible with a variety of solvents, and had a more efficient oxidation activity toward alkyl alcohols than the gel type polystyrene-supported IBX amides. Finally, the resin that was consumed in the oxidation reaction was regenerated to give a restored loading level of 0.44-0.54 mmol/g.