Alcohols solid support

Various solid-supported perruthenate reagents have been designed for the oxidation of alcohols.Solid-supported NMO has also been used. A number of perruthenate systems employing O2 as the terminal oxidant have also been reported. The use of ionic liquids based upon substituted imidazolium cations as alternative solvent media for the selective oxidation of alcohols to aldehydes and ketones has also been investigated. ... 

AcOEt, AI2O3, 75-80°, 24 h, 45-69% yield. This method is selective for primary alcohols. Phenols do not react under these conditions. The use of Si02 NaHS04 as a solid support was also found to be effective. 

Cross-hnked polyacrylamides are a group of hydrophihc solid supports introduced primarily for preparation of biopolymers (Fig. 4). Unhke PS resins, polyacrylamides have excellent swelling capacity in both protic (water, alcohols) and aprotic (dichloromethane, dimethylformamide) solvents [88]. These beads are stable towards bases, acids, and weak reducing and oxidizing agents [89]. Predictably, conditions under which amide bonds are cleaved (i.e., sodium in liquid ammonia) [90] lead to rapid decomposition of the polymer. 

The synthesis and olefin metathesis activity in protic solvents of a phosphine-free ruthenium alkylidene bound to a hydrophilic solid support have been reported. This heterogeneous catalyst promotes relatively efficient ring-closing and cross-metathesis reactions in both methanol and water.200 The catalyst-catalyzed cross-metathesis of allyl alcohol in D20 gave 80% HOCH2CH=CHCH2OH. 

The use of the phenyl phosphate group as both a solid support attachment site and a crucial binding element represents what has been referred to as a pharmacophore-linking strategy [26]. We explored a variety of phenyl phosphate tether functionalities to provide resins varying in substitution pattern and in chemical flexibility (Scheme 1 and Table 4) [22]. All phenyl phosphate resins were synthesized in batch quantities of 20 g or more. Resin synthesis began with the addition of either /mnethoxy-benzyl alcohol or benzyl alcohol to commercially available bis(diisopro-pylamino)chlorophosphine, followed by addition of the diversity phenol [(Ri)-OFl, DIAT (diisopropylamino tetrazole)]. Displacement of the... 

Dihydropyran (DHP) linker 45 is a common handle that couples an alcohol to a solid support with subsequent release upon mild TFA conditions (Fig. 12) [54]. An alternative approach is to prepare an active carbonate linker. TV,TV -Disuccinimidyl carbonate (DSC), a valuable reagent for converting hydroxymethyl-based supports to their corresponding carbonates, was reacted with 4-hydroxymethylpolystyrene 46 and 4-nitrobenzamido (Nbb) 47 resins to anchor alcohols and phenols (Scheme 17) [55]. The final products were released from the solid support by HF and photolysis, respectively. 

Thompson LA, Ellman JA. Straightforward and general method for coupling alcohols to solid supports. Tetrahedron Lett 1994 35 9333— 9336. 

In a related and more recent study by the same group, syntheses of various solid-supported acylating agents for microwave-mediated transformations of amines, alcohols, phenols, and thiophenols have been presented [129]. In a microwave-mediated... 

Varma and coworkers have explored the use of hypervalent iodine compounds on solid support for the first time and developed a facile oxidative procedure that rapidly converts alcohols to the corresponding carbonyl compounds using alumina-sup-ported IBD under solvent-free conditions and MW irradiation in almost quantitative yields [108]. The use of alumina as a support improved the yields markedly as compared to neat IBD (Scheme 6.33). 1,2-Benzenedimethanol, under these conditions, undergoes cyclization to afford l(3H)-isobenzofuranone. 

Immobilized catalysts on solid supports inherently have benefits because of their easy separation from the products and the possibility of recycling. They are also expected to be useful for combinatorial chemistry and high-throughput experimentation. The polystyrene-bound BINAP/DPEN-Ru complex (beads) in the presence of (CH3)3COK catalyzes the hydrogenation of l -acetonaphthone with an SCR of 12 300 in a 2-propanol-DMF mixture (1 1, v/v) to afford the chiral alcohol in 97% ee (Fig. 32.35) [113]. This supported complex is separable... 

A novel development for HPLC is something called bonded reversed-phase columns, where the stationary phase is a nonpolar hydrocarbon, chemically bonded to a solid support. You can use these with aqueous eluents, usually alcohol-water mixtures. So you have a polar eluent and a nonpolar stationary phase, something that does not usually occur for ordinary wet-column chromatography. One advantage is that you don t need to use anhydrous eluents (very small amounts of water can change the character of normal phase columns) with reversed-phase columns. 

Scheme 10 7 Solid-supported glycosylation of a hindered saccharide alcohol.

A very unusual Nazarov cyclization of propargyl vinyl ketones has been reported by Hashmi et al. (Eq. 13.16) [18]. Propargyl alcohol 50 was oxidized to ketone 51 with the Dess-Martin periodinane. Attempts to purify 51 by column chromatography on silica gel led to cyclopentenone 53 in 59% isolated yield. This suggests that the solid support catalyzed the isomerization of 51 to allenyl vinyl ketone 52, which was not isolated, but which underwent spontaneous cyclization to 53. This result is consistent with earlier observations of the great ease with which allenyl vinyl ketones undergo the Nazarov reaction (cf. 8, Eq. 13.2). 

Primary and secondary alcohols are oxidized slowly at low temperatures by benzyltriethylammonium permanganate in dichloromethane primary alcohols produce methylene esters (60-70%), resulting from reaction of the initially formed carboxylate anion with the solvent, with minor amounts of the chloromethyl esters and the carboxylic acids. Secondary alcohols are oxidized (75-95%) to ketones [34] the yields compare favourably with those obtained using potassium permanganate on a solid support. 1,5-Diols are oxidized by potassium permanganate under phase-transfer catalytic conditions to yield 8,8-disubstituted-8-valerolactones [35] (Scheme 10.1). 

Oxidations of various organic functional groups such as alcohols or alkenes are some of the most important transformations in organic chemistry. Unfortunately, their use is sometimes restricted hy poor selectivities or the need for transition metals and other species, which might be toxic or difficult to remove during work-up. Therefore, numerous attempts have been made to immobihze oxidants on a solid support [4], and these are compiled in the following. 

Oriyama subsequently showed that this catalyst system was also effective for the KR of various classes of iec-alcohols, notably P-halohydrins [188] and also certain a-chiral primary alcohols such as glycerol derivatives [184], A solid-supported version of Oriyama s catalyst developed by Janda was found to which induce comparable levels of selectivity [185-187],... 

Organic compounds such as lactic acid [74, 75], citric acid [74], fumaric acid [76, 77], and amino acids [74] were also shown to catalyze the ROP of lactones, using alcohols and amines as initiators. Interestingly, an acid catalyst can be supported on a solid support such as porous silica [78]. Unfortunately, the polymerization is slow and reuse of the catalyst after its recovery and regeneration turned out to be unsuccessful. Finally, it is worth noting the particular behavior of amino acids, which are able to both catalyze and initiate the ROP of lactones [79]. 

Figure 6.11 Typical tridentate ligand structure incorporating a chiral amino alcohol and modified diamine-based tridentate ligand structure attached to the solid support for parallel catalyst library strategy.

Z- and 4-alkoxyquinazolines are readily prepared by nucleophilic substitution reactions, and 2,4-dialkoxyquinazolines can simply be prepared by boiling 2,4-dichloroquinazolines with 2 equiv of an alkoxide in the appropriate alcohol solvent <1996HC(55)1>. The first substitution is in the more reactive 4-position, so it is possible to isolate both 4-alkoxy and 4-phenoxy monosubstitution products <1977EJM325, 2005BMC3681>, and this selectivity has been used to attach both 2,4,6- and 2,4,7-trichloroquinazoline to a solid support, via the 4-position, for subsequent solid-phase synthesis of 2,6- and 2,7-diamino-4(377)-quinazolinones <2003TL7533>. 

Cyanogen bromide reacts with amino alcohols to give 2-aminooxazolines that condense in the presence of benzaldehyde and p-toluenesulfonic acid with loss of ammonia to give aza-bis(oxazolines) 173. Aza-bis(oxazohnes) such as 173 are emerging as a new and important class of chiral ligands for asymmetric processes with the added advantage that they can be immobilized on solid supports (Scheme 8.50). 

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