Benzyl alcohols solid support

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... 

Iodosobenzene diacetate [IBD, PhI(OAc)2] is able to oxidize benzylic alcohols to benzaldehydes when a solid mixture of iodosobenzene diacetate and the alcohol is irradiated with microwaves. Best results are obtained when iodosobenzene diacetate is supported on alumina.118 The use of polymer supported iodosobenzene diacetate (PSDIB) simplifies the work-up in the oxidation of benzylic alcohols to benzaldehydes.119 PSDIB can be employed in the presence of KBr and using water as solvent, resulting in the transformation of secondary alcohols into ketones and primary alcohols into carboxylic acids.117... 

Caldarelli et al. (240) have recently reported a five-step synthesis of substituted p)Trole libraries L22 and L23 using solid-supported reagents and scavengers. The synthesis involved oxidation of benzyl alcohols Mi to aldehydes (step a, Fig. 8.46), Henry reaction of aldehydes 8.91 with nitroalkanes M2 (step b), and acylation and elimination of nitroalcohols 8.93 (steps c and d) to give the nitrostyrenes 8.94, which were subjected to 1,3-dipolar cycloaddition with an isocyanoacetate (step e) to give the pyrroles 8.95. N-alkylation of these pyrroles with alkyl halides (step f) and final library-from-a-library hydrolysis/decarboxylation of L22 gave a library of trisub-stituted pyrroles L23 (step g. Fig. 8.46). 

A recent example of the parallel synthesis of different quinazoline-2,4-dione derivatives (46) demonstrates how to combine the advantages of fluorous synthesis with those of solid-phase chemistry without using expensive perfluorinated solvents [22] (Scheme 3.22). In the beginning, a fluorous benzyl alcohol (47) is adsorbed on fluorous reversed-phase silica gel (FRPSG). Then, in a sequence of splits and reactions, the linker group, which remains bound to the FRPSG by fluorophilic interactions, is converted into a library of differently substituted carboxamido-urethanes (48). These are cyclized and the liberated quinazoline-2,4-diones (46) are eluted from the support with the fluorophobic solvents water and CHjCN/... 

TFA-CH2CI2 [191]. Ugi 4CC products prepared in solution from the interconvertible isonitrile may be captured on a solid support by nucleophilic attack of the benzylic alcohol of resin 5e on the cyclic dipole that is formed in the presence of acid carboxylic acids can then be released from the resin by treatment with TFA [192]. 

In combinatorial chemistry FRPSG can also be used as a solid support for organic synthesis. As a first example of this strategy, the synthesis of a library of 16 quinazoline-2,4-diones starting from perfluoro-tagged benzyl alcohol was described [74]. 

Solid-support-bound 1-aminoimidazolium chlorochromate 82 proved to be a selective oxidant for benzylic and cinnamylic alcohols <01S382>. Imidazolyl-A -difluoromethyltrimethylsilanes 83 are versatile sources of heteroaryl-A -difluoromethyl anions in reactions with carbonyl compounds <01SL374>. 

Finally, Chen s work on the direct allylation of carbonyl compounds using benzyl alcohol in the multicomponent Sakurai reaction catalyzed by selective and green solid acids, such as sihcomolybdic acid (SMA-SiO ) [92] or perchloric acid (HClO -SiOj) [93], both supported on silica gel, should be mentioned. In some cases, the use of preformed acetals as substrates provided better results. These methods allowed the synthesis of a broad number of homoallylic ethers in moderate to high yields in a short reaction time. Significantly, catalyst loading of HClO -SiOj is only 2mol%. 

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