1,3-diol library

Silyl enol ethers are versatile reagents in organic synthesis [83]. They are used as isol-able enolate equivalents and many useful reactions have been developed using silyl enol ethers [83]. As a new approach to exploit an efficient method for combinatorial synthesis [84], silyl enol ethers were successfully immobilized on to a polymer. Polymer-supported silyl enol ethers (PSSEEs) were prepared according to Sch. 10 [85]. In aldol reactions of PSSEEs with aldehydes, it was again found that Sc(OTf)3 was an efficient catalyst [86]. An example of the preparation of a 1,3-diol library by use of PSSEEs is shown in Sch. 11. In all cases, the reactions proceeded smoothly to afford the corresponding 1,3-diols in good yields. 1,3-Diols are successfully cleaved from the... 

A combinatorial approach for biocatalytic production of polyesters was demonstrated. A library of polyesters were synthesized in 96 deep-well plates from a combination of divinyl esters and glycols with lipases of different origin. In this screening, lipase CA was confirmed to be the most active biocatalyst for the polyester production. As acyl acceptor, 2,2,2-trifluoroethyl esters and vinyl esters were examined and the former produced the polymer of higher molecular weight. Various monomers such as carbohydrates, nucleic acids, and a natural steroid diol were used as acyl acceptor. 

Thirteen different chiral diol ligands were used (Scheme 25), leading to a catalyst library of 104 members.121 In a model reaction benzaldehyde (51), (R = Ph) was used as the carbonyl component, HPLC being used to ascertain the enantiopurity of (92). Initially 1 mol.% of catalyst was used. In the primary screening catalysts modified by L4, L5, L6, and L7 turned out to be excellent (77-96% ee yields 63-100%). Thereafter the catalyst loading of Lm/Ti/Lra (m, n = A-l) was decreased to 0.1 mol.%, but this led to only trace amounts of product. Finally, the solvent was... 

A similar approach to create an oligosaccharide library was reported using a glycal and diols as the donor and acceptor to produce stereospecific regiorandom mixture of glycosides (Fig. 12.12).15 a-Specific glycosylations were achieved via addition of... 

Figure 12.12 Formation of an oligosaccharide library using glycal and diols as donor and acceptor, respectively, to produce a stereospecific regiorandom glycoside mixture.

The DMAP derivative 19a was tested for kinetic resolution of a variety of mono esters of cyclic cis diols (rac-20a-i) (Scheme 12.5) [15]. Catalyst 19a afforded selectivity factors up to 12.3 and highly enantioenriched mono esters 20 with conversions of 65-73%. For this type of reaction the selectivity of the Campbell catalyst 19b was similar (selectivity factor 13.2, Scheme 12.5) [16a], The latter catalyst was identified by screening of a 31-mer library prepared from the parent N-(4-pyridyl)-a-methylproline and a variety of amines [16a], The solid-phase-bound forms of N-(4-pyridyl)-a-methylproline, as reported by Anson et al. [16b], are easily recyclable acylation catalysts affording selectivity factors up to 11.9 in the kinetic resolution of the secondary alcohol rac-20b (Scheme 12.5). In the kinetic resolution of N-acylated amino alcohols, selectivity factors up to 21 were achieved by use of the Kawabata-Fuji catalyst 19a, and up to 18.8 by use of the Campbell system 19b (Scheme 12.5) [15, 16a]. 

Selectivity in enantiotopos-differentiating acylation and phosphorylation of meso-diols can rival that of enzymes. The organocatalysts employed include chiral phosphines, chiral diamines, chiral DMAP derivatives and peptides identified from combinatorial libraries. The highest selectivity in meso diol desymmetrization has been achieved with a planar-chiral Fu catalyst. It seems the substrate scope of this process is not yet broadly explored. Because of their sequential variability it is to be... 

The solvent-free asymmetric Hetero-Diels-Alder reaction of 14 different aldehydes with Danishefsky s diene was carried out with 0.1-0.005 mol% of chiral titanium complexes to afford dihydropyrones with up to quantitative yields and 99.8% ee. A library of chiral metal complexes was generated by combining one or two different chiral diol ligands e.g. 5 (13 different diols were applied) with titanium isopropylate (Scheme 16) [46],... 

A couple of ortho- and mefa-substituted structures that were regarded as particularly interesting were chosen for re-synthesis on a slightly larger scale with thorough chemical characterization of the isolated inhibitors. In order to decrease the formation of side products detected in the initial library syntheses, it was decided to protect the central vicinal diols of the aryl halide... 

Aldol condensation of the zinc enolate of resin-bound alkyl ester 29 with aromatic aldehyde or ketone forms a P-hydroxy ester, which upon treatment with DIBAL-H leads to simultaneous reduction and cleavage of the ester moiety from the resin to give a soluble 1,3-diol 31 [31], Parallel synthesis utilizing three ester and nine carbonyl building blocks afforded a library of 27 analogs which was screened for antioxidative efficiency using a ferric thiocyanate assay. 

Kobayashi et al. reported the first synthesis of polymer-supported silyl enolates (thioketene silyl acetals) and their reactions with aldehydes for the preparation of 1,3-diol, / -hydroxy carboxylic acid, and /i-hydroxy aldehyde libraries (Scheme 10.37) [104]. In the presence of 20 mol% Sc(OTf)3, polymer-supported silyl enolate 42 derived from chloromethyl copoly(styrene-l% divinylbenzene) resin via 41 reacts smoothly with a variety of aldehydes. The resulting adducts can be easily purified by acid treatment and subsequent washing with water and organic solvents. The purified adducts are converted into 1,3-diols with LiBH4, -hydroxy carboxylic acids with NaOH, and -hydroxy aldehydes with DIBALH. This strategy has been used for efficient synfhesis of diverse monosaccharide derivatives [105]. 

A library of resin bound furans 294-296 with diverse appendages were prepared and oxidized. Those furans with appended diols gave bicyclic acetals 297, those with a single alcohols the hydropyrones 298 that underwent dehydration and those without a hydroxyl gave the open-chain compounds, thus generating three structural types from a common intermediate. This last diversity-oreiented example nicely illustrates the synthetic flexibility and power offered by the use of furans. It is certain that the role of furan in complex-molecule synthesis will continue to expand in many new directions. 

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