Procedure: Attachment of alcohols to theTHP-based linker 37 and release from the linker 3,4-Dihydro-2H-pyran-2-ylmethoxymethyl polystyrene 37 is commercially available (Nov-abiochemj. Alcohols (5 equiv.; 0.4 M in DCE) were loaded onto 37 in the presence of 2 equiv. of PPTS at 80° C for 16 h. Alternatively, the coupling is also possible with p-TsOH at 0° C for 16 h.
Procedure: Cleavage from 38
0.74 mmol (1 g of support 38) in 20 mL of a mixture of DCE/butanol (1:1) and 1.48 mmol (370 mg) PPTS in a closed flask were heated to 60° C for 16 h. After filtration, the solution was evaporated.The product can be separated from PPTS or p-TsOH by extraction or chromatography. Alternatively, the cleavage can be performed withTFA/water (95:5).
Several examples have appeared in the literature applying this linker to combinatorial chemistry strategies. Thus, it has been used for a Pd-mediated three-component coupling strategy for the solid-phase synthesis of tropane derivatives , for the solid-phase synthesis of aspartic acid protease inhibitors , for the attachment of a cholic acid as template for a combinatorial approach  and, more recently, for the solid-phase synthesis of pyrrolidines via 2-azaallyl anion cycloadditions with alkenes ,
An impressive total synthesis of prostaglandin F2a was achieved on this linker . The starting material 39 was transformed in a multistep synthesis to the polymer-bound target molecule 40. Compound 41 was then released in good yield and high purity with 48 % aqueous HF/THF (3:20; v/v) (Scheme 20).
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