Pseudo-dilution

A newer process for preparation of mixtures of cycHc oligomers has been discovered (15,35). This process utilizes a triethylamine-catalyzed hydrolysis condensation of BPA bischloroformate in a pseudo-dilution reaction. This efficientiy provides 85—90% yield of a mixture of cycHc oligomers having a degree of polymeriza tion of 2 to about 12 (eq. 12). 

To cyclize resin bound diene substrates by RCM in this specific case, the pseudo dilution conditions within the polystyrene matrix may favor ring closure over competing polymerization of the substrate via ADMET... 

Diisonitriles 98 and 101 were subsequently employed in a double Ugi macrocyclization reaction under pseudo-dilution conditions, where the di-... 

The principle of oxidation of bis-cysteine peptides on resin consists of deprotection and oxidation of a cysteine pair in a single step or in two separate steps to form the disulfide bond while the peptide chain remains attached to the solid support. The strategy is especially effective for the formation of intramolecular disulfides since the solid support simulates high dilution via the pseudo-dilution effect, thus, largely preventing intermolecular reactions. 163 98 10° ... 

Conditions Heterogeneous (resin swelling) Homogenous (pseudo dilution) Homogenous (1 M)... 

It should be mentioned, however, that high dilution is still mandatory in order to obtain high yields [15, 16], which can be achieved either by low feeding rates of the substrate into the solution containing the catalyst or by exploiting the pseudo-dilution effect of polymer bound Pd° [41]. This experimental requirement shows that the palladium center itself does not shape the substrate but just stabilizes the reactive eonformation once it is adopted (Scheme 9-21). Therefore the observed template effect must be largely attributed to electrostatic attraction and/or favorable ion pairing properties of the intermediates. 

Solid-phase synthesis offers several attractive features over solution-phase synthesis (1) Molecules are synthesized while covalently Unked to the solid support, facihtating the removal of excess reagents and solvents. (2) The solid-supported reaction can be driven to completion through the use of excess, soluble reagents. (3) Mechanical losses are minimized as the compound-polymer beads remain in single-reaction vessels throughout the synthesis. (4) Physical manipulations are easy, rapid, and amenable to automation. (5) The physical separation of the reaction centers on resin furnishes a pseudo-dilution (physi-... 

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