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Solid-phase organik syntheses - Burdges K.

Burdges K. Solid-phase organik syntheses - John Wiley & Sons, 2000. - 283 p.
ISBN 0-471-22824-9
Download (direct link): phaseorganicsynthesis2000.pdf
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A single, functionalized resin can be designed to capture more than one reactant. For instance, resin 3 has been used to sequester excess aldehydes/ketones and thioacetic acids.28 Specifically, the poly amine resin 3 did this by forming the resin-bound thiazolidinones 11 and salts from the excess reagents, leaving the desired thiazolidinones in solution.
Me
Me
OH
(1)
OH
(excess reagents sequestered on resins)
j
amine resin 3
156 POLYMER-ASSISTED SOLUTION-PHASE METHODS
5.3. BYPRODUCT SEQUESTRATION
Byproduct sequestration using a supported functional group (cBp in the diagram below) complementary to that of byproduct is a logical extension of reactant sequestration. There are fundamental differences between the two methods, however. Reactant-sequestering resins are exclusively used after solution-phase reactions to remove excess substrates, whereas byproduct-sequestering resins can be present during or after the transformation. One advantage of adding a capture agent to a reaction in progress is that byproduct-sequestering resins can drive equilibrium reactions to completion. A second distinction is that reactant sequestration usually involves covalent bond formation with a functionalized resin, whereas byproduct sequestration typically relies on ion-pairing (acid-base) interactions.
A + Â -----------------> product + byproduct
Carboxylic acids generated in acylation reactions have been effectively sequestered by ion pair formation with Amberlite IRA-68 ion exchange resin.29’3 Similarly, 4-nitrophenoxide formed in acylations of 4-nitrophenyl esters has been captured by anion exchange with the quaternary ammonium hydroxide resin 12.31 An exception to ion pair-mediated sequestration of byproducts is the polyamine functionalized resin 3 that was shown to covalently sequester the (3-methoxy enone hydrolysis byproduct from Dan-ishefsky’s diene via imine formation.23
It is anticipated that additional byproduct-sequestering resins will be reported in the near future, highlighting novel ionic and covalent sequestration strategies. In particular, the application of byproduct-sequestering resins (other than acid scavengers) to help drive reactions to completion would demonstrate a significant advance in this area.32
cBP
sequestered byproduct
12
5.4. SOLUTION-PHASE DERIVATIZATION 157
5.4. SOLUTION-PHASE DERIVATIZATION TO FACILITATE POLYMER-ASSISTED SEQUESTRATION
5.4.1. Reactant Solution-Phase Linking Reagents
Direct sequestration of a reactant by an insoluble resin is impractical if the kinetics is sluggish and impossible if the solution-phase reactant does not contain a functionality to enable direct sequestration. These limitations led
several research groups to use “bifunctional solution-phase linking reagents,” also referred to as “sequestration-enabling-reagents.”33
A + Â -------------> product + byproduct
In a typical process N,N-dimethyl-ethylenediamine has been used to transform excess isocyanate reactants into amine-tagged ureas that can be sequestered from solution phase.34,35 Glycine has been used as a carboxy-tagged solution-phase linking reagent to convert aldehydes or isothiocy-anates to the carboxy-tagged imines or thioureas, respectively.36 Similarly, the more nucleophilic sarcosine salt 13 has been used to derivatize isocyanates, acid chlorides, or sulfonyl chlorides as carboxy-tagged derivatives (equation 3). 37 Finally, the carboxy-tagged thiourea 14 was utilized to convert excess a-bromoketones to carboxy-tagged aminothiazoles for capture by ion exchange resins.34
+ excess A
bifunctional linking reagent v Y-X
cY-Y-X-A ^
Y__x—A
resin sequestered functionalized reactant
H H
RNCO +
³
(2)
Me
Î
Me
can be sequestered on acidic ion-exchange resin
158 POLYMER-ASSISTED SOLUTION-PHASE METHODS
R—N=C=0
or H X
RCOCI +Me"N^C°2,C-----------^ (3)
or x = rso2, rco
rs°2C| 13 or RNHC0
A few solution-phase linking reagents facilitate sequestration of modestly reactive nucleophiles. Tetrafluorophthalic anhydride was shown to be sufficiently reactive to derivatize electron-deficient and sterically hindered anilines, amines, and alcohols as the carboxy-derivatized species 15.32,33 Benzenesulfonyl isocyanate was also shown to efficiently derivatize anilines, amines, or alcohols, forming acidic sulfonylureas or sulfonylcar-bamates 16, which can be sequestered on a polyamine-functionalized resin. Use of these highly reactive soluble linking reagents facilitated purification of products even from low-yielding, incomplete reactions. Finally, hcxafluoro-/.w-propyl oxalate was used to convert poorly reactive anilines to their sequestrable half-esters 17.38 These anilines did not further react to form bis-amides, so preserving a hexafluoro-wo-propyl ester for covalent sequestration by a polyamine-functionalized resin.
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