Reactions, in solid phases

DMAP has been found to improve the coupling reaction in solid phase peptide synthesis (4). Polypeptides synthesized via the DMAP-DCC method were found to be of higher purity compared to other methods of synthesis. In polymer chemistry, DMAP has been used for hardening of resins and in the synthesis of polyurethanes, (5) polycarbonates, (6) and polyphenyleneoxides (7) ... 

BF Gisin, RB Merrifield. Carboxyl-catalyzed intramolecular aminolysis. A side reaction in solid-phase peptide synthesis. J Am Chem Soc 94, 3102, 1972. 

Scheme 3.11 Heck reactions in solid-phase synthesis [240].

T. Wehler and J. Westman, Magic angle spinning NMR A valuable tool for monitoring the progress of reactions in solid phase synthesis, Tet. Lett., 1996, 37, 4771-4774. 

Numerous examples of different variants of this cyclization/cleavage protocol have been reported. Diketopiperazine formation (Section 15.22.1), an unwanted side reaction in solid-phase peptide synthesis, is also an example of this type of compound release. Because intramolecular processes generally take place more readily than the corresponding intermolecular reactions, cyclization/cleavage can occur with alkyl... 

The acylation of amines on insoluble supports is one of the most thoroughly investigated reactions in solid-phase synthesis. The continuous optimization of peptide bond formation in recent decades has led to protocols that enable racemization-free, quantitative acylations of support-bound peptides with protected amino acids. In recent years, the range of amides available by solid-phase synthesis has expanded significantly to include, for example, N-alkylated peptides and anilides. New strategies for the preparation of amides, such as C-carbamoylations and the Ugi reaction, have also been successfully realized on insoluble supports. 

Scheme 45 Application of Mitsunobu reaction in solid phase synthesis of [1-lactam...

S. Brase, J. H. Kirchhoff, J. Kobberling, Palladium-Catalyzed Reactions in Solid Phase Organic Synthesis, Tetrahedron 2003, 59, 885-939. 

Yu K-L, Deshpande MS, Vyas DM, Heck reactions in solid phase synthesis, Tetrahedron Lett., 35 8919-8922, 1994. 

Svensson A, Fex T, Kihlberg G, Use of 19F NMR spectroscopy to evaluate reactions in solid phase organic synthesis, Tetrahedron Lett., 37(42) 7649-7652, 1996. 

This difference in activation energies is due to the specifity of reactions in solid phase, where the mobility of the reacting particles is greatly reduced. 

Taddei [7] has studied the use of the Barton decarboxylation reaction in solid-phase chemistry. FeasibiUty studies began with the preparation of simple immobihzed Barton ester 37 from Wang resin-derived acid 36 (Scheme 8). Irradiation of 37 followed by acid cleavage gave 38 in good overall yield. Attempts to prepare bromide 39 by interception of the intermediate radical... 

The reactions are first-order, after an induction period, and involve a small entropy of activation. The final products are KCl and oxygen. The rate parameters for reaction in solid phases are surprisingly close to those in melts, viz. 

Nielsen, T. E., Diness, F., Meldal, M. The Pictet-Spengler reaction in solid-phase combinatorial chemistry. Current Opinion in Drug Discovery Development 2003, 6, 801-814. 

Brase, S., Kirchhoff, J. H., Kobberling, J. Palladium-catalyzed reactions in solid phase organic synthesis. Tetrahedron 2003, 59, 885-939. Fairlamb, I. J. S. Transition metals in organic synthesis. Part 1. Catalytic applications. Annu. Rep. Prog. Chem., Sect. B, Org. Chem. 2003, 99,104-137. 

Syntheses of benzodiazepines by palladium-catalyzed reactions in solid phase 03T885. 

Grignard (-like) reactions are emerging solid-phase reactions that have not yet been exhaustively studied. One is, therefore, tempted to conclude that the use of Grignard reactions in solid-phase chemistry is under-developed. A reason might be that the high reactivity of Grignard reagents coupled with the need for anhydrous conditions complicates with solid supported synthesis. 

Often one of the steps in this domino reaction is a cycloaddition. A recent review by Dax et al. [Id] gives an overview of the state of the art of multicomponent reactions in solid phase synthesis. High pressure can play an important role in extending the scope of these reactions. 

Johnson, C.R. and Zhang, B. (1995) Solid phase synthesis of alkene using Homer-Wadsworth-Emmens reaction and monitoring by gel phase P NMR. Tetrahedron Lett. 36 9253-9256. Svensson, A., Fex, T. and Kihlberg, J. (1996) Use of F to evaluate reaction in solid phase organic synthesis. Tetrahedron Lett. 37 7649-7652. Swayze, E. E. 

Acetaldehyde/chloranil test, a monitoring method for the control of complete coupling reaction in solid-phase peptide synthesis [T. Voikovsky, Peptide Res. 1995, 8, 236]. 

Review on Pd-catalyzed reactions in solid phase synthesis S. Brose, J. H. Kirchhoff, and J. Kbbberling, Tetrahedron, 59, 885 (2003). 

As dicussed in Sec.1.Ill, general formulations of the equations for the rate constant are applicable, in principle, to both gas phase and dense phase reactions. The main dificulty in treating reactions in solution occurs when taking into account the influence of the solvent. Including the interactions between the reactants and solvent molecules is necessary for an accurate treatment based on a manydimensional potential energy surface of the whole system (reactants + solvent). This is at present an extremely complicated task. The unique way out of this difficulty is to introduce simplified models for different types of reactions which take into account the role of the solvent. The situation is simpler for reactions in solid phases, where vibrations of atoms and molecules are usually the only modes of motion involved in the reaction. Neglecting translation and rotation motions in liquid media is also sometimes possible as an acceptable approximation. 

Erase, S., Kirchhoff, J.H. and Kobberling, J. (2003) Palladium in catalyzed reactions in solid phase organic s5mthesis. Tetrahedron, 59, 885-939. 

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