Electrophiles solid-supported

This symposium addressed several important issues in bromine chemistry. A major part has been devoted to stereochemistry and mechanism of electrophilic bromination of olefins. Other topics included new selective methods of bromination and oxybromination, brominations in presence of solid supports and catalysts, organobromine compounds as synthons, recent developments in brominated fire retardants and toxicological and environmental aspects of brominated compounds. 

Kaldor SW, Siegel MG, Dressman BA, Hahn PJ (1996) Use of solid supported nucleophiles and electrophiles for the purification of non-peptide small molecule libraries. Tetrahedron Lett 37 7193-7196... 

S. W. Kaldor, M. G. Siegel, J. E. Fritz, B. A. Dressman, P. J. Hahn, Use of Solid Supported Nucleophiles and Electrophiles for the Purification of Non-Peptide Small Molecule Libraries , Tetrahedron Lett. 1996,37,7193-7196. 

Most conventional scavenging is based on the concept of complementary reactivity. In the simplest cases, electrophilic and nucleophilic species are sequestered via a reciprocally functionalized support (Scheme 2.11 see also Tab. 2.1) likewise, acids and bases can be removed via salt formation with a solid-supported base or acid. 

Kaldor [49 i, 55] demonstrated the advantages of applying solid-supported scavengers to the preparation of parallel arrays in a multi-step fashion. In these studies he examined the clean-up of multiple amine alkylation and acylation reactions using a variety of immobilized electrophilic and nucleophilic scavenger reagents including an amine, isocyanate, aldehyde and acid chloride (Tab. 2.1). 

Recently, the semi-synthesis of Vancomycin (48) on solid supports was accomplished using an allylic linker (Scheme 3.2) [123, 124]. Polymer-bound chiral electrophilic selenium reagents have been developed and applied to stereoselective se-lenylation reactions of various alkenes (Tab. 3.9) [125]. 

Recently, Price and and Osborne have developed a synthetically convergent route to produce libraries of Af-formylhydroxylamines that utilizes commercially available starting materials. In particularly, they have investigated the reaction of several electrophiles with the nitrogen atom of a solid-supported 0-protected A-formylhydroxylamine 221. 

Among the electrophilic handles proposed for head-to-tail and side-chain-to-tail cyclization of peptides on solid support by intrachain aminolysis with concurrent detachment of the product from the resin in the protected form (see Section 6.8.3.1.3), generally the oxime resin (also called Kaiser resin)1364 365 and a thioester resin[363l are recommended (see Scheme 14). In addition to the classical head-to-tail cyclization,[3431 the oxime resin is used for side-chain cyclizations as well as for the synthesis of multicyclic peptides vide infra). Due to its dual functions, the oxime resin can be employed only with Boc/Bzl chemistry it is not compatible with Fmoc/tBu chemistry where the basic N -deprotection leads to free amino groups and thus to premature cyclization reactions. To avoid this premature cleavage of the... 

The enzymes used to generate reactive quinone methides often undergo inactivation by addition of this electrophile to essential nucleophilic amino acid side chains of the protein catalyst. This is a type of suicide enzyme inhibition.80 This was observed for the acid phosphatase and ribonuclease catalysts used to generate 43.76 79 Alkaline phosphatase has been used to remove the phosphate protecting group from a derivative of an o-difluoromethyl phenyl phosphate that was covalently attached to a solid support. Breakdown of the immobilized 4-hydroxybenzyl difluoride gives an immobilized quinone methide that, in principle, will react irreversibly with proteins and lead to their attachment to the solid support.81... 

This strategy has previously been referred to as t A nucleophilic polymer is a scavenger of solid-supported scavengers (SSS), polymer- electrophiles and vice versa,... 

Several types of electrophilic selenium species have been immobilized on solid supports, for more convenient application to organic synthesis. These include selenenyl halides, " selenocyanates, and selenosulfonates. ... 

Benzothiazoles are most commonly prepared by the ring closure of o-aminobenzothiazoles. This methodology has been well reviewed in both CHEC(1984) <1984CHEC(6)235> and CHEC-II(1996) <1996CHEC-II(3)373>. Typically an o-aminothiophenol is reacted with a suitable electrophile such as an aldehyde, a carboxylic acid, or an ester in a suitable solvent at reflux to provide the desired benzothiazole. Acid chlorides have also been used. The use of esters usually requires harsh conditions, but when the ester is bound to a solid support 241, it has been found that the addition of o-aminothiophenol in the presence of AlMes or Et2AlCl as Lewis acid produces the benzothiazole 242 in what has become known as a smart cleavage reaction (Scheme 97) <2004TL313>. 

Density functional theory (DFT) provides an efficient method to include correlation energy in electronic structure calculations, namely the Kohn-Sham method 1 in addition, it constitutes a solid support to reactivity models.2 DFT framework has been used to formalize empirical reactivity descriptors, such as electronegativity,3 hardness4 and electrophilicity index.5 The frontier orbital theory was generalized by the introduction of Fukui function,6 and new reactivity parameters have also been proposed.7,8 Moreover, relationships between those parameters have been found, and general methods to relate new quantities exist.9... 

The concept of selective sequestration of non-product species was first demonstrated using solid-supported scavengers with electrophilic and nucleophilic character in amine acylation, amine alkylation, and reductive amination protocols [46]. Since then, a wide range of scavenger reagents has become commercially available from various suppliers. The structures and functions of these scavenger resins are shown in Table 1. 

Recent example of cross-coupling reactions of organozinc halides with solid-supported electrophiles Oates L. J., Jack-son R. F. W., Block M. H., Org. Biomol. Chem. 1, 140-144 (2003). 

To install the appropriate functionality at C2, solution phase chemistry has relied on a trans-diaxial addition of an iodonium electrophile in the presence of an amine to form an iodosulfonamide. Displacement of iodine proceeds presumably through an aziridine intermediate and may be induced by a thiolate nucleophile to fashion thioethyl 2-amidoglycosyl donors [38]. Successful transfer of this method to the solid support allowed polymer-bound glycals to be converted into thioethyl gly-cosyl donors. These donors were in turn coupled with a variety of glycosyl acceptors, including glycals [39]. 

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