Scavengers of nucleophiles

Maleimide is a well-known Michael acceptor, dienophile and dipolarophile and hence is another versatile functional moiety that has found multiple uses in combinatorial chemistry as both a scavenger as well as a template in library synthesis [15]. Barrett [16] and Porco [17] have both reported the synthesis of a polystyrene resin-supported maleimide but did not report its use in the scavenging of nucleophiles. Hall and coworkers have described the synthesis of a supported-maleimide... 

Silverman has pointed out that several criteria must be met to demonstrate that a compound is a true suicide substrate 1101 (1) Loss of enzyme activity must be time-dependent, and it must be first-order in [inactivator] at low concentrations and zero-order at higher concentrations (saturation kinetics), (2) substrate must protect the enzyme from inactivation (by blocking the active site), (3) the enzyme must be irreversibly inactivated and be shown to have a 11 stoichiometry of suicide substrate active site (dialysis of enzyme previously treated with radiolabeled suicide substrate must not release radiolabel into the buffer), (4) the enzyme must unmask the suicide substrate s potent electrophile via a catalytic step,1121 and (5) the enzyme must not be covalently labeled with the activated form of the suicide substrate following its escape from the active site (the presence of bulky scavenging thiol nucleophiles in the buffer must not decrease the observed rate of inactivation). 

Finally, highly reactive salts such as triphenylmethyl hexachloroantimonate provide very convenient scavenging agents for the removal of the last traces of nucleophilic impurities in polymerisation solvents. Penczek (35) has taken this further in developing a spectroscopic technique for the determination of trace quantities of residual water by reaction of the latter with known concentrations of triphenylmethyl salts, according to the following equilibria ... 

Various diazonium salts have been prepared using this approach55 and thermoanalytically characterized.56 Both the structure of the diazonium moiety and the counterion clearly influence the stability of the diazonium moiety. The thermally stable diazonium ion 71 (Z = Cl, Y = CH20) [ty2 (25°) > 100 days] is also capable of scavenging various nucleophiles (amines, phenols, and anilines).57 This resin with a tetrafluoroborate counterion (resin 66) is called T2 diazonium resin and it is now commercially available from Novabiochem. 

As to the next step, namely, the reaction of aryl radicals with nucleophiles, we should take into account the fact that air molecular orbital, which initially accommodates the incoming electron, is available in the aryl halide. The electron is subsequently transferred in-tramolecularly from the it to the o molecular orbital of the carbon-halogen bond. Aryl radicals effectively scavenge H atoms. Therefore, an abstraction of a hydrogen atom from the solvent may occur. However, in the case of nucleophiles that can act as effective traps of aryl radicals, the addition of a nucleophile to the phenyl radical takes place. At this point, let us focus on the step of addition of the nucleophile (Y ) to the intermediate radical (Ph). When a new a bond begins to form between the sp3 carbon-centered radical (H5C6) and... 

Discussion of the mechanism of photosubstitution in Cr(III) complexes has largely concerned the possibility of a seven-coordinate intermediate. Such an associative type mechanism is not proven by any means, but there is some circumstantial data to support it and some data that tends to rule out a purely dissociative mechanism involving the photoinduced formation of a discrete five-coordinate intermediate capable of being competitively scavenged by nucleophiles in the medium. 

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,... 

Taddei has developed a soluble PEG supported scavenger 53 to capture a variety of nucleophilic functional groups (Scheme 13) [21]. This scavenger was based on an electrophilic dichlorotriazine core and relied on selective precipitation (by the addition of ether to acetonitrile) to remove it from the reaction mixture. This scavenger 53 is particularly versatile, and has been used to remove primary, secondary and tertiary alcohols, diols and thiols... 

A similar scheme can be designed for PET processes via exdted electron donors. However, accroding to our knowledge, so far only reports on examples shown in Scheme 7 are known. Scavenging by nucleophiles (N) or electrophiles (E) proceeds according to equation 5 and 6 and should also depend on the degree of solvation of the ionic intermediates and competing processes as shown in Scheme 7. 

It should be noted that several groups have utilized the nucleophilic scavenging of radical cations by alcohols for synthetic processes [28, 61]. 

However, in most cases, the detailed mechanism is not yet known, i.e., whether CIP, SSIP or even free radical ions are scavenged by the nucleophile. Arnold and Snow [62] suggest an attack of methanol to solvated olefin radical cations, whereas Mariano observed a highly stereoselective example of a direct scavenging of a radical cation — radical anion pair by methanol [63]. Although this process has received relatively little attention, it is obvious that scavenging of different types of radical ion intermediates is not only possible but may be used to differentiate between the various types of radical ion pairs (CIP and SSIP). 

The ability of diazonium salts to act as radical scavengers for nucleophilic alkyl radicals was first discovered in mechanistic studies on the Meerwein arylation [96]. Shortly after, this concept was applied for the functionalization of a limited group of activated alkenes [97-99]. The much greater synthetic potential of this functionalization type, which arises from the successful use of non-activated alkenes as substrates, has recently been investigated. In a typical reaction, as illustrated in Scheme 19, the diazonium salt 48 acts as source for aryl radicals 49 and as radical scavenger [100]. 

Mechanism The bromonium ion intermediate is formed by the displacement of a Br by nucleophilic attack of a neighbouring bromine atom. The R2Te acts as a scavenger of the Br+ and alkene is formed as shown in Scheme 4.7. 

Additional tests such as the addition of nucleophilic scavengers (e.g., thiols such as dithiothreitol or j8-mercaptoethanol) can provide further evidence for the presence of a free, reactive electrophilic species. The scavengers should quench all of the free reactive species, thereby protecting the enzyme from inhibition. Unfortunately, this method cannot exclude the possibility that a nucleophilic thiol may even attack the bound reactive species at the active site of the enzyme (which would also give rise to protection from inactivation). However, the use of a bulky thiol, such as reduced glutathione, should limit that possibility. An alternative scenario occurs wherein the released reactive species returns and reacts faster with an active-site nucleophile than with the added thiol. Clearly this is a complex problem and, consequently,it is advisable to use several different tests to avoid misleading conclusions. 

A large variety of nucleophiles may be used as allyl group scavengers in the palladium-catalyzed deprotection of allylic derivatives, including oxygen, nitrogen, carbon, or sulfur nucleophiles, and hydride donors. 

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