Unprotected functional groups

Radical polymerization is the most useful method for a large-scale preparation of various kinds of vinyl polymers. More than 70 % of vinyl polymers (i. e. more than 50 % of all plastics) are produced by the radical polymerization process industrially, because this method has a large number of advantages arising from the characteristics of intermediate free-radicals for vinyl polymer synthesis beyond ionic and coordination polymerizations, e.g., high polymerization and copolymerization reactivities of many varieties of vinyl monomers, especially of the monomers with polar and unprotected functional groups, a simple procedure for polymerizations, excellent reproducibility of the polymerization reaction due to tolerance to impurities, facile prediction of the polymerization reactions from the accumulated data of the elementary reaction mechanisms and of the monomer structure-reactivity relationships, utilization of water as a reaction medium, and so on. 

Free radical reactions are proving to be synthetically useful altern-atives for producing carbon-carbon bonds. Recently, Stork has shown that vinyl radicals are valuable in ring forming reactions since they place a double bond in a predictable position. Their compatibility with many unprotected functional groups and their ability to form quaternary centers are additional features which make vinyl radical cyclization an attractive synthetic method. 

Fig. 2.1 Divergent synthesis. C=coupling points F=active, unprotected functional group P= protected, inactive (protective group) functionality. The core of the dendri-...

It must be resistant to reagents that would attack the unprotected functional group. 

Functionalization of several pyranose sugar derivatives, e.g. 28, 30, 33, was achieved with a variant of this method in which 3-oxabicyclo[4.1.0]heptanyl radicals were generated, either photochemically from benzoate esters, or from bromides. These photochemical transformations left unprotected functional groups in the substrate intact, including bromomethyl, ester, and ether groups, and rather effectively demonstrated the tolerance of free-radical intermediates for such functionality. 

Kagan and co-workers pioneered the work on the reductive behavior of the low oxidation states of the lanthanide elements in organic synthesis [2b]. Ln metals and Ln(II) derivatives were subsequently found to promote a number of important individual reactions [301]. The combination of one- and two-electron chemistry sets Sml2 apart from virtually every other reductive coupling agent currently available and exhibits exceptional properties for sequential conversions tolerating unprotected functional groups [lb]. 

This method involves the use of functional initiators with a protected or unprotected functional group. When the functional group is unreactive under the polymerization conditions, protection is not necessary. Functional vinyl ethers have extensively been used in the Bving cationic polymerizations of vinyl ethers and these functional poly(vinyl ethers) can be derivatized to the desired functionahty by simple organic reactions. Vinyl ethers carrying a variety of functional pendant groups, in a general form (Scheme 26.1) ... 

Resistant to the reagents used to transform the unprotected functional group or groups. 

The critical feature of the NCL method is that ligation occurs at an N-terminal Cys residue, no matter how many additional internal Cys residues are present in either segment. Such fascinating chemoselectivity allows the use of unprotected functional groups present in either of the two reacting proteins. For detailed studies of the mechanism of the NCL reaction, the interested reader should consult the studies by Dawson et al. [31, 32]. Here it suffices to say that transesterification of esters into thioesters represents an energetically uphill process in view of the higher reactivity (lower stabihty) of the latter. It can be achieved if the subtle interplay between entropic and enthalpic factors favours the process, or if the product is present in a low steady-state concentration, and is consumed in the subsequent irreversible step, as for the NCL process shown in Scheme 12.2. 

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