Orthogonal reactivity

Keywords Cyclopeptides Depsipeptides Peptoids Macrocycles Diketopiper-azines Benzodiazepines Ugi-reaction Polycyclic compounds Orthogonal reactivity Sequential reactions Iteration Bifunctional building blocks Medium sized rings Beta-turn motif... 

The orthogonal reactivities exhibited by IBr (2.5equiv at —78°C) and Au(PPh3)BF4 (5mol% at 0°C) in the activation of the alkene and alkyne groups of trichloroacetimidate 440 could be utilized in regioselective cyclizations toward 5,6-dihydro-4//-l,3-oxazine derivatives 441 or 442, respectively (Scheme 84) <2006OL3537>. 

The presence of orthogonal reactive groups in the product of the primary MCR (which is either formed during the primary MCR or present in one of the inputs) allows the union with the secondary MCR [17,99]. By varying the secondary MCR (e.g., by addition of inputs E/F or G/H), diverse (and complex) scaffolds will be available, making this strategy excellent for application in DOS. 

In 2009, our group demonstrated that the MCR strategy can also be used to obtain complexity as well as scaffold diversity (Scheme 17) [103]. The strategy is based on the abovementioned 3CR to 2//-2-imidazolines (reacting an isocyano ester, aldehyde or ketone and an amine) that shows extraordinary FG and solvent compatibility [96]. By incorporation of a second orthogonally reactive group in one of the starting materials, this MCR can be coupled to a second MCR. 

These considerations form the basis for the numerous techniques that are now available for the chemical modification of proteins. The sections that follow will examine these techniques and the reactive principles by which they function. A section describing reactions that display orthogonal reactivity to native protein functional groups has also been included because of the growing importance of these reactions as tools to label proteins in complex mixtures. Because it is not practical to summarize all protein bioconjugation methods here, this information instead is intended to serve as an introduction to the concepts that drive the development of these reactions. Several additional reviews and books on protein modification have been listed in the Further Reading section. 

Think Negative - Orthogonal Reactivity of Perfluoroaromatic and Perfluoroolefinic Systems... 

Scheme 2.34 Orthogonal reactivity of benzene and hexafluorobenzene toward electrophiles and nucleophiles, respectively.

For a recent study on orthogonal reactivity between organotrifluoro borate and trialkyl borate, see Molander,... 

The allyl-transfer method was extended to functionalised disilane 21.42," which represents a potentially bisallylic system with an orthogonal reactivity of the two moieties (Scheme 21.5). Indeed, allylation of a variety of aromatic and a,p-unsaturated aldehydes 21.4 with the latter reagent, catalysed by METHOX (21.26) and QUINOX (21.27), afforded the expected homoallylic alcohol 21.44 in high stereocontrol (<97% enantiomeric excess and >99 1 dr). However, the reaction takes 7-10 days, which is less than practical. 

The scheme PI 1.4.1, outlined below for the simultaneous cationic ROP and controlled free radical polymerizations, is based on the methods that were rst used and experimentally veri ed by Weimer et al. (1998). A multifunctional initiator, such as (P4-I), containing orthogonal reactive sites for CRP and ROP is used This alkoxyamine adduct, namely, benzoic acid 2-(4-chloromethyl)phenyl)-2-(2,2,6,6-tetramethyl piperidin-1-yloxy) ethyl ester, can be prepared (Puts and Sogah, 1997) by heating a solution of benzoyl peroxide and TEMPO in 4-vinylbenzyl chloride at 80°C for 24 h, followed by puri cation by chromatography. 

Figure 11.11 A multifunctional reagent containing orthogonal reactive sites for controlled free-radical, anionic, and cationic polymerizations. (From Puts and Sogah, 1997. With pemiission from American Chemical Society.)...

Though typically a stepwise procedure was used in which the azide-terminatred polymer was isolated and puri ed before reaction with the alkyne species, an in-situ end group transformation process was also condncted in both the cases in which the azide-terminated polymers were reacted in situ with alkyne-functionahzed methacrylates. This one-pot synthesis is possible due to the orthogonal reactivity inherent in chck chemistry. 

Shin, K. Ryu, J. Chang, S. Orthogonal reactivity of acyl azides in C—H activation Dichotomy between C—C and C—N amidations based on catalyst systems. Org. Lett. 2014, 16, 2022-2025. 

Figure 8 Strategies for synthesizing block copolymere displaying bioactive epitopes, (a) Sequential polymerization of monomers bearing a bioactive epitope, (b) PPM of two orthogonally reactive blocks.

Multifunctional surfaces can be prepared by a sequential functionalization of orthogonal reactive groups that are immobilized on a surface. For example, the... 

When choosing the right orthogonal reactive groups for a surface functionalization, self-sorting conditions of click reactions can be achieved [47]. 

Post-polymerization modification of reactive polymer films provides the possibility to design complex coatings associated with intricate structure and morphology [1, 4, 97, 98]. Using a simple procedure, two or more types of chemical functionalities can be applied onto substrates that are contained in covalently grafted polymer films. Multifunctional surfaces can be fabricated by sequential click reactions or simultaneous multiple click reactions in one-pot. Click-like reactions such as thiol-based additions, activated ester coupling, and azide-alkyne cycloadditions are those most used for post-polymerization modification, because these reactions yield orthogonal reactive polymer brushes rapidly and quantitatively [17]. 

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