Activation-substitution coupling

G. Yang, F. Kong, and R. R. Fraser, Synthesis, conformational analysis and glycosidic coupling reactions of highly active substituted 2,7-dioxabicyclo[4.1.0]heptanes 1,2-anhydro-3,4-di-0-benzyl-u-D-xylopyranose, Carbohydr. Res., 258 (1994) 49-58. 

Keywords Allylic substitution CH activation Cross-coupling Cycloisomerization Domino reactions Metallation Multicomponent reactions Palladium catalysis... 

Approaches to the synthesis of peptoids are summarized in Scheme 21. In the original method, Simon et al. [55] reported a monomer approach analogous to peptide synthesis in which the appropriate Fmoc-protected N-substituted glycines (84) were activated and coupled to the secondary amino group of the resin-bound peptoid chain to yield 85 (Scheme 21). Several synthetic routes to A-Fmoc-protected precursors (84) that were utilized in this early work are summarized in Scheme 22. 

Phosphodiesteric/peptidic/glycosidic bond formation (coupling reaction) is a nucleophilic substitution reaction of a hydroxy/amino/hydroxy group at a phosphoesteric/carboxyl/ acetal group, resulting in dehydration. The coupling reaction can be conducted in two procedures activation-substitution (via stable activated intermediate) and direct condensation... 

Activation-substitution. To promote coupling of biomonomers via a nucleophilic substitution, which has to be performed under mild conditions, the electrophilic (esteric/carboxylic/acetal) site is activated to increase its electrophilicity. This is achieved by an introduction of electron-withdrawing moieties (decrease the electron density at the electrophilic site), thereby favoring the subsequent nucleophilic attack. Some of the common activated structures are illustrated in Table 8.6. 

Various situations are analyzed where the two metal centers play a role in one of the coordination modes A-E. There are many cases in which bimetallic catalysis can occur with the two metals acting cooperatively, for instance, in the dimerization of alkynes at two ruthenium metal centers, where a ruthenium-vinylidene species is formed, which is able to subsequently activate the second alkyne reactant through a C-H cleavage on the second ruthenium center. The coupling of these two moieties occurs on this dinuclear platform to provide the enyne product molecule. Examples are also presented where bimetallic catalysts cooperatively activate substituted alkynes in the catalyzed formation of heterocycles. 

The most diffused actuating configuration, in which these materials are used, is represented by the so-called unimorph bilayer bender. This kind of actuator consists of a film of active material coupled to a passive supporting layer. The bilayer structure is operated within an electrochemical cell, having a liquid electrolyte in which the device is immersed. The active polymeric layer of the actuator works as one electrode of the cell, while a counter electrode and a third reference electrode are separately immersed in the electrolyte. One end of the bilayer is constrained, while the other is free. The potential difference applied between the electrodes causes red-ox reactions of the conducting polymer. Since the CP and the passive layers are mechanically interlocked, when the polymer swells/shrinks the passive layer, which can not modify its dimensions, transforms the CP linear displacement into a bending movement of the structure [238-242]. Very similar is the bimorph structure. In this case the passive layer is substituted by a second CP film and they work in opposition of phase. 

The use of the azo-linking group (-N = N -) in liquid crystal chemistry is now well documented, and hundreds of compounds of this class have been cited in the chemical literature [47] the linkage is formed by an azo coupling reaction between a substituted aryl diazonium salt and a suitably activated substituted benzenoid compound [50]. 

C-H activation is an important and rapidly developing area of dendralene synthesis. In very recent years, several C2-C3 bond forming approaches to dendralenes involving C-H activation have been reported. In 2013, Glorius and coworkers developed a Rh(III)-catalyzed, Heck-type alkenyl C-H activation and coupling reaction with allenyl carbinol carbonates 205 and acrylamides 206 (Scheme 1.33) [157]. This new reaction performs well for the synthesis of highly substituted [3]dendralenes. 

A similar transformation was subsequently reported in 2014 by Fu and coworkers, who used allene and carbamate precursors to generate [3] dendralenes via rhodium(III) catalysis (Scheme 1.34) [158]. A variety of different carbamates 213 successfully rmderwent Rh(III)-catalyzed C-H activation and coupling to generate cychc and acyclic substituted [3] dendralenes 214. While the general route works quite well between the tri-substituted allene and acyclic carbamates, the reaction is not high yielding if the enol ester is cychc or the allene is mono- or tetra-substituted. 

When the pressure is low and mixture conditions are far from critical, activity coefficients are essentially independent of pressure. For such conditions it is common practice to set P = P in Equations (18) and (19). Coupled with the assumption that v = v, substitution gives the familiar equation... 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

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