Tether Subject

Highly branched polymers, polymer adsorption and the mesophases of block copolymers may seem weakly connected subjects. However, in this review we bring out some important common features related to the tethering experienced by the polymer chains in all of these structures. Tethered polymer chains, in our parlance, are chains attached to a point, a line, a surface or an interface by their ends. In this view, one may think of the arms of a star polymer as chains tethered to a point [1], or of polymerized macromonomers as chains tethered to a line [2-4]. Adsorption or grafting of end-functionalized polymers to a surface exemplifies a tethered surface layer [5] (a polymer brush ), whereas block copolymers straddling phase boundaries give rise to chains tethered to an interface [6],... 

The Alexander model and its descendants impose strong restrictions on the allowed chain configurations within the tethered assembly. The equilibrium state thus found is subject to constraints and may not attain the true minimum free energy of the constraint-free system. In particular, the Alexander model constrains the segment density to be uniform and all the chain ends to be at the same distance from the grafting surface. Related treatments of curved systems retain only the second... 

Vinyl cyclopropanes tethered to an aUcyne chain 127 were also subjected to the cycloisomerisation reaction in presence of the NHC-Ni catalyst system (Scheme 5.34) [39], The product formation depends on the substrate used and the NHC hgand. When SIPr carbene is used, three different products were obtained depending on the size of the R group attached to the alkyne moiety. If R is small (like a methyl) product 128 is obtained exclusively. If R is Et or Pr a mixture of 128 and 129 is obtained in 3 2 to 1 2 ratio, respectively. However, when R is large groups such as Bu or TMS only product 130 is obtained. When IfBu carbene 131 is used as the ligand, cycloisomerisation of 127 afforded product 128 exclusively, regardless of substituent size (Scheme 5.34) [39]. 

Inter- and intramolecular hetero-Diels-Alder cycloaddition reactions in a series of functionalized 2-(lH)-pyrazinones have been studied in detail by the groups of Van der Eycken and Kappe (Scheme 6.95) [195-197]. In the intramolecular series, cycloaddition of alkenyl-tethered 2-(lH)-pyrazinones required 1-2 days under conventional thermal conditions involving chlorobenzene as solvent under reflux conditions (132 °C). Switching to 1,2-dichloroethane doped with the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) and sealed-vessel microwave technology, the same transformations were completed within 8-18 min at a reaction temperature of 190 °C (Scheme 6.95 a) [195]. Without isolating the primary imidoyl chloride cycloadducts, rapid hydrolysis was achieved by the addition of small amounts of water and subjecting the reaction mixture to further microwave irradia-... 

UCW = capped water, TW = tethered water (see text), k = force constant for restraining potential (kcal/mol/A2). b Radius (A) of solvation sphere. 1 Numbers of dynamical water molecules within solvation sphere. d Mean and standard error for the forward (i.e. 8-methyl-N5-deazapterin —> 8-methylpterin) and reverse mutation of the electrostatic force field Cutoff for protein-ligand and solvent-ligand interaction all other interactions are subject to a 9 A cutoff. 

When 1,3-dienes containing a tethered alcohol are subjected to Wacker-type reactions, the initial intramolecular oxypalladation event creates a 7r-allylpalladium species, which can then undergo an additional bond-forming process to effect an overall 1,4-difunctionalization of the diene with either cis- or // -stereochemistry (Scheme 18).399 An array of substrate types has been shown to participate in this reaction to generate both five- and six-membered fused or ro-oxacycles.435-437 Employing chiral benzoquinone ligands, progress toward the development of an asymmetric variant of this reaction has also been recorded, albeit with only modest levels of enantioselectivity (up to 55% ee).438... 

In order to gain further insight into the reaction mechanism, the indicated oxygen-tethered keto-enone was subjected to basic hydrogenation conditions under 1 atmos. elemental deuterium. Deuterium incorporation is observed at the former enone / -position exclusively. In addition to mono-deuterated material (81% composition), doubly-deuterated (8% composition) and non-deuterated materials (11% composition) are observed. These data suggest reversible hydro-metallation in the case of keto-enone substrates. Consistent with the mechanism depicted in Scheme 22.4, deuterium is not incorporated at the a-position of the aldol product [24b] (Scheme 22.5). 

The presence of dangling segments in the IPN decreases the structural solidity of the system since steps associated with the tethered chains have a finite lifetime subject to the dynamics of the free end [5,6]. If i )j is the fraction of strands in the (i) network that are crosslinked on both ends, then ... 

Ester-tethered enyne systems cycloisomerized to give lactone products (Eq. 11) [24]. Eor example, enyne 6 reacted under the Alder-ene conditions of [Rh(COD)Cl]2/BlNAP/ AgSbEg to give the corresponding lactone (Eq. 11). Once again free hydroxyl groups on the allylic terminus were incorporated into the cyclization precursors and subjected to the Alder-ene conditions, which led to the exclusive formation of the tautomerized products in good yields and enantioselectivities (Eq. 12). 

Moreover, both the as- and trons-aUcenes react at the same rate and yield the same product (Tab. 8.9, entries 1 and 2). As demonstrated above, this was not the case with the N-tethered enynes (Tab. 8.2, entry 6) which gave a mixture of products. Nitrogen-and oxygen-tethered enynes were subjected to the rhodium(I) conditions affording high yields of the halogen shift product (Tab. 8.9, entries 1-10). 

In order for Ras to function properly, the protein must be localized to the plasma membrane. This is achieved by the addition of a farnesyl group to a cysteine residue near the carboxy terminus, which then acts as a tether to the cellular membrane. Farnesyl transferase, the enzyme that adds the farnesyl moiety to Ras, is also a target for small-molecule intervention. This class of inhibitors is the subject of another chapter (Angibaud et al, in this volume). 

In 1994, Diederich and co-workers reported a very important approach for the regioselective formation of multiple adducts of Cjq by tether-directed remote functionalization [75]. This technique allows for the synthesis offullerene derivatives with addition patterns that are difficult to obtain by thermodynamically or kinetically controlled reactions with free untethered addends. This important subject has been extensively reviewed [26, 76, 77]. 

The thermolytic preparation by De Shong et al. (74) of azomethine ylides from aziridines and their intermolecular reactions are the first examples of singly stabilized ylides of this type. However, the protocol has been further extended to include intramolecular processes. Aziridines tethered to both activated and unactivated alkenes were subjected to flash vacuum thermolysis generating cycloadducts in moderate-to-excellent yields. While previously singly activated alkenes had furnished low material yields via an intermolecular process, the intramolecular analogue represents a major improvement. Typically, treatment of 222 under standard conditions led to the formation of 223 in 80% yield as a single cis isomer. Similarly, the cis precursor furnished adduct 224 in 52% yield, although as a 1 1 diastereomeric mixture (Scheme 3.77). 

Pericas and Jeong demonstrated independently that sulfur-tethered substrates, when subjected to the PKR conditions, afforded the desired bicyclic products. The sulfur tether is removed cleanly by Pummerer reaction after oxidation of sulfur to sulfoxide or 1,4-addition of bisalkyl cuprate followed by hydrogenolysis of sulfide with Raney nickel. It is worth mentioning that the regioselectivity regarding the acetylene part is opposite to that of the intermolecular version (Equation (30)). 

A series of empirical schemes targeting the assembly of ternary complexes on beads have been attempted with varying degrees of success (reviewed in Simons et al, 2005). In Fig. 1, the molecular assemblies that are the subject of this chapter are based on the tethering of G protein heterotrimers to beads by an epitope tag (either hexahistidine or FLAGt ) fused to the N-terminus of the y subunit, and projected away from its binding partners in three-dimensional reconstructions. 

The intramolecular nitrogen-trapping protocol used by Banwell has also been successfully exploited in the assembly of spirocyclic frameworks relating to the aromatic erythrina alkaloids.24 However, when it was applied to the synthesis of nonaromatic spirocycles, as found in histrionicotoxin, the flexible alkyl tether proved to be problematic.25 In this study, gem-dichlorocyclopropane substrate 37 was initially subjected to silver(I) salts under a variety of conditions only to provide solvolysis and elimination products without any indication of trapping by the pendent... 

Now consider this same chain immersed in a melt of like chains all atoms are in thermal motion except the end atoms of the tethered chain, and in addition to the bonded interactions, all atom pairs are subjected to nonbonded interactions through u b, Eq. (5). 

Now, in addition to the forces from their bonded adjacent atoms, the end atoms are subject also to nonbonded interactions from those atoms in the surrounding melt as well as possibly those from other atoms in the chain. Again, it is necessary to apply external forces to the end atoms of the tethered chain to keep them in equilibrium. 

Palladium(II)-promoted oxidative cyclization of alkenes bearing tethered nucleophiles represents an intramolecular variant of the Wacker reaction. These reactions, which typically generate five- and six-membered heterocycles, have been the subject of considerable interest in organic chemistry [89-96]. Contemporary interest centers on the development of enantioselective examples [95,97] and reactions that employ dioxygen as the sole oxidant for the Pd catalyst [92-96]. 

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