Linear synthesis using coupling agents

Cationic synthesis of block copolymers with non-linear architectures has been reviewed recently [72]. These block copolymers have served as model materials for systematic studies on architecture/property relationships of macromolecules. (AB)n type star-block copolymers, where n represents the number of arms, have been prepared by the living cationic polymerization using three different methods (i) via multifunctional initiators, (ii) via multifunctional coupling agents, and (iii) via linking agents. 

There have been few alternative syntheses of bortezomib (1) published in the literature. A more convergent route was proposed by Ivanov et al. employing N-pyrazinyl-Z-phenylalanine (28) as a coupling partner to amino boronic ester 20.31 The use of TBTU as coupling agent was shown to suppress racemization in the reaction. Despite a convergent approach being considered by Millennium, the linear approach was ultimately adopted for synthesis on scale. 

A similar approach was used to construct a unique triblock copolymer having dendritic termini connected by linear segment. The synthesis of the dendritic-fe/oc/c-linear-fetocA -dendritic PS, referred to as the pom-pom structure due to its dumbbell-like shape, results from a convergent anionic polymerization procedure using dichlorodimethyl-silane as a coupling agent [119]. 

Gao and Matyjaszewski carried out the rst synthesis of PSt star polymers using a combination of ATRP and click chemistry (Gao and Matyjaszewskki, 2006). PSt linear chains with high azide chain-end functionality were prepared and coupled with tri- and tetra-alkyne-containing coupling agents under mild conditions to produce PSt 3-arm and 4-arm polymers, respectively (Scheme P12.6.1). 

Another potential problem with DCC is that at the completion of the reaction some DCU remains in solution with the product, necessitating additional purification. Water-soluble carbodiimide derivatives such as l-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide Metho-p-toluenesulffonate and l-Ethyl-3-(3 -dimethylaminopropyl)carbodiimide Hydrochloride (EDCI) obviate this problem, as they are removed by a simple extraction. Many newer coupling agents have been developed for peptide synthesis and other acylation reactions. These include Benzotriazol-l-yloxytris(dimethylamino)phosphonium Hexafluorophosphate (BOP)," 0-Benzotriazol-l-yl-N,N,N, N -tetramethyluronium Hexafluorophosphate (HBTU)," Bis(2-oxo-3-oxazolidinyl)phosphinic Chloride (BOP-Cl), and (1 //-1,2,3-benzotriazol-1 -yloxy)tris(pyrTolidino)phosphonium hexafluorophosphate (PyBOP). In addition to linear and polymeric amides, lactams of various ring sizes have been synthesized using these methods (eq 1)."... 

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