Sequential chain extension

Sequential Chain Extension. The general synthetic approach adopted in our published work was to employ sequential chain extension reactions rather than block synthesis. Since two of... 

Figure 1. Synthesis of a chemical repeating unit of the Shigella flexneri variant Y O-antigen, employing a sequential chain extension strategy.

Benzoyl triflate prepared from TfOH and Benzoyl Chloride is a mild and effective benzoylating agent for sterically hindered alcohols and acylative ring expansion reactions. The applications of TfOH in Koch-Haaf carboxylation, Fries rearrangement, and sequential chain extension in carbohydrates are also documented. Recent applications of TfOH in cyclization reactions have been published. ... 

The main industrial use of alkyl peroxyesters is in the initiation of free-radical chain reactions, primarily for vinyl monomer polymerizations. Decomposition of unsymmetrical diperoxyesters, in which the two peroxyester functions decompose at different rates, results in the formation of polymers of enhanced molecular weights, presumably due to chain extension by sequential initiation (204). 

Addition polymers, which are also known as chain growth polymers, make up the bulk of polymers that we encounter in everyday life. This class includes polyethylene, polypropylene, polystyrene, and polyvinyl chloride. Addition polymers are created by the sequential addition of monomers to an active site, as shown schematically in Fig. 1.7 for polyethylene. In this example, an unpaired electron, which forms the active site at the growing end of the chain, attacks the double bond of an adjacent ethylene monomer. The ethylene unit is added to the end of the chain and a free radical is regenerated. Under the right conditions, chain extension will proceed via hundreds of such steps until the supply of monomers is exhausted, the free radical is transferred to another chain, or the active site is quenched. The products of addition polymerization can have a wide range of molecular weights, the distribution of which depends on the relative rates of chain grcnvth, chain transfer, and chain termination. 

Scheme 3 illustrates retrosynthetic analysis of the E and F series of PGs. The widely used Corey synthesis (2) takes notice of the presence of the two olefinic bonds in the side chains of PGF2a. The actual synthesis consists of a two-fold Wittig-type chain extension of a chiral dialdehyde equivalent with four defined stereogenic centers derived from cyclopentadiene via a series of bicyclic intermediates. A similar sequential synthesis has been developed at Upjohn Co. (la). These chemical syntheses are much more economical than enzymatic methods and are used for commercial synthesis of certain PGs. An alternative pathway pioneered by Sih is the conjugate addition approach (3). Nucleophilic addition of an E-olefinic co side-chain unit to a cyclopentenone in which the a side chain is already installed leads directly to PGE-type compounds. Untch and Stork used an co chain unit with a Z-olefinic bond (4). The most direct and flexible synthesis is the convergent three-component coupling synthesis via consecutive linking of the two side chains to unsubstituted 4-hydroxy-2-cyclopentenone derivatives (5, 6). 

Dienes or polyenes with a single methylene between two sequential (Z)-double bonds (so-called skipped methylene polyenes) represent a ubiquitous motif in nature, being found in fatty acids and numerous fatty acid derivatives. If the double-bond placement is correct, they can be synthesized from the appropriate fatty acids in a few steps by chain extension... 

Similar applications of acetylene chemistry appear equally promising, but have been less intensively studied. In an early contribution to this subject, Islam and Raphael observed that the product of sequential acetylation and Mannich chain extension of cyclopentylethynyl alcohol did undergo cyclization when heated in a mixture of formic and phosphoric acids, although in low yield (7 %).49 Greater... 

Chain termination probabilities initially decrease with increasing chain size (Fig. 2b) product distributions are non-Flory on all catalysts. This reflects an increase in readsorption rate as larger a-olefins become increasingly difficult to remove from liquid-filled catalyst pellets (4,5,14,40,41,44). Large olefins readsorb extensively and leave catalyst pellets predominantly after they form n-paraffins in sequential chain initiation and termination steps. As larger olefins (n > 30) disappear from the products, the chain termination probability reaches a constant value and product distributions become predominantly paraffinic and obey Flory kinetics (Fig. 2b). The asymptotic termination probability (/3=o) reflects the intrinsic probability of... 

Tandem chain extension at both the 1-alkyne and propargylic positions of 1-alkynes by sequential (1) alkylation and (2) hydroxy-alkylation (1,2-addition) of 1,3-dilithiated alkynes provides an attractive, one-pot preparation of functionally disubstituted alkynes. The required 1,3-dilithiated species are obtained by lithiation of 1-alkynes at both the 1- and 3- positions with two equivalents of n-BuLi in the presence of TMEDA (tetramethylethylenediamine). The two-stage chain extension depicted below for propyne involves initial alkylation of the dilithiated propyne with the less reactive electrophile, n-BuBr, at the more nucleophilic propargylic position. Subsequent hydroxyalkylation at the less nucleophilic alkynylide position with the more electrophilic formaldehyde furnishes the a-hydroxyalkyne. ... 

Block copolymers with hydroxyl segments were prepared by various ways An example utilizes the copper-catalyzed sequential copolymerizations of nBA and 2-[(trimethylsilyl)oxy]ethyl acrylate by the macroinitiator method into B-31 to B-33. The copolymers were then hydrolyzed into amphiphilic forms by deprotection of the silyl groups.313 A direct chain-extension reaction of polystyrene and PMMA with HEMA also afforded similar block copolymers with hydroxyl segments (B-34 and B-35).241-243 In block polymer B-36, a hydroxy-functionalized acrylamide provides a hydrophilic segment.117 Block copolymers of styrene and p-acetoxystyrene (B-37 to B-39), prepared by iron... 

The biosynthesis of the proanthocyanidins is believed to proceed by addition of an electrophilic extension unit derived from a flavan-3,4-dioP or a flavan-3-oP to a nucleophilic starter unit, most likely a flavan-3-ol, with sequential addition of further chain-extension units. Although the genetics of interflavanyl bond formation in the proanthocyanidin polymerization process are not yet defmed, " the search for the elusive condensing enzyme continues unabated. ... 

To further demonstrate the livingness of the process a chain extension of PNIPAAm was carried out. The initial block was obtained by using a ratio [M]o/[BIBA]o/[CuCl]o/[CuCl2]o/[Me6TREN]o of 120/1/1.6/0.4/2 with a NIPAAm concentration of 0.5 M. Then the block copolymer was synthesized by sequential addition after 38 min of a degassed aqueous solution of monomer (0.5 M) without purification of the macro-initiator. A CuCl-based catalyst was chosen to perform the reaction to avoid any termination. Indeed, in water, bromide-terminated polymers can be sensitive to halogen abstraction by nucleophilic substitution. Then with CuCl the resulting polymer-halide bound C-... 

Hydroxypentenylation. Sequential delivery of two substituents from Si to an acetal function accomplishes this chain extension. 

A new method for the conversion of aldopyranosides to 5-thioaldopyranosides is exemplified in Scheme 3 the isomeric acyclic intermediates, e.g. compound 33, could be separated, inverted at C-5 and cyclized stereoselectively, thus offering access to several different products. 5-Thio-D-arabinose (34) has been synthesized from D-arabinose in six standard reaction steps. Synthesis of 5-thio-L-fucopyranose, as the tetraacetate 35, from D-arabinose required chain-extension at the non reducing end which was achieved by diastereoselective reaction of aldehyde 36 with methyl lithium the D-aftro-product 37 was then treated sequentially with tosyl chloride and potassium thioacetate. A number of aryl a-5-thiofucosides, as well as p-nitrophenyl a-l,5-dithiofucoside, were prepared from 1-acetate 35 directly or via a trichloroacetimidate. These compounds were used to demonstrate the importance of sulfur in the ring and oxygen at the... 

These materials have been synthesized by the sequential addition of reactants or by the chemical modification of chain ends to produce end-functionalized polymers which can be used in other chain extension reactions such as step addition or step condensation polymerization processes. 

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