Side-chain manipulation

Other exploits have focused on the electronic manipulation of the PPEs via side chains (Table 4, entries 7-16) [36]. If a conjugated side chain is utilized, then the electronic properties of the resulting PPE are influenced. The synthesis of such cross-conjugated PPE-PPV derivatives involves the Pd-catalyzed coupling of a diethynylbenzene derivative with a l,4-distyryl-2,5-diiodoben-zene. The electronic properties of such PPEs are variable by changing the styryl side chain (Table 4, entries 7-12). The polymers are attractive as active layers in light-emitting diodes (LEDs) and thin-film transistors. 

Pinto MR, Reynolds JR, Schanze KS, (2002) Polym Prepr 43 139-140 Pinto MR, Kristal BM, Schanze KS (2003) Langmuir 19 6523-6533. 

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Wu and co-workers (Wu et al., 1999) have demonstrated a novel chiral lactone enolate-imine process to access 2-azetidinone diols such as 35 (Scheme 13.10). Treatment of 34 with LDA at — 25°C in THF followed by addition of imine 3, afforded only trace product. Addition of HMPA or the less toxic DMPU during the lithium enolate formation step improved the yield and the trans cis diastereoselectivity ( 90 10). Recrystallization improved the purity to >95 5 trans cis 2-azetidinone. Addition of an equivalent of lithium bromide accelerates the rate of ring closure, presumably by destabilizing the intermediate lithium aggregates. Side-chain manipulation of 35 was accomplished by sodium... 

Side-Chain Manipulation with a Purine Derivative Unexpected... 

This contribution describes the chemistry and uses of the poly(aryleneethynylene)s (PAEs). The different types of syntheses for PAEs are described first and the most important classes of PAEs are highlighted. Their properties and uses are outlined. Polymer analogous reactions of poly(paraphenyleneethynylene)s (PPEs), i.e., hydrogenation, complexation with suitable organotransition metal fragments, and side chain manipulation are discussed with regard to the synthetic processes and the properties of the formed novel polymeric materials. 

PPEs should be amenable to postfunctionaUzation schemes. Side chain manipulation of PPEs has been discussed for the case of grafted polymers. Nuyken [126] has shown that a benzylic bromide-functionalized PPE is easily made by the polymer analogous conversion of a benzylic alcohol. This polymer is poised to react with any nucleophile to give side chain functionalized PPEs. Postfunctionalization schemes furnished biotinylated or mannosylated PPEs are useful in sensory schemes (vide infi a) [27,127-131]. 

Additional side-chain manipulations of 12 eventually furnished isolaurepinnacin 3. Similarly, Murai et al. s synthesis of (+)-obtusenyne 1 has demonstrated that a combination of Et2NH2Cl and Ti(0/-Pr)4 effected the stereospecific opening of epoxide 13 to afford chlorohydrin 14 with moderate regioselectivity (4 1), a pivotal intermediate used for the completion of the total synthesis of the target natural product." ... 

AH cephalosporins found in nature (Tables 1 and 2) have the D-a-aminoadipic acid 7-acyl side chain (21). AH of these compounds can be classified as having rather low specific activity. A substantial amount of the early work in the cephalosporin area was unsuccessfiiHy directed toward replacing the aminoadipic acid side chain or modifying it appropriately by fermentation or enzymatic processes (6,22). A milestone ia the development of cephalosporins occurred in 1960 with the discovery of a practical chemical process to remove the side chain to afford 7-ACA (1) (1). Several related processes were subsequendy developed (22,23). The ready avaHabHity of 7-ACA opened the way to thousands of new semisynthetic cephalosporins. The cephalosporin stmcture offers more opportunities for chemical modification than does that of penicillins There are two side chains that especiaHy lend themselves to chemical manipulation the 7-acylamino and 3-acetoxymethyl substituents. 

Standard retrosynthetic manipulation of PGA2 (1) converts it to 5 (see Scheme 2). A conspicuous feature of the five-membered ring of intermediate 5 is the /(-keto ester moiety. Retrosynthetic cleavage of the indicated bond in 5 furnishes triester 6 as a potential precursor. Under basic conditions and in the synthetic direction, a Dieck-mann condensation4 could accomplish the formation of a bond between carbon atoms 9 and 10 in 6 to give intermediate 5. The action of sodium hydroxide on intermediate 5 could then accomplish saponification of both methyl esters, decarboxylation, and epi-merization adjacent to the ketone carbonyl to establish the necessary, and thermodynamically most stable, trans relationship between the two unsaturated side-chain appendages. 

From 152, the synthesis of the tandem radical cyclization precursor 155 only requires a few manipulations of the two side chains. 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

A recent synthesis of the phenylisoserine side-chain of taxol is shown in Scheme 18. The enone 21 was obtained in high yield by condensation of benzal-dehyde with pinacolone. Employing the non-aqueous two-phase epoxidation protocol, epoxide 22 was obtained in 76% yield and 94% e.e. Recrystallisation of the epoxide furnished the desired enantiomer in 97 % e. e. Subsequent manipulations of the epoxy-ketone gave the taxol side-chain 23 with the required stereochemistry (Scheme 18). 

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