Double bonds multistep synthesis

In pharmaceutical appHcations, the selectivity of sodium borohydride is ideally suited for conversion of high value iatermediates, such as steroids (qv), ia multistep syntheses. It is used ia the manufacture of a broad spectmm of products such as analgesics, antiarthritics, antibiotics (qv), prostaglandins (qv), and central nervous system suppressants. Typical examples of commercial aldehyde reductions are found ia the manufacture of vitamin A (29) (see Vitamins) and dihydrostreptomycia (30). An acyl azide is reduced ia the synthesis of the antibiotic chloramphenicol (31) and a carbon—carbon double bond is reduced ia an iatermediate ia the manufacture of the analgesic Talwia (32). 

Double-bond isomerization was once used in the multistep synthesis of isoprene developed by Goodyear.266-268 2-Methyl-1-pentene produced by the dimerization of propylene was isomerized to 2-methyl-2-pentene over a silica-alumina catalyst at 100°C. The product was cracked to isoprene and methane. Because of the lower cost of isoprene isolated from naphtha or gas oil-cracking streams, synthetic isoprene processes presently are not practiced commercially. 

The polymerization of sucrose derivatives (esters, ethers, acetals) bearing a carbon-carbon double bond has been studied (Scheme 45). Polymers can be obtained by polymerization or copolymerization.146,404 414 The monomers are prepared either by multistep synthesis, leading to defined compounds and subsequently rather well-controlled polymerization processes,302,415,416 or by direct functionalization of unprotected sucrose, leading to mixtures of isomers and... 

As a consequence of the restricted jump-rope rotation around the trans double bond, (i j-cyclo-octene 38E is chiral. Optically active (E)-cyclo-octene has long been known, but the conventional multistep synthesis is rather tedious [138-140]. In contrast, direct-preparation of optically active (Ej-cyclo-octene through asymmetric photosensitization is an attractive alternative. The first enantiodifferentiating Z-E photoisomerization of cyclo-octene 38Z sensitized by simple chiral alkyl benzenecarboxylates was reported in 1978 to give low enantiomeric excesses (ee s) of <6% [141] a variety of systems and conditions have been examined since then to raise the product ee. For an efficient transfer of chiral information... 

A regioselective peroxidation by ra-chloroperbenzoic acid was accomplished during the multistep synthesis of alkaloids of pentacyclic Aspidosperma skeleton. By operating at low temperature, oxidation of the enamine double bond was effected more rapidly than that of the sulphoxide group and the epoxide intermediate was isolated49 (Scheme 33). 

Another rapidly progressing field is that of multistep reactions which occur in ordered sequences chemo-, regio- and stereo-selectively on a transition metal species. To this end, it is necessary to delay release of the desired product until the whole series of steps has been completed competitive terminations (such as hydride elimination) must be prevented or must only occur at low rates compared to the main sequence. An example, reported by Chiusoli in the late 50s, is offered by the nickel-catalyzed synthesis of methyl 2,5-heptadienoate from 2-butenyl chloride, acetylene, CO and methanol. The reaction is chemo-, regio- and stereo-selective the four molecules react in the order shown in Equation A3.4 (chemoselectivity) the butenyl group attacks the terminal allylic carbon rather than the internal one (regioselectivity) and acetylene insertion leads to a Z double bond (stereoselectivity). 

The first total syntheses of racemic zearalenone (rac-479) were reported in the 1960s by the Merck and Syntex research groups (364, 365). In their multistep synthesis routes of the seco acid, the double bond was introduced by a Wittig reaction, but the required ( )-configured double bond was not formed selectively and the yields of the following lactonization were very low. The yields of macrolactonization were improved remarkably by Corey (360) and Masamune (361) using new activation methods for carboxylic acids (366). In aU the syntheses of zearalenone, the macrolide was formed by lactonization, but numerous possibilities are evident for the cyclization step. Figure 9.4 illustrates some different approaches to the synthesis of zearalenone (367). 

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