Oxidative reactions, synthesis conjugates

Taylor s group also showed that the Horner-Wadsworth-Emmons (HWE)/conjugate-addi-tion sequence can be an efficient alternative to the thioetherification-oxidation reactions for the preparation of the required sulfones [59]. This was illustrated in the synthesis of the /3-(1 6)-mannofuranose-a-Glu C-dimer [60] (O Scheme 21). 

The use of these materials in a range of reactions [isomerization of alkenes and alkynes, C—C bond formation, aldol condensation, Knoevenagel condensation, nitroaldol reactions, Michael addition, conjugate addition of alcohols, nucleophilic addition of phenylacetylene, nucleophilic ring opening of epoxides, oxidation reactions, Si—C bond formation, Pudovik reaction (P—C bond formation) and synthesis ofheterocycles] have been discussed in detail by Ono [248], as well as in the other cited reviews. We will thus discuss here only selected examples. 

Fig. 1. Diagram of the metabolic reactions that determine pool size of the free lAA in plant cells. Inputs include (A) de novo synthesis from non-tryptophan and tryptophan pathways (B) conjugate hydrolysis and (C) transport. Outputs from the lAA pool inelude (D) oxidative catabolism (E) conjugate synthesis (F) transport and (G) possible lAA use during growth and developmental processes.

Glucosamine-derived imines 58 were used for the synthesis of carbapenem and carbacephem antibiotics. [2 + 2] Cycloaddition with methoxyacetyl chloride provided diastereomeric S-lactams with low asymmetric induction [56]. Radical cyclization and oxidation reactions of diastereoisomer 59 led to car-bapenems 60 and 61 (Scheme 16) [57]. The same research group continued the transformation of S-lactams derived from o-glucosamine. In particular, a tandem ehmination-conjugate addition performed on 62 provided the second ring of the carbacephem, for example 63 (Scheme 17) [58]. 

Rosini and co-workers reported the synthesis of 5-acyl-3-(ethoxycarbonyl)-2-isoxazoline-2-oxide 163, via conjugate addition of ethyl nitroacetate 161 to the a-bromo enones 160 followed by ring closure (Scheme 42) [143]. The reaction was performed under both homogeneous and heterogeneous conditions, but the former was found to be superior in terms of the isolated yield of the product. 

Caution may be required in oxidation reactions. Ceric salts, for example, can alter or destroy products. Ferric salts seem to be more active in 1 N hydrochloric acid solution (P. Schudel, personal communication), but the acidic conditions may affect products such as enol ethers. Temperatures also seem to be important in some cases. For example, a substituted cyclohexa-diene complex was unaffected by CuClj at —20°, but it was converted into the free conjugated diene (mainly) at 0° and into the unconjugated diene and substituted benzene derivative at +20° (A. J. Birch and C. Sell, unpublished). In other cases, e.g., arylmanganese derivatives, although interesting synthetic reactions occur, the metal is not so readily removed. This general area is clearly one for further research if useful application is to be made in organic synthesis. 

Other Oxidation Reactions. Ag20 oxidizes aldehydes to acids, and conjugated keto aldehydes to conjugated keto acids. For example, Ag20 was used to selectively oxidize one of two formyl substituents of an intermediate in the total synthesis of inhibitor K-76 (eq 8). The unreactive formyl substituent is conjugated with the hydroxyl and alkoxy substituents. 

Remote Oxidation.—Remote oxidation reactions generally involve intramolecular hydrogen abstraction. The best known example is the Barton reaction (photolysis of nitrite esters). "- One of the most important applications of this reaction was to the synthesis of aldosterone acetate. The yield of this reaction has been substantially improved (55%) by irradiating the dienone nitrite ester (172) in which the extended conjugation ensures that sufficient separation between C-19 and the 11/3-oxygen atom exists to suppress functionalization at C-19 in favour of attack at C-18. Another recent application of the Barton reaction occurred in the synthesis of perhydrohistrionicotoxin (175), where the key step was the stereoselective formation of the oxime (174) from the nitrite ester (173). °... 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

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