Alcohols, oxidizing reagents formation

Our first task is to assemble 3-phenyl-1-propanol from the designated starting material benzyl alcohol. This requires formation of a primary alcohol with the original carbon chain extended by two carbons. The standard method for this transformation involves reaction of a Grignard reagent with ethylene oxide. 

The preparation of chiral dialkylazodicarboxylates and their use as electrophilic enolate animation reagents, were first reported in 1995 by Vederas and co-workers [51]. A series of chiral dialkyl (menthyl 97a, bomyl 97b, isobomyl 97c) azodicarboxylates were prepared by conversion of the corresponding alcohols into chloro-formates, condensation with hydrazine and oxidation with IV-bromosuccinimide and pyridine. Compounds 97 were obtained in 35-50% yield (Scheme 45). 

These reagent systems are very effective for the oxidation of primary and secondary alcohols, without the formation of any by-products. 

Polymer-supported triphenylphosphine ditriflate (37) has been prepared by treatment of polymer bound (polystyrene-2% divinylbenzene copolymer resin) triphenylphosphine oxide (36) with triflic anhydride in dichloromethane, the structure being confirmed by gel-phase 31P NMR [54, 55] (Scheme 7.12). This reagent is effective in various dehydration reactions such as ester (from primary and secondary alcohols) and amide formation in the presence of diisopropylethylamine as base, the polymer-supported triphenylphosphine oxide being recovered after the coupling reaction and reused. Interestingly, with amide formation, the reactive acyloxyphosphonium salt was preformed by addition of the carboxylic acid to 37 prior to addition of the corresponding amine. This order of addition ensured that the amine did not react competitively with 37 to form the unreactive polymer-sup-ported aminophosphonium triflate. 

Oxidation of an allylic alcohol. This reagent has been used successfully to oxidize the benzyl ester of the /S-lactam antibiotic clavulanic acid (1) to the labile allylic aldehyde 2. Attempted oxidation with the Pfitzner-Moffatt reagent resulted in formation of a 1,3-diene by a 1,4-elimination. ... 

Many methods have been developed for the oxidation of primary and secondary alcohols. Oxidation of secondary alcohols normally gives rise to ketone products, whereas primary alcohols form aldehydes or carboxylic acids, depending on the reagent and conditions. Selective oxidation reactions have been developed that give these different types of products, even in the presence of other sensitive functionality. This section will describe, in turn, the different reagents used for the formation of aldehydes and ketones, before discussing the formation of carboxylic acids. 

The synthesis of 188 from epoxide 189 was done as shown in Scheme 25. Epoxide opening with a propargyl alane reagent [124], protection-deprotection of the alcohol functions, and Redal reduction led to the -allylic alcohol 194, also obtained by another route [116]. Asymmetric epoxidation-Redal epoxide opening [60-62] followed by silylation and debenzylation led to intermediate triol 195. Selective six-membered acetal formation and primary alcohol oxidation then furnished building block 188. 

Chromium VI) reagents are powerful oxidants. The reaction of a secondary alcohol with chromium trioxide and acid in aqueous acetone is called Jones s oxidation, and the product is a ketone. Chromium oxidation of an alcohol proceeds by formation of a chromate ester, followed by loss of the a-hydrogen to form the C=0 unit. 

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