Ethers to esters and lactones

Despite these early successes, few synthetic chemists appeared to recognize the potential of metallic oxidants for the oxidation of ethers to esters and lactones, and only a few further developments were published prior to 1980. Since that time, as the chemistry of these reagents has become better understood, their use has increased dramatically to the stage where they are now the reagents of choice for many applications, including complex natural product synthesis. 

Traws-RuCljCdppp) (dppp=(l,2-diphenylphosphino)propane, sometimes abbreviated as (dpp) in the literature) is made from K2[Ru(H30)Cl5] and (dppp) in refluxing EtOH. Oxidation of a wide range of ethers to esters or lactones was effected by franx-RuCl Cdppp) or [RuCl(dppp)2]Vaq. Li(C10)/CH3Cl2 (Table 5.2) [931]. 

Abstract This chapter principally concerns oxidations of organic substrates containing N, O, S, P, As and Sb. Oxidations of amines are covered first, including primary amines to nitriles or amides secondary amines to imines or other products tertiary amines to N-oxides or other prodncts (Section 5.1) and the oxidation of amides (5.2). Oxidation of ethers to esters or lactones follows (5.3), then of sulfides to sulfoxides or sulfones (5.4) and of phosphines, arsine and stibines to their oxides (5.5). A final section (5.6) concerns such miscellaneous oxidations not covered by other sections in the book. 

Table 5.2 Oxidation of ethers to esters or lactones and suMdes to sulfoxides or sulfones... 

Simple mono- or di-substituted enol ethers may be oxidized to esters and lactones (Table 8, entries 1 and 2). However, fully substituted enol ethers undergo oxidative cleavage, since the proposed mechanism for oxidation to an ester involves a hydride shift which can no longer take place. 

Both enol esters and enol ethers (vinylogous esters) undergo similar intramolecular photocycloaddtions, but enol esters have advantage over enol ethers in terms of fragmentation process. Fragmentation of the cyclobutane photoadducts from enol esters is conveniently carried out under basic conditions, whereas that from enol ethers often requires additional operation to convert ether to ester or lactone (vide infra). For this reason, enol esters are more widely used than enol ethers. 

The Tebbe reaction, which converts the oxo groups of esters and lactones to methylene groups to give enol ethers, is described in section 2.1.2. 

Halogens are frequently used as oxidation agents and, under two-phase conditions, they can either be employed as ammonium complex halide salts [3], or in the molecular state with or without an added quaternary ammonium catalyst [4]. Stoichiometric amounts of tetra-n-butylammonium tribromide under pH controlled conditions oxidize primary alcohols and low-molecular-weight alkyl ethers to esters, a,cyclic ethers produce lactones [3], and secondary alcohols yield ketones. Benzoins are oxidized to the corresponding benzils (80-90%) by the tribromide salts in acetonitrile in the presence of benzoyl peroxide [5]. 

Benzyl-alkyl, dialkyl, cyclic and acyclic ethers were converted to esters or lactones by RuO or [RuO ] (RuClj/aq. Na(C10) or Ca(C10)j/CH2Cl2). It was not stated whether RuO or [RuO ] was the effective oxidant, but oxidation of jb-methoxy-benzyhnethyl ether apparently involved a one-electron transfer process, which might be more likely to occur with [RuO ] [426],... 

One of the most remarkable reactions performed by ruthenium-oxo complexes is the selective oxidation of aliphatic and cyclic ethers to the corresponding esters and lactones, respectively, with high yields under mild conditions.288,334 For example, tetrahydrofuran is oxidized by Ru04 to y-butyrolactone with nearly quantitative yields.334 A catalytic reaction can be carried out in the presence of excess hypochlorite or periodate.332,335... 

Methylenation.1 When heated in THF at 60-65°, this reagent effects methy-lenation of ketones, even readily enolizable ones, in 60-90% yield and of aldehydes (45-60% yield). It also converts esters and lactones into enol ethers, but this reaction is generally slower. It is thus an attractive alternative to the Tebbe and Grubbs reagent. 

More recently, worlc has been reported showing that silyl enol ethers of ketones, esters and lactones can be efficiently converted to a-sulfonyloxy carbonyl compounds on treatment with either [hydroxy(to-syloxy)iodo]benzene or [hydroxy(mesyloxy)iodo]benzene (equation 23). This method is similar to that used by the same workers to introduce the trifluoromethylsulfonyloxy group a to ketone carbonyl groups via their silyl enol ethers.While the major interest in these developments is the further func-tion zation of the a-position of carbonyl compounds the method clearly offers a route to a. -unsatu-rated species. 

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