Enol esters with alcohols

Iminophosphoranes (117), (118) and their polymer-supported analogues (119), (120) (Scheme 24) have been found to catalyse the acylation of primary alcohols with enol esters with high yields and selectivities. Moreover, these ylide based catalysts appear more tolerant of sensitive functional groups than alternative Lewis base reagents. ... 

The a-alkylation of esters is an important process in organic chemistry and the transition-metal-catalyzed a-alkylation of esters with alcohols using a transfer hydrogenation method represents an attractive alternative to conventional processes involving the reaction of metal-based enols with alkyUialides [169-171]. 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The enolic esters, on saponification, regenerate the aldehydes. With sodium and alcohol, the saturated alcohol corresponding to the aldehyde is obtained. 

For acyclic systems, the anti diastereoselectivity of the (i )-enolates is lower than the syn diastereoselectivity of comparable (Z)-enolates. For example, carboxylic acid esters, which form predominantly ( )-enolates, react with aldehydes with high anti selectivity only in those cases where bulky aromatic substituents are in the alcoholic part of the ester22 25. 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

Therefore, transesterification reactions frequently fail when R is tertiary, since this type of substrate most often reacts by alkyl-oxygen cleavage. In such cases, the reaction is of the Williamson type with OCOR as the leaving group (see 10-14). With enol esters, the free alcohol is the enol of a ketone, so such esters easily... 

It is possible to treat ketones with allyl alcohol and an acid catalyst to give y,5-unsaturated ketones directly, presumably by initial formation of the vinylic ethers, and then Claisen rearrangement.In an analogous procedure, the enolates (126) of allylic esters [formed by treatment of the esters with lithium isopropylcyclohex-... 

Boron enolates can be obtained from esters40,41 and amides42 by methods that are similar to those used for ketones. Various combinations of borylating reagents and amines have been used and the E.Z ratios are dependent on the reagents and conditions. In most cases esters give Z-enolates, which lead to syn adducts, but there are exceptions. Use of branched-chain alcohols increases the amount of anti enolate, and with t-butyl esters the product ratio is higher than 97 3. 

Keto acids can be dehydrated to enol lactones (Section III,A,1). They may also undergo esterification with alcohols e.g., /V-methylhydrasteine (104) in methanol at room temperature gave the expected keto ester 126 (R + R = CH2, R1 = CH3) (5,87). Sodium borohydride reduction of keto acid 104 supplies the saturated y-lactone 132 identical with that obtained from enol lactone 98 (5). 

Oxidative cleavage of the terminal double bond of 49 by ozonolysis to the aldehyde followed by permanganate oxidation to the acid and esterification with diazomethane produced the methyl ester 50. Dieckmann cyclisation of 50, following the procedure developed in Holton s laboratory (LDA, THF, -78 °C, 0.5 h, then HOAc, THF), gave the enol ester 5J in 93% yield (90% conversion). Decarbomethoxylation of 5J. was carried out by temporarily protection of the secondary alcohol (p-TsOH, 2-methoxypropene, 100%), and heating the resulting compound 52 with PhSK in DMF, at 86 °C (3 h) to provide 53a or, after an acidic workup, the hydroxy ketone 53b. 92% yield. 

Electrolytic reduction, apparatus, 52, 23 Enol acetates, acylation of, 52,1 Enol esters, preparation, 52, 39 Epichlorohydrin, with boron trifluoride diethyl therate and dimethyl ether to give trimethyloxonium tetra-fluoroborate, 51,142 ESTERIFICATION OF HINDERED ALCOHOLS f-BUTYL p-TOLUATE,... 

With enol esters, the free alcohol is the enol of a ketone, so such esters easily undergo the reaction... 

Alcohols can also be prepared from support-bound carbon nucleophiles and carbonyl compounds (Table 7.4). Few examples have been reported of the a-alkylation of resin-bound esters with aldehydes or ketones. This reaction is complicated by the thermal instability of some ester enolates, which can undergo elimination of alkoxide to yield ketenes. Traces of water or alcohols can, furthermore, lead to saponification or transesterification and release of the substrate into solution. Less prone to base-induced cleavage are support-bound imides (Entry 2, Table 7.4 see also Entry 3, Table 13.8 [42]). Alternatively, support-bound thiol esters can be converted into stable silyl ketene acetals, which react with aldehydes under Lewis-acid catalysis (Entries 3 and 4, Table 7.4). 

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