Enol ethers rearrangements

Snider has shown that thermolysis of 2,6-dimethyl-2,7-octadienal at 350°C yielded three compounds, 365-367, having the iridoid skeleton. The lactone 368 was made by cyclization of the corresponding hydroxy acid ( 8-hydroxy-citronellic acid ), and its tert-butyldimethylsilyl enol ether rearranged in an Ireland-type Claisen rearrangement, yielding the iridoid acid 369 after removal of the silyl group with HF in acetonitrile. The latter was converted (by hydrobora-tion-oxidation) into both isomers of dihydronepetalactone (370) (erroneously considered to be unsynthesized by the authors, who clearly did not read Vol. 4, p. 497). Iridomyrmecin (371) is also accessible from 369 (Scheme 30). 

A number of steric effects on the rate of rearrangement have been observed and can be accommodated by the chairlike transition state model. The f -silyl enol ethers rearrange somewhat more slowly than the corresponding Z-isomers. This is interpreted as resulting from the pseudoaxial placement of the methyl group in the transition state for rearrangement of the -isomer. 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

This effect is the basis of the synthetic importance of ester enolate Claisen rearrangements in which enolates or silyl enol ethers of allylic esters are rearranged into 4-pentenoate esters. 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

Reaction of 1-ethoxycyclohexene (34) with dichlorocarbene gives 1-ethoxy-7,7-dichloronorcarane (35) in 87 % yield. Rearrangement of dichlorocyclo-propane (35) in hot quinoline results in loss of both chlorine atoms to give l-ethoxycyclohepta-l,3,5-triene (37) in 37% yield. Hydrolysis of enol ether (37) with a very small quantity of hydrochloric acid in methanol produces cyclohepta-3,5-dienone (38) in 91 % yield. ... 

Photochemical rearrangements of enol esters, enol lactones, and enol ethers... 

Claisen rearrangement of the allyl enol ether of tnfluoroacetylacetone gives a C-allylated derivative [123] (equation 106)... 

Geometrically defined a/ -epoxysilanes have been shown (6) to undergo a highly stereoselective rearrangement to silyl enol ethers (see also Chapter 15). This rearrangement is catalysed by boron trifluoride etherate, and seems to involved-opening of the epoxysilane, as shown ... 

Direct treatment of TIPS enol ethers of a variety of cyclic and acyclic ketones with the strong-base combination of n-BuLi/KO-t-Bu leads to /3-ketosilanes (2) after aqueous work-up. In contrast with the earlier method, this rearrangement appears to proceed through allylic, rather than vinylic, metallation, since enol ethers lacking an allylic a-proton are unreactive. 

Category 3. Intramolecular Rearrangement. Two examples are the rearrangement of the trimesityl compound (1) to the enol ether (2), " and irradiation of o-nitrobenzaldehydes (3) to give o-nitrosobenzoic acids (4)." ... 

Fig. 6.14. Possible transition structures for [3,3]-sigmatropic rearrangement of 2-cyclohexenyl ester enol ethers. Adapted from J. Org. Chem., 68, 572 (2003), by permission of the American Chemical Society.

When this reaction sequence is applied to enol esters or enol ethers, the result is a-oxygenation of the starting carbonyl compound. Enol acetates form epoxides that rearrange to a-acetoxyketones. 

The synthesis in Scheme 13.44 is also based on a carbohydrate-derived starting material. It controlled the stereochemistry at C(2) by means of the stereoselectivity of the Ireland-Claisen rearrangement in Step A (see Section 6.4.2.3). The ester enolate was formed under conditions in which the T -enolate is expected to predominate. Heating the resulting silyl enol ether gave a 9 1 preference for the expected stereoisomer. The... 

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