Lactones, from vinyl ethers

The methylenation of esters or lactones with 30, followed by further transformation, constitutes a useful synthetic protocol (Scheme 4.27). A carbonyl methyl-enation-Claisen rearrangement strategy using 30 is employed for the construction of medium- and large-ring ketones from lactones [78]. A phenol derivative has also been synthesized by treatment of a protected quinol ester with 30, which involves thermal rearrangement of the intermediate vinyl ether [79]. 

Dehydrobromination of bromotrifluoropropene affords the more expensive trifluoropropyne [237], which was metallated in situ and trapped with an aldehyde in the TIT group s [238]synthesis of 2,6-dideoxy-6,6,6-trifluorosugars (Eq. 77). Allylic alcohols derived from adducts of this type have been transformed into trifluoromethyl lactones via [3,3] -Claisen rearrangements and subsequent iodolactonisation [239]. Relatively weak bases such as hydroxide anion can be used to perform the dehydrobromination and when the alkyne is generated in the presence of nucleophilic species, addition usually follows. Trifluoromethyl enol ethers were prepared (stereoselectively) in this way (Eq. 78) the key intermediate is presumably a transient vinyl carbanion which protonates before defluorination can occur [240]. Palladium(II)-catalysed alkenylation or aryla-tion then proceeds [241]. 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

The cyclohexanone (S3), an intermediate for the synthesis of thromboxane antagonists, has been prepared by a combination of phosphine oxide- and phosphonium ylide-based olefinations.30 Reaction of the lactone (50) with methoxymethyldiphenylphosphine oxide anion gave a poorly characterized adduct (presumably (51)) which on reduction with sodium borohydride, followed by treatment with sodium hydride gave the vinyl ether (52) in 80% overall yield from (SO) (Scheme 8). Further modification gave the required cyclohexanone (53). 

A large number of copolymers of cyclic ethers, cyclic sulphides and cyclic formals have been prepared. Many cyclic compounds that will not homopolymerize do copolymerize readily [7, 146,147]. Some cyclic compounds will copolymerize with lactones, cyclic anhydrides, or vinyl monomers. Very many commercially important materials have resulted from these copolymerizations. 

The Chiron (-)-(lOa) was obtained with very high diastereoselectivity from a-pyrone sulfone and optically active vinyl ether (Scheme 69). This lactone was later used in the asymmetric synthesis of (-)-methyltriacetyl-4-epishikimate (10b). 3-Sulfonylnitroalkenes were also shown to be reactive alkyne equivalents in Diels-Alder reactions. ... 

When both alkenes (allyl and vinyl ether) are inside a ring the stereochemical problems are much simplified. The reaction inevitably leads to ring contraction and a simple example is Funk s synthesis37 of chrysanthemic acid 197 from the seven-membered lactone 195. The silyl enol ether 196 rearranges to c/ s-chrysanthemic acid in very high yield. A chair transition state is impossible in this restricted molecule. 

An early synthesis of lactacystin, not via the P-lactone, used glucose as starting material.20 Disconnection to 115 (the vinyl group can be converted into COzH and the benzyl ether into CHO) gives a structure that can be redrawn as 116 and then, with incorporation of an extra C atom (to be removed in the synthesis by diol oxidation) derived from 117. 

A very carefully thought out test of the reahty of electrostatic stabilisation of a developing oxocarbonium ion was applied by Loudon and Ryono [95] using compounds XXXIV and XXXV. (The oxocarbonium ion is generated by rate-determining proton transfer to the vinyl ether function, rather than by departure of a leaving group.) Neither carboxylate can participate nucleophihcally any lactone from XXXIV would be unconscionably strained. Furthermore, water molecules in XXXIV cannot be accommodated between the carboxylate and the oxocarbonium ion centre the endo face of the system is hydrophobic. 

With a cyclic substrate, for example in which three or more atoms of the allyl vinyl ether are constrained in aring, then the boat-shaped transition state maybe favoured. Formation of the silyl ketene acetal from the lactone 295 and rearrangement on warming gave the carboxylic acid 296 (3.190). The reaction occurs via a boatshaped transition state and was used in a synthesis of the sesquiterpene widdrol. 

Palladium-catalyzed cyclizations of bromodialkenyl ethers, in which the key step is vinylic substitution of bromine, result in low to moderate yields of tetrahydrooxepines and methyleneoxepanes <83JOC3894>. y,5-Unsaturated seven-membered lactones are prepared in 50-60% yields from 2-phenylthio-3-butenyldiazomalonates <90CL613> on treatment of the latter with rhodium acetate the reaction involves a [2,3]-sigmatropic rearrangement of the generated cyclic allylsulfonium ylides. 

---