Lactone rearrangement fragmentation

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

Besides fragmentation or rearrangement, the carboxylic acid anions, formed by an enzymatic hydrolysis, can also act as nucleophiles. Kuhn and Tamm used the asymmetric hydrolysis of meso-epoxy diester 8-28 with PLE to synthesize y-lactone... 

Fig. 2 -31. Reactions of sugars in the presence of concentrated mineral acids, (a) Pentoses (R = H) yield furfural and hexoses (R = CH2OH) hydroxymethylfurfural. (b) On further heating hydroxymethylfurfural is fragmented under liberation of formic acid. The rest of the molecule is rearranged to levulinic acid, which is lactonized to form a- and /3-angelica lactones.

The structure of 19 was unambiguously confirmed by an X-ray diffraction study. A mechanistic rationale is depicted in Scheme 11. After Co2(CO)6-complexed alkyne A is obtained, a Sn2 attack of the Co2(CO)6 fragment opens the epoxide moiety to afford intermediate B, which subsequently incorporates CO to give C. The latter rearranges into cobalt-stabilized cyclic allene species D. The net result is a [5 + 1] cyclization that creates the lactone group. Coordination of the tethered olefin leads to oxidative cyclization to give E. Finally, insertion of CO followed by reductive elimination affords the desired product 19. 

A new approach to the synthesis of Prelog-Djerassi Lactonic acid (1) is reported. A key step in this synthesis involves an Ireland-Claisen rearrangement/silicon-mediated fragmentation sequence to provide the carbon framework in (1). 

In a second chelation-controlled addition, 286 is converted to 287 by addition of Grignard reagent to the acetyl carbonyl (80 1 diastereoselectivity) followed by lactonization. Di-oxanone-dihydropyran Claisen rearrangement (287- 288) establishes the desired carbon skeleton. It is ironic that the original (iS)-lactate stereocenter, which was responsible for all the stereochemistry, is ultimately destroyed in 289. An additional 11 steps is required to reach the target C-7 to C-13 fragment [103]. 

A Beckmann fragmentation of oximes using tosyl chloride in a basic ethanol-water system has also been observed. Formation of the cyclic product shown in eq 25 was consistent with a base-induced opening of an intermediate lactone followed by rearrangement and incipient extrusion of benzoic acid. 

The reactions of HTIB with alkenes (Scheme 3.73) can be rationalized by a polar addition-substitution mechanism similar to the one shown in Scheme 3.70. The first step in this mechanism involves electrophilic flnfi-addition of the reagent to the double bond and the second step is nucleophilic substitution of the iodonium fragment by tosylate anion with inversion of configuration. Such a polar mechanism also explains the skeletal rearrangements in the reactions of HTIB with polycyclic alkenes [227], the participation of external nucleophiles [228] and the intramolecular participation of a nucleophilic functional group with the formation of lactones and other cyclic products [229-231]. An analogous reactivity pattern is also typical of [hydroxy(methanesulfonyloxy)iodo]benzene [232] and other [hydroxy(organosulfonyloxy)iodo]arenes. 

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