Acetoxylactone

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

AcOH, followed by hydrolysis, gives the (/ )- , 3-dienecarboxylic acid 152. Then the acetoxylactone 153 can be prepared by the Pd-catalysed intramolecular trans-1,4-functionalization of the 1,3-cyclohexadiene 152. On the other hand, the acetate 155 is obtained by the Pd-catalysed chemoselective displacement of the allylic carbonate moiety in 154 with malonate under neutral conditions. The (5)-1,3-dienecarboxy 1ic acid 156 is obtained by Pd-catalysed 1,4-elimination of 155. The Pd-catalysed 1,4-functionalization of the 1,3-cyclohexadiene 156 and acetylation, afford 157, which is an enantiomer of 153 [101]. 

The palladium-catalyzed lactonization reaction has also been performed with hcxadicnyl acetic acids leading, under different reaction conditions, to either trans- or cis-acetoxylactonization products46. 

In a similar manner, the diacetates from cyclic dienes were enzymatically hydrolyzed and transformed to the enantiomers of diene acids 50 [71]. The diene acids from the seven-membered ring were subsequently used in intramolecular cis- and trans-1,4-acetoxylactonizations (cf. Scheme 8-14), leading to four different isomers of enantiomerically pure lactones. 

In this reaction a useful stereocontrol was obtained by the use of LiCl as a catalytic additive. Without added LiCl a l,4-fr(ins acetoxylactonization took place, while in the presence of a catalytic amount of LiCl a 1,4-ds acetoxylactonization occurred. This is in analogy with the diacetoxylation of conjugated dienes discussed above where chloride ions block the coordination of acetate to palladium. At an increased chloride ion concentration (as added LiCl) a highly regio- and stereoselective 1,4-ds chlorolactonization took place. The presence of the 7r-allylpalladium intermediate 40 was demonstrated by its isolation and stereochemical assignment. The tram stereochemistry between palladium and oxygen in the 7r-allylpalladium complex 40 was established by the use of reporter ligands and NOE measurements . 

In the case of certain unsaturated carboxylic acids treatment with Pb(OAc)4 leads to the formation of an acetoxylactone, for example (12).70,1... 

Acetoxylactonization. Unsaturated carboxylic acids undergo oxidative cycli-zation in the pre.sence of triflic acid in acetic acid. 

One of the most practical approaches among those described in Fig. (4) involves optical resolution of hydroxylactone rac-13, which is readily derived from acetoxylactone rac-1, an intermediate of Goldberg-Sternbach approach, by the treatment with hydrochloric acid (HC1) (Fig. (5)) [55]. The optical resolution of rac-13 with natural... 

Intramolecular 1,4-Diacyloxylation An intramolecular variant of the palladiumutilizing dienes with a carboxyl group in the side chain (Scheme 11.16) [75, 76]. Also in this case the stereochemistry of the 1,4-addition can be controlled by variation of the ligand environment. Thus, in the absence of chloride a trans acetoxylactonization takes place, whereas in the presence of a catalytic amount of chloride a cis acetoxylactonization occurs. The catalytic intermediate was isolated and stereochemically assigned as its bipyridyl complex 49 [76]. In the stereochemical assignment, bipyridyl was utihzed... 

Reactions with benzoquinone as the reoxidant are shown in eqs. (20.58) and (20.59). Acetoxylactonization products are prepared stereoselectively according to the reaction conditions [192]. 

Regio- and enantiodifferentiation, however, can be found for the selective hydrolysis of 2-0-acyllactones. Thus, 2-O-acylpantoyllactones 316 (Fig. 78) gave (5)-204 and (/ )-316 [317,487]. Similarly, the deacetylation of the carbohydrate-derived a-acetoxylactone 318 afforded 319, whereas 320 was not affected by lyophilized BY [488,489]. 

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