Lactones, allylic stereospecific reaction

The synthon of the a-acrylate anion is available from a secondary a-keto carboxamide by the Shapiro reaction. The secondary a-ketoamide trisylhydrazones ate ptepar in a one-pot synthesis by reaction of the isocyanides with acid chloride, water and trisylhydrazine in sequence. In DME solvent, the hydra-zone (103) is smoothly metallated with BuLi to give Ae trianion (KH). Allylation of the trianion (104) gives the hydrazone (105). Alternatively, warming (104) up to room temperature yields the dianion (106) which can be intercepted with several electrophiles (Scheme 23). The adduct (107) is readily transformed into the rran -iodo lactone (108) stereospecifically (equation 56). This chemistry also has been applied to a new synthesis of -lactams (Scheme 24). ... 

Many examples of stereospecific allylation consistent with the above mechanism have been reported. As one example, the regioselective and highly diastereoselective allylation of the lactone 17 with the optically active allylic phosphate 16 proceeded with no appreciable racemization of the allylic part to give the lactones l8 and 19, and the reaction has been used for the synthesis of a polypropionate chain[26]. 

The reaction of 3-ketoacids with allyl carboxylates is also believed to proceed via a palladium enolate intermediate.126 Less than complete stereospecificity is also observed in these reactions (equation 163). Interestingly, the bicyclic lactone substrate employed to ascertain the stereointegrity of this reaction, in addition to being incapable of any syn-anti isomerization, cannot epimerize the starting material by car-boxylate attack at the metal. The observed stereochemical leakage could be due to epimerization of the intermediate allyl complex (equation 164) or reductive elimination of an allylpalladium enolate (retention) (equation 165). 

It was also discovered that these reactions can be conducted intramolecular-ly and that they remain stereospecific. For example, imino ene reaction of the N-sulfonyl imine derived from 246 produced two cis <5-lactones 248 and 250 as a 9 1 mixture (Scheme 44). The formation of the major (E)-product 248 can be rationalized by invoking the more favorable pericydic endo ene transition state 247. The minor (Z)-product 250 would arise from endo ene transition state 249, which suffers from A1,3 strain between the allylic methyl substituent and the cis vinyl hydrogen. Rather surprisingly, the Z -olefin isomer corresponding to 246 gave the same 9 1 mixture as did the E isomer. Based on the related loss of stereoselectivity with Z-2-butene (vide supra) it was again postulated that the... 

Allylic alcohol 846 has been employed in the synthesis of several natural products, as illustrated in Scheme 114 for the preparation of ( —)-elenolic acid (856), a secoiridoid monoterpene isolated from the olive Olea europea. The initial reaction is an orthoester Claisen rearrangement of 846 using triethyl orthoacetate, followed by lactonization with pyridinium / -toluenesulfonate. The resulting lactone is obtained as a 3 1 mixture of cw-850 and its trans isomer. After stereospecific alkylation of 850 with allyl bromide, the conversion of 851 to 852, which is essentially an expansion of the lactone by insertion of a methylene unit, requires five steps to accomplish. The remainder of the synthesis is uneventful, and furnishes pure 856 [234]. 

The Pd-catalyzed a-allylation of esters was first achieved by the reactions of aUylic carbonates with ketene silyl acetals that can be generated by treating esters with McsSiCl in the presence of a base. The yields of the desired products based on ketene silyl acetals were generally good except in the allylation of lactones (Scheme Selection of solvents is critical since the use of nitriles, such as MeCN and PhCN, leads only to the formation of a,/3-unsaturated esters rather than the a-ally-lated products. Both Reformatsky reagents and lithium enolates of esters have also been successfully a-allylated in the presence of Pd catalysts (Scheme 10). A highly regio- and stereospecific allylation of y-butyrolactone with ( )-2-hexenyl acetate is noteworthy. Since the lithium enolate of esters would react with allylic chlorides even in the absence of a Pd catalyst, however, it is not clear to what extent the reaction is catalyzed by a Pd complex. 

Deprotonation of cationic olefin complexes [Fe(CO)2(olefin)( -C6H5)]+ gives j -allyl complexes with a stereochemistry which is accounted for by preferred abstraction of an allylic proton trans to the Fe—olefin bond. The reverse reaction, protonation of the allyl complexes, is, however, non-stereospecific. Proton abstraction from the allyl alcohol derivative (3) by EtsN gives the lactone (4) in only one diastereoisomeric form, probably as a result of the alcohol in (3) having a preference for the conformation illustrated. Addition of MeO to similar olefinic cations (5) proceeds with high regioselectivity while amines add similarly to give complexes of... 

Dehydration of compounds (653 R = H or Ph) by toluene-p-sulphonic acid in benzene proceeds by homo-allylic rearrangement to give (654 R = H or Ph) some unrearranged olefin is obtained in the dehydration of (653 R = Ph). The cycliza-tion of ethyl (cyclo-oct-4-enylidene) acetate with BFajOEtj in hot benzene affords (655) and the corresponding acid (656). The bridgehead cation (657) is the presumed reaction intermediate. Aluminium chloride-catalysed cyclization of the lactone (658) resulted in the stereospecific formation of the carboxylic acid (660) the epimeric lactone (659) produced a mixture of a hexahydrofluorene carboxylic acid and the epimeric benzobicyclononene acid (661) mechanisms are discussed. 

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