Oxazoline lactone formation

In intramolecular cyclopropanation, Doyle s catalysts (159) show outstanding capabilities for enantiocontrol in the cyclization of allyl and homoallyl diazoesters to bicyclic y-and -lactones, respectively (equations 137 and 138) The data also reveal that intramolecular cyclopropanation of Z-alkenes is generally more enantioselective than that of -alkenes in bicyclic y-lactone formation . Both Rh(II)-MEPY enantiomers are available and, through their use, enantiomeric products are accessible. In a few selected cases, the Pfaltz catalyst 156 also results in high-level enantioselectivity in intramolecular cyclopropanation (equation 139) ". On the other hand, the Aratani catalyst is less effective than the Doyle catalyst (159) or Pfaltz catalyst (156) in asymmetric intramolecular cyclo-propanations In addition, the bis-oxazoline-derived copper catalyst 157b shows lower enantioselectivity in the intramolecular cyclopropanation of allyl diazomalonate (equation 140). ... 

Entry 10 was used in conjunction with dihydroxylation in the enantiospecific synthesis of polyols. Entry 11 illustrates the use of SnCl2 with a protected polypropionate. Entries 12 and 13 result in the formation of lactones, after MgBr2-catalyzed additions to heterocyclic aldehyde having ester substituents. The stereochemistry of both of these reactions is consistent with approach to a chelate involving the aldehyde oxygen and oxazoline oxygen. 

In 1982, Evans reported that the alkylation of oxazolidinone imides appeared to be superior to either oxazolines or prolinol amides from a practical standpoint, since they are significantly easier to cleave [83]. As shown in Scheme 3.17, enolate formation is at least 99% stereoselective for the Z(0)-enolate, which is chelated to the oxazolidinone carbonyl oxygen as shown. From this intermediate, approach of the electrophile is favored from the Si face to give the monoalkylated acyl oxazolidinone as shown. Table 3.6 lists several examples of this process. As can be seen from the last entry in the table, alkylation with unactivated alkyl halides is less efficient, and this low nucleophilicity is the primary weakness of this method. Following alkylation, the chiral auxiliary may be removed by lithium hydroxide or hydroperoxide hydrolysis [84], lithium benzyloxide transesterification, or LAH reduction [85]. Evans has used this methology in several total syntheses. One of the earliest was the Prelog-Djerassi lactone [86] and one of the more recent is ionomycin [87] (Figure 3.8). 

As previously aluded to, Bolm has used Cu with a chiral oxazoline S,S-cat to promote the asymmetric formation of lactones from racemic ketones. This catalyst worked well only on 2-phenylcyclohexanones.32... 

Besides the more often-used acyl donors mentioned above, others which would also ensure an irreversible type of reaction have been investigated [170]. Bearing in mind that most of the problems of irreversible enzymatic acyl transfer arise from the formation of unavoidable byproducts, emphasis has been put on finding acyl donors that possess cyclic structures, which would not liberate any byproducts at all. However, with candidates such as lactones, lactams, cyclic anhydrides (e.g., succinic acid anhydride [171]), enol lactones (e.g., diketene [172, 173]), and oxazolin-5-one derivatives [174], the drawbacks often outweighed their merits. 

Similarly, Ohveira et al. have reported the synthesis of all four possible dia-stereomers of a component of the pheromone blend of the carpenter bee Xylocopa hirutissima via alkylation of 4,4-dimethyl-2-oxazoline derivatives [61] (Scheme 23). In this case, the carboxylic acid, allowing the formation of the 5-lactone, is masked as an oxazoline. The reaction of the anion of 2-ethyl-4,4-dimethyl-2-oxazoline 120 with iodide 121 gave compound 122 in 92 % yield, which was hydrolyzed and cyclized in one-pot under acidic conditions to provide a mixture of stereoisomers 123 and 124. 

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