Sodium enolates Claisen rearrangement

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

Historically, as early as 1937, the first enolate Claisen rearrangement, though it was not formally recognized as such, was documented. Tseou and Wang [12] reported the formation of 4-pentenoic acid in low yields on heating neat allyl acetate with sodium metal for 3 h to ca. 100°C while attempting the acetoacetic ester synthesis (Scheme 5.1.1). 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

Condensation of the sodium enolate of acetylacetone 194 with carbethoxy-cyclopropyltriphenyl tetrafluoborate 195 led in high yield to acetylcyclopen-tenyl ester 196 and thence to ketal aldehyde 197. The latter with m-methoxy-phenethyl magnesium chloride 198 yielded allylic alcohol 199, which on Claisen rearrangement with dimethylacetamide dimethylacetal afforded amide 200. Conversion to amine, amine oxide, and Cope elimination then led to the desired... 

The first total synthesis of the intricate Stemona alkaloid (+ /—)-isostemofoline (224) was reported by Kende and coworkers 81) starting from 1,2-hexanediol (225) which was straightforwardly converted to 227 (Scheme 22) 82). Reductive cycUzation with sodium hydrosulfite in refluxing aqueous ethanol, and protection of the unstable pyrrole as tert-butyl carbamate, afforded 228 in five steps with 12% overall )deld. The key bicyclic ketone 231 was assembled by [4 + 3] cycloaddition of pyrrole 228 and diazoester 229 promoted by rhodium octanoate dimer, followed by enol silane deprotection, exo-specific hydrogenation, and nucleophilic decarboxylation (47% overall yield). Sodium methoxide-catalyzed aldol condensation of ketone 231 and furfural provided the Q-j/i-unsaturated ketone 232 whose olefin configuration was established by nOe studies. Allylation of 232 provided a 2.4 1 mixture of ketone 234 and the corresponding allylic enol ether 233, which could be converted to the former via a stereoselective Claisen rearrangement. 

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