Manganese(III)-based oxidative free-radical cyclizations. Oxidative cyclization and aromatization of 3-oxo-6-heptenoate esters

Abstract

Treatment of 3-oxo-6-heptenoate esters 1, 2, 4-15 with 4 equiv of Mn(0Ac)3-2H20 and 1 equiv of Cu(0Ac)2-H20 gave salicylate esters 16-29 in yields of 17-78%. Similar treatment with 4 equiv of Mn(0Ac)3-2H20 and excess LiCl gave mixtures of salicylate esters and chlorides such as 45 and 46, which could be converted to the salicylate ester by heating at reflux in acetic acid containing excess LiCl in overall yields of 40-90%. Treatment of a-chloro /3-keto ester 3 with 2 equiv of Mn(0Ac)3-2H20 and 1 equiv of Cu(0Ac)2-H20 gave a mixture of salicylate 17 and methylenecyclohexane 41. Treatment of 5-hydroxy /3-keto esters 51a and 51b with 2 equiv of Mn(0Ac)3-2H20 gave epoxides 53a and 53b in 50% and 30% yield, respectively.

Intramolecular [2+2] Photocycloaddition Reactions as an Entry to the 2‐Oxatricyclo[4.2.1.04, 9]nonan‐3‐one Skeleton of Lactiflorin

“…Selective syn ‐reduction of the known methyl 5‐hydroxy‐3‐oxo‐6‐heptenoate ( rac ‐ 17 )20 to product rac ‐ 18a could be easily realized with Et 2 B(OMe)/NaBH 4 ,21 and reduction with NMe 4 BH(OAc) 3 led anti ‐selectively to 1,3‐diol rac ‐ 18b (Scheme…”

“…Along these lines, lactones rac-21 and rac-23, which show an opposite 1,3-dioltype relationship to the stereogenic center at the lactone, were synthesized. Selective syn-reduction of the known methyl 5-hydroxy-3oxo-6-heptenoate (rac-17) [20] to product rac-18 a could be easily realized with Et 2 BA C H T U N G T R E N N U N G (OMe)/NaBH 4 , [21] and reduction with NMe 4 BHA C H T U N G T R E N N U N G (OAc) 3 led anti-selectively to 1,3-diol rac-18 b (Scheme 5). [22] The syntheses of syn-and anti-photocycloaddition precursors followed an identical synthetic scheme starting from the corresponding diols (Scheme 6).…”

Mechanisms of Mn(OAc)3-based oxidative free-radical additions and cyclizations

“…Oxidative cyclization of δ-hydroxy β-keto ester 73 affords epoxide 75 as the major product in 50–60% yield 26. β-Hydroxy radical 74 is oxidized to the epoxide by either Mn III or Cu II in a process that is analogous to the oxidation of radical 4 to lactone 8 .…”

“…The combination of Mn(OAc) 3 and LiCl has seen very limited synthetic applications because the chlorides that are formed are of little utility. However, oxidation of 80 with Mn(OAc) 3 and excess LiCl forms 81 , which reacts further to give 82 as the major product 4,26…”

“…For instance, oxidative cyclization of 96 provides 78% of methyl salicylate ( 99 ) (see Scheme 13). 26 Oxidative cyclization gives radical 97 ; oxidation of 97 by Cu II gives 98 , probably as a mixture of double-bond positional isomers. The unsaturated cyclic β-keto ester 98 is more acidic than 96 and is rapidly oxidized further by 2 equiv of Mn III to give a cyclohexadienone that tautomerizes to phenol 99 .…”