Stereoselective Favorskii rearrangement of carvone chlorohydrin; expedient synthesis of (+)-dihydronepetalactone and (+)-iridomyrmecin

Abstract

+)-Di hydronepetalactone and (+)-iridomyrmecin were synthesized from the stereoselective Favorskii rearrangement product of (+)-cawone chlorohydrin.Functionalized cyclopentanecarboxylates are obtained from the Favorskii rearrangement of cyclohexanone derivatives, e.g., Favorskii rearrangement of the monoepoxide 1 of (-)-carvone afforded a highly functionalized cyclopentanecarboxylic acid 2 albeit in low yield' (Scheme 1).The stereochemical array in 2 requires cyclopropanone derivative 3 as an intermediate (presumably formed by the SN2 type displacement of the epoxide moiety) in which the selective cleavage of the bond between C-1 and C-2 is coupled with the stereoselective protonation at C-2 resulting in retention of the stereochemistry. We prepared the chlorohydrin derivative of (-)-carvone to examine Favorskii rearrangement. The Favorskii rearrangement of the chlorohydrin 4 is very efficient and provides a valuable cyclopentanecarboxylate derivative 5 , and its enantiomer 8 is converted into cat-a ttracting iridolactones ,2 ( + )-di hydronepe talactone 113 and (+)-iridomyrmecin 14.4

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

“…Subsequently, the aldehyde 15 was reduced to the allylic alcohol 19 with LiAlH 4 and converted into the acetate 20 [28]. Hydroboration of 20 using disiamylborane proceeded with high stereoselectivity affording 16 as a single stereoisomer [17,28]. Similar results of highly stereoselective hydroborations of structurally related chiral cyclopentene derivatives have been reported [20–21].…”

Synthetic Route Development for the Laboratory Preparation of Eupalinilide E

“…The organic layer was separated, washed with 0.1 N HCl (2 × 10 mL) and 3.0 N LiCl (10 mL), dried over Na 2 SO 4 , and concentrated in vacuo to give crude aldehyde 27 as a clear oil, which was used immediately in the next reaction without purification: R f = 0.57 (silica gel, 3/1 hexanes/EtOAc); 1 H NMR (400 MHz, CDCl 3 ) δ 9.30 (d, J = 3.1 Hz, 1H), 7.25 (d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 5.75 (m, 1H), 5.17 (s, 1H), 5.09 (q, J = 2.3 Hz, 1H), 4.98 (q, J = 2. 4 (3aS,4S,6aR,7R,9aR,9bS)-7-((4-Methoxybenzyl)oxy)-9-methyl-3,6-dimethylene-2,3,3a,4,5,6,6a,7,9a,9b-decahydroazuleno-[4,5-b]furan-4-ol (28). To a stirred solution of crude aldehyde 27 (180 mg, 0.49 mmol, 1.0 equiv) in CH 2 Cl 2 (4.8 mL, 0.1 M) at −78 °C was added a 1.0 M solution of diethylaluminum chloride in hexanes (244 μL, 0.24 mmol, 0.5 equiv) in a single portion.…”

Carvone as a Versatile Chiral Building Block for Total Syntheses of Heterocyclic Sesquiterpenoids

“…(1) into cyclopentanecarboxylate 173, which has, since then, been utilized as a versatile precursor for syntheses of the cis-fused hydroazulenic ring system in a variety of guaiane natural products (Scheme 16) [27]. Stereoselective epoxidation of R-carvone (1) to epoxide151, followed by diaxial ring opening of the epoxide by Subsequently, Lee et al completed the total synthesis of (+)cladantholide (180) employing tandem 5-exo-and 7-endo-radical cyclizations starting from the cyclopentanecarboxylate 172 (Scheme 17) [28].…”

“…(1) into cyclopentanecarboxylate 173, which has, since then, been utilized as a versatile precursor for syntheses of the cis-fused hydroazulenic ring system in a variety of guaiane natural products (Scheme 16) [27]. Stereoselective epoxidation of R-carvone (1) to epoxide151, followed by diaxial ring opening of the epoxide by Syntheses of heterocyclic sesquiterpenoids starting from carvone Natural Product Communications Vol.…”

“…Total synthesis of (-)-ligurarenolide (166) and (-)-PF1092C (170) by Jenniskens and de Groot[26].Scheme 16: Transformation of R-(-)-carvone(1) into cyclopentane derivative 173 as a precursor for guaianolide synthesis by Lee and Yoon[27].…”