m-Chloroperbenzoic acid → Epothilone A

HRID 2306281Notes

Reaction equation

C1C=C(Cl)C=[C:3]([C:8]([O:10][OH:11])=O)C=1.[CH3:12][C:13]1[S:17][CH:16]=[C:15](/[CH:18]=[C:19](/[C@H:21]2[O:39][C:37](=[O:38])[CH2:36][C@H:35]([OH:40])[C:34]([CH3:42])([CH3:41])[C:32](=[O:33])[C@H:31]([CH3:43])[C@@H:30]([OH:44])[C@@H:29]([CH3:45])[CH2:28][CH2:27][CH2:26][C@H:24]3[O:25][C@H:23]3[CH2:22]2)\[CH3:20])[N:14]=1>>[CH3:12][C:8]1([CH3:3])[O:10][O:11]1.[CH3:12][C:13]1[S:17][CH:16]=[C:15](/[CH:18]=[C:19](/[C@H:21]2[O:39][C:37](=[O:38])[CH2:36][C@H:35]([OH:40])[C:34]([CH3:42])([CH3:41])[C:32](=[O:33])[C@H:31]([CH3:43])[C@@H:30]([OH:44])[C@@H:29]([CH3:45])[CH2:28][CH2:27][CH2:26][C@H:24]3[O:25][C@H:23]3[CH2:22]2)\[CH3:20])[N:14]=1

Participants

Reactant 2

HCID 70297m-Chloroperbenzoic acid

HCID 448799Epothilone A

Product 2

HCID 115197Dimethyldioxirane

HCID 448799Epothilone AYield 50%

Procedure

The cis-olefin 49 was converted to epothilone A (1) by the action of mCPBA (0.8-1.2 equivalents) in a reaction that, in addition to 1 (35% yield), produced the isomeric epoxides 51 (13% yield), 52 (or 53) (9% yield, stereochemistry unassigned) and 53 (or 52) (7% yield, stereochemistry unassigned), as well as bis(epoxides) 54 (or 55) and 55 (or 54) (10% total yield, stereochemistry unassigned). Reaction of olefin 49 with excess mCPBA (1.3-2.0 equivalents) gave a different product distribution: 1 (15%), 51 (10%), 52 (or 53) (10%), 53 (or 52) (8%), 54 (or 55) (8%), 55 (or 54) (7%), 56 (5%), and 57 (5%). The action of dimethyldioxirane (Murray et al. J. Org. Chem. 1985, 50, 2847-2853) (Methylene chloride, 0° C.) on 49 gave mainly 1 (50%) and 51 (15%), together with small amounts of 53 (or 54) and 54 (or 53) (10% total yield).

Workup

customgave a different product distribution

Sources & evidence

ORD record: ord-9f99d539fa9b4cdb967d68b25f671f68
Source dataset: uspto-grants-2002_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06441186B1

Reaction notes

Loading…