Triethylamine → HCID 24770098, compound

In accordance with scheme 4, the substrate 1,6 diol (21) is protected with benzyl group by using benzyl bromide in dry THF to obtain mono-benzyl ether (22), subsequently undergoes to TEMPO catalyzed oxidation in presence of iodobenzene diacetate in organic solvent such as DCM, DMF, affords aldehyde (23). Further the obtained aldehyde on proline-catalyzed direct asymmetric α-aminoxylation using nitrosobenzene in acetonitrile as an oxygen source, followed by treatment with NaBH4 in methanol affords intermediate compound; further obtained compound is treated with copper (II) acetate in methanol for 24 hrs gives the corresponding chiral diol (24). The selective tosylation of the diol (24) using tosyl chloride, triethylamine, and catalytic amount of dibutyltin oxide (Bu2SnO) in DCM furnishes the mono tosylated compound, which is further treated with potassium carbonate in dry methanol at 0° C. for 20-40 mins gives the epoxide (25). Further the epoxide is treated with LAH in dry ether to afford chiral secondary alcohol (26), subsequently the hydroxyl group of (26) is protected by TBS by using TBS-Cl, imidazole in DCM to obtain compound (27), the benzyl group is further cleaved in presence of palladium catalyzed reduction in ethyl acetate gives TBS protected alcohol (28). The obtained alcohol on TEMPO catalyzed oxidation in presence of iodobenzene diacetate in organic solvent yields aldehyde (29). Further the α-aminoxylation of aldehyde (29), is carried out using nitrosobenzene as the electrophilic component followed by in situ Horner-Wadsworth-Emmons olefination with DBU as base that furnishes anilinoxy olefinic ester. The deprotection of anilinoxy group to hydroxyl group is achieved with Cu(OAc)2 in ethanol gives olefin ester (30), further protecting hydroxyl group of (30) in presence of MOMCl and DIPEA in DCM furnishes ester (31). The ester thus formed on reduction by using DIBAL-H in dry DCM at temperature range from −70° C. to −85° C. affords corresponding aldehyde (32), the obtained aldehyde on Wittig reaction in dry THF at temperature range from −70° C. to −85° C. forms ester (33). The TBS group is further cleaved in presence of TBAF in THF to afford (34). Subsequently, hydrolysis of the ester with LiOH in methanol and water yields the corresponding carboxylic acid (35). The acid is further subjected to Yamaguchi macrolactonization conditions i.e. acid (35) is treated with 2,4,6-trichlorobenzoyl chloride and triethylamine in THF, reflux with DMAP, in toluene to afford the MOM protected decanolide (36) further the deprotection of MOM group give rise to desired decanolides i.e. Stagonolide-E in high yield, 40% overall and purity, 98% enantiomeric purity.

1. customto afford the MOM

ORD record

ord-3db57930b8fa440584ef7452f5ecf67d

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353077B2