Radical Couplings as Key Steps for the Preparation of Derivatives of Nonactic Acid

Abstract

Summary. Free radical couplings from furan, as cheap starting material, were studied in view of developing a rapid strategy en route to the synthesis of derivatives of nonactin. The chain containing the alcohol function was introduced in one or two steps in 86% yield. For the introduction of the second chain with the ester function two different coupling methods were tested. Starting from the advanced intermediates obtained nonactin derivatives can be prepared by catalytic hydrogenation of the furan ring.

Macrocyclisation of 2-(5-(2-hydroxyethyl)furan-2-yl)acetic acid model compounds of nonactic acid

“…Under these modified conditions, the overall yield of macrocycles 12a-d decreased drastically. The use of the potassium cation has been reported to increase the yield of calix [9][10][11] furan formation [16], while chelation can be used for the assembly of furan rings into a macrocycle. In our case, the rigid furan rings reduce the flexibility needed for the assembly into macrocycles.…”

“…As part of our ongoing studies on macrocycle 1, we have developed a method for synthesising 2,5-disubstituted furans and tetrahydrofurans as nonactic acid precursors and analogues [9][10][11]. The key steps used to introduce the alkyl chains to the furan ring are radical couplings.…”

Malonylation/Decarbalkoxylation of Furan Derivatives as Key Steps for the Preparation of Nonactic Acid Derivatives. Part II [1]

“…19: Data were the same than under Baciocchi conditions. See data reported in the previous paper [4].…”

“…The life time of these electrodes is limited due to the loss of nonactin through bleeding. In the course of our studies for the preparation of hydrophobic nonactin derivatives [3], we described a rapid synthesis of derivatives of nonactic acid from furan applying different radical couplings for the introduction of the first aliphatic side chain [4]. In Ref.…”

Radical alkylation in the synthesis of phenacylfurans

“…In particular, there is a report in the literature of the radical alkylation of furan and 2-methylfuran by ethyl iodoacetate in the presence of the Fenton's reagent (H 2 O 2 / FeSO 4 in DMSO) [7,8]. It should be noted that the most popular reagents for radical alkylation are both iodides and xanthates [9].…”