High‐pressure [2 + 4]‐cycloaddition of dimethylmaleic anhydride to 3,4‐dimethoxyfuran; synthesis of dimethoxycantharidin preliminary communication

Abstract

As an active diene (more active than furan itself), 3,4-dimethoxyfuran (1) affords with many dienophiles the respective cycloadducts in a high yield [2]. It has recently been found that under thermal conditions 1 easily reacts with maleic anhydride and its monomethyl derivative, but not with dimethylmaleic anhydride (2) [3]. This is probably due to steric hindrance resulting from the location of two methyl groups on the double bond of the dienophile. Since all Diets-Alder reactions -in particular those with steric hindrance -are pressure-sensitive [4], we resolved to perform the title reaction under conditions of static high pressure. Scheme

Hyperbaric reactions in organic synthesis. Progress from 2006 to 2021

“…In the short introduction to the first part of the account, we cannot fail to mention once again the outstanding survey on the title topic 12 and the huge work done by the authors in the process of collection and generalization of data published before 2005.…”

“…Therefore, at r.t., dichloromethane (DCM, which is believed to remain as a liquid under 19–20 kbar pressure), 7,8 tetrahydrofuran (THF, under 16 kbar), 9,10 and acetonitrile (MeCN, under 15 kbar) 11 are the most suitable solvents for higher-pressure reactions. Less frequently, toluene (PhMe, 22 kbar), 12 methanol (MeOH, 16 kbar), 9 and others are used as media for hyperbaric experiments. In everyday laboratory practice, however, DCM is the most common solvent used for work under ultra-high-pressure conditions.…”

High-Pressure Cycloaddition Reactions in the Synthesis of Biologically Relevant Heterocycles

“…Jurczak has shown that 3,4-dimethoxyfuran 35 is a more active diene than furan, and employed in the synthesis of dimethoxycantharidin 41 [24]. Its higher reactivity overcomes the low reactivity of dimethyl maleic anhydride and high pressure cycloaddition with 35 could be achieved under 22 kbar at room temperature (Scheme 10).…”

The stereochemical course of the high-pressure reaction of 2,5-dialkylfurans with diethyl mesoxalate

“…Studies shown below, carried out using model compounds 4, 5, and 6 (Scheme II), provided the further evidence for the mechanism and for the place of attack of acid catalyst. Substitution in substrates 4, 5, and 6 occurs predominantly in the ethyl (7), isopropyl (9), or benzyl group (11) as compared with that in the methyl group. This high regioselectivity can be useful in the synthesis of various furan derivatives.…”

“…Mixture of products 11 and 12: colorless oil; IR (neat) v 3460, 2980,1735,1600,1550,1450,1210, 780,690 cm"1; NMR (CDC13) 7.50-7.00 (m, 5 ), 6.02 (m, 1 H), 5.85 (m, 0.43 H), 5.78 (m, 0.57 H), 5.00 (s, 0.57 ), 4.40-4.00 (m, 5 H), 3.87 (s, 0.86 H), 3.28 (s, 0.86 ), 2.20 (s, 1.71 ), 1.40-1.00 (m, 6 H). Anal.…”