Diels−Alder Reaction of 2-Amino-Substituted Furans as a Method for Preparing Substituted Anilines

Abstract

5-Amino-2-furancarboxylic acid methyl ester undergoes a facile Diels−Alder cycloaddition with a variety of dienophiles to afford ring-opened cycloadducts that are readily dehydrated using BF3· OEt2 to give polysubstituted anilines. In each case, the cycloaddition proceeds with high regioselectivity, with the electron-withdrawing group being located ortho to the amino group. The most favorable FMO interaction is between the HOMO of the furanamine and the LUMO of the dienophile. The atomic coefficient at the ester carbon of the furan is larger than that at the amino center, and this nicely accommodates the observed regioselectivity. The [4 + 2]-cycloaddition of N-(5-nitrofuranyl)morpholine with methyl vinyl ketone affords a mixture of three phenols. One of the phenols is derived from a Diels−Alder reaction followed by nitro group ejection and subsequent aromatization. The remaining two phenols are the result of cleavage of the initially formed oxabicyclic intermediate with concomitant migration of the nitro group. The mild reaction conditions with which furan-2-carbamic acid tert-butyl ester undergoes Diels−Alder cycloaddition with N-phenylmaleimide allow for the ready isolation of the initial oxybridged cycloadduct.

Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of d-glutamic acid

“…The overall yield of this approach was very low (13%), which was mostly due to the poor conversion of 17 to 18 in the first reaction step. The title 2,4-disubstituted aniline 12i was therefore synthesised using a different approach, starting from commercially available methyl 2-amino-5-furoate (20) and methyl acrylate, following a literature procedure [40]. After DielseAlder reaction in the first step the aminosubstituted 7-oxabicyclo[2.2.1]heptene 21 was spontaneously converted to substituted aniline 22.…”

“…Method 1. Dimethyl 4-aminoisophthalate (12i) [40]. To a solution of compound 19 (300 mg, 1.00 mmol) in MeOH (15 mL), 10% Pd-C (30 mg) was added, and the mixture was hydrogenated for 10 h at room temperature.…”

“…Mp: 126.5e127.0 C (lit. [40] The target compounds were prepared from sulfonyl chlorides 27 and 28 in two consecutive steps; these were synthesised from the appropriate starting materials following literature procedures [34], and from commercially available or synthesised aromatic or cyclic aliphatic amines 12aei.…”

Diels - Alder Reactions of 3-Furylamines in Organic and Aqueous Solvents

“…Ab initio molecular-orbital studies suggest that the presence of an amino group on the furan ring has a destabilizing effect on the aromaticity of furan [16] , as well as producing an increase in HOMO energy levels [12] . Both effects contribute to an increase in reactivity towards pericyclic reactions and promote exclusive selectivity in regiochemical outcomes.…”

“…N-3'-furylbenzamide and 3-methylthiofuran [7,8] undergo facile cycloaddition with monoactivated dienophiles, and Schlessinger et al have demonstrated the preparation of oxabicycloheptanone adducts from chiral 3-furylamines for the construction of (+)-cyclophellitol [9,10] . 2-Aminofurans have also been prepared by Padwa et al and used in the preparation of substituted anilines and phenols [11,12] .…”