Interplay of Structure and Reactivity in a Most Unusual Furan Diels-Alder Reaction

Abstract

Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2-propenoate reacts rapidly and in high yield with furan and a range of substituted furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N-diethylcarbamoyloxy)-2-propenoate fails to react at all under the same conditions. These reactions have been explored using density functional theory (DFT) calculations. They reveal a highly polar transition state, which is stabilized by the Lewis acid catalyst SnCl(4) and by polar solvents. In the presence of both catalyst and solvent, a two-step reaction is predicted, corresponding to the stepwise formation of the two new carbon-carbon bonds via transition states which have similar energies in all cases. Our experimental observations of the lack of reaction of the non-fluorinated dienophile, the stereochemical outcomes, and the rate acceleration accompanying furan methylation are all well predicted by our calculations. The calculated free energy barriers generally correlate well with measured reaction rates, supporting a reaction mechanism in which zwitterionic character is developed strongly. An in situ ring opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3-difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H-benzo[1,3]dioxole-3a-carboxylate by a Curtin-Hammett mechanism, has also been examined. Substantial steric opposition to Lewis acid binding prevents carbonate formation from 2-substituted furans.

Fluorinated enol ethers: their synthesis and reactivity

“…82a,140 DFT calculations allowed to rationalize the high reactivity of difluoroenoate 106 in the tin-catalyzed reaction with furan in comparison to its non-fluorinated analogue. 141 As for [3,3]-rearrangement reactions, the higher stability of the sp 3 -hybridized CF 2 group compared to the sp 2 -hybridized CF 2 Posner also reported the Diels-Alder reaction of 104c with 3-methoxycarbonyl-2-pyrone under high pressure conditions (Scheme 119). 142 Monofluorinated derivatives were also used as dienophiles as illustrated by the reaction of 110 with various dienes under thermal conditions.…”

Addition Reactions: Cycloaddition

“…In the presence of SnCl 4 and polar solvents, a twostep reaction was predicted. 93 The catalytic effect of Lewis acids in the Diels-Alder reaction between methylacrolein derivatives and cyclopentadiene can be explained through the analysis of the electrophilicity effect of the regents and the molecular structure of the corresponding transition structures. 94 The chiral auxiliary (85), derived from levoglucosenone, has been used as a chiral template in the Diels-Alder reaction of the corresponding acrylic ester derivative with cyclopentadiene.…”

“…The key intermediate (94), in the projected synthesis of the antibiotic branimycin, was prepared by the transannular Diels-Alder reaction of the macrocyclic tetraene (93) in 70% yield (Scheme 24). 105 The hypervalent iodine-mediated oxidative dearomatization-Diels-Alder cascade was investigated as a means of preparing the [2.2.2]bicyclic core of the natural product tashironin.…”

Recent progress in the use of fluoroorganic compounds in pericyclic reactions

“…58 While 34a is a reactive dienophile in the presence of a tin(IV) catalyst, 34b remains unchanged, even after prolonged reaction (Scheme 16A). 56 To explain the differing reactivities of 34a and 34b, the simplified molecules 35a and 35b were used in computations (Scheme 17A).…”