The hetero-Diels–Alder addition of sulfur dioxide: structure of the first crystalline sultine. Quantum calculations on the conformations of 6-fluoro-3,6-dihydro-1,2-oxathiine 2-oxides

Abstract

The hetero-Diels-Alder addition of sulfur dioxide to (E)and (Z)-4-(fluoromethylidene)-3-methylene-2,3-dihydronaphthalene follows the endo Alder rule. The first example of a crystalline sultine has been obtained. In agreement with high level quantum calculations, (1SR,3SR)-1-fluoro-1,4,5,6-tetrahydronaphtho[2,1-d][1,2]oxathiine 3-oxide adopts a sofa conformation in its ground state.

The Hetero-Diels-Alder Addition of Sulfur Dioxide to 1-Fluorobuta-1,3-dienes: The Sofa Conformations Preferred by 6-Fluorosultines (6-Fluoro-3,6-dihydro-1,2-oxathiin-2-oxides) Enjoy Enthalpic and Conformational Anomeric Effects

“…Assuming that the homoallylic coupling constants 5 J (H3,F) follow a relationship similar to that found for 5 J (H3,H6)=(5 Hz)(sin θ ) 2 (sin θ ′) 2 in cyclohexenes, in which θ and θ ′ are the angles that H3 and H6 make with the C1,C2,C3,C4 plane,19 the data suggest that one of the two protons H3 of 20 always resides in a pseudo‐equatorial position ( 5 J (H eq 3,F)<2 Hz) and the other in a pseudo‐axial position ( 5 J (H ax 3,F)=7.9 Hz) and this independently of the relative configuration of 20 , which can be either cis or trans. These observations imply, therefore, that cis ‐ 20 is either in a sofa conformation ( cis ‐ 23 (So)), as predicted by calculations,11 or exists as an equilibrium between this conformer, the boat ( cis ‐ 20 (B)) and the pseudo‐chair conformer ( cis ‐ 20 (C)), as shown in Scheme . The NMR data of 20 are also consistent with the trans isomer adopting the sofa conformation or existing as an equilibrium of conformers trans ‐ 20 (So)= trans ‐ 20 (B)= trans ‐ 20 (C).…”

“…At −40 °C, cis ‐ 9 isomerizes into the more stable trans isomer trans ‐ 9 . Above −30 °C, the latter decomposes, and no trace of the corresponding sulfolene 10 (Scheme ) could be detected 11. Diene ( E )‐ 8 is less reactive than ( Z )‐ 8 .…”

“…The structures of 20 – 22 were deduced from 1 H NMR and 13 C NMR data of the crude reaction mixtures and by comparison with data reported for derivatives cis ‐ 9 (see below) and trans ‐ 9 11. Because of the presence of unreacted ( Z )‐ 11 and of polymeric material, selective TOCSY experiments were necessary to obtain the 1 H NMR spectra of sultines 20 and 21 .…”

“…In square parenthesis the G3 calculated energies relative to SO 2 + ( E )‐ 11 . [a] These conformers are not energy minima by calculations11 (see Scheme ).…”

Stereoselective Carbonyl Olefination with Fluorosulfoximines: Facile Access to Z or E Terminal Monofluoroalkenes

“…Terminalmonofluoroalkenesareofvitalimportancebecause they are not only widely used in the synthesis of fluorinecontaining compounds, [1,2] but also have great relevance to material science [3] as well as the design of mechanism-based enzyme inhibitors (Scheme 1, A-C) [4] and homeostasis regulators (Scheme 1, D) [5] owing to the ability of fluorine to modulate bioactivity. [6] Moreover, the E and Z stereoisomers of monofluoroalkenes often possess significantly different bioactivities; one notable example is the BPAO inhibitor B, which is 10-fold more effective than its E isomer on the basis of IC 50 values.…”