Diastereodivergent Synthesis of 2-Ene-1,4-hydroxy Sulfides from 2-Sulfinyl Dienes via Tandem Sulfa-Michael/Sulfoxide-Sulfenate Rearrangement

Abstract

The highly diastereoselective sulfa-Michael addition of thiolates to enantiopure 2-sulfinyl dienes leads to anti or syn 2-ene-1,4-hydroxy sulfides in good yields and selectivities dependent on the reaction conditions in a diastereodivergent process. Synthetic applications of these enantiopure hydroxy sulfides by subsequent sigmatropic rearrangements have been outlined.

Base-Induced Sulfoxide-Sulfenate Rearrangement of 2-Sulfinyl Dienes for the Regio- and Stereoselective Synthesis of Enantioenriched Dienyl Diols

“…Diols 4 were transformed into methoxyphenyl acetates (MPA) for full stereochemical assignment of pure or enriched samples (Figure ). As previously documented, , diesters of 1,2-diols [( S )-MPA] displayed larger differences in H 1 chemical shifts for 6 (C 2 ( S ), Δ H 1a–1b = 0.34–0.35 ppm) than for 7 (C 2 ( R ), Δ H 1a–1b = 0.07–0.10 ppm), in H α [Δ H α1−α2 ( 6 ) > Δ H α1−α2 ( 7 )] and also H 3 in 6 appears downfield relative to 7 . Similarly, differences in chemical shifts for H 1 and H 4 in monoesters of 4b , 4e , 4i , and 4l [( S )-MPA, 6 and [( R )-MPA, 6′ ] were consistent with the stereochemistry proposed.…”

“…6, 142.4, 142.0, 130.6 (2C), 125.4 (2C), 114.6, 43.5, 33.1, 32.8, 26.2, 25.91, 25.87, 21.4 General Procedure for the Synthesis of Sulfinyl Dienes, 1. Dienes (E,Z)-1a, 18 (E,E)-1b, 21 (E,Z)-1h, 18 and (E,Z)-1k 9 were already reported.…”

“…2a In this context, during the last years, our group has developed the diastereoselective Michael-type addition to 1and 2-sulfinyl dienes (1 and 2) to generate transient allylic sulfoxides I that evolved through [2,3]-sigmatropic rearrange-ment (Scheme 1b). We have applied this tandem process intramolecularly for the stereoselective synthesis of enantiopure functionalized dihydropyrans 5 and tetrahydropyridinols 6 as well as intermolecularly for the synthesis of acyclic 2-ene-1,4-diols, 7 1,4-aminoalcohols, 8 and 1,4-hydroxysulfides 9 with a high degree of stereocontrol.…”

Stereoselective Synthesis of Highly Functionalized Structures from α‐Bromo α’‐Sulfinyl Ketones

“…Next, we focussed our attention to the creation of sulfur-carbon bonds, of considerable importance in biological processes, material science, medicinal chemistry, and synthetic methodologies. [15] For this meaning, anti-5 a and syn-5 a were successfully reacted with thiophenol, using K 2 CO 3 as the base, providing the corresponding thioether derivatives syn-11 and syn-11 in 83 and 81 % yield, respectively by an S N 2 reaction.…”

“…The reaction was run under micro‐wave irradiation in DMF at 60 °C and provided the azido derivatives anti ‐ 10 and syn ‐ 10 in 81 and 80 % yields, respectively with inversion of configuration at C‐3. Next, we focussed our attention to the creation of sulfur‐carbon bonds, of considerable importance in biological processes, material science, medicinal chemistry, and synthetic methodologies [15] . For this meaning, anti ‐ 5 a and syn ‐ 5 a were successfully reacted with thiophenol, using K 2 CO 3 as the base, providing the corresponding thioether derivatives syn ‐ 11 and syn ‐ 11 in 83 and 81 % yield, respectively by an S N 2 reaction.…”