β-Sulfinyl α,β-Unsaturated Carbonyl Compounds from Enantiomerically Pure Sulfenic Acids

Abstract

The addition of enantiopure sulfenic acids to oxoalkynes constitutes a new and efficient methodology for the synthesis of beta-sulfinyl alpha,beta-unsaturated carbonyl compounds. Sulfenic acids 3 and 4 were generated by thermolysis of suitable precursors and trapped in situ by oxoalkynes 5, affording (R(S),E)- and (S(S),E)-3-alkylsulfinyl-1-phenyl-2-propen-1-ones, 4-alkylsulfinyl-3-buten-2-ones, and 3-[(1S)-isoborneol-10-sulfinyl]-2-propenoates 6 and 7 in good yields and in enantiomerically pure form after simple column chromatography. (R(S),E)-3-[(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen-1-one (6(R)a) was involved as a heterodiene in inverse-electron-demanding Diels-Alder reactions with readily available electron-rich dienophiles 14 and 15, corroborating in each case the sulfinyl auxiliary capability in controlling the stereochemical outcome of these cycloadditions. Furthermore, the addition of methylmagnesium iodide to the carbonyl moiety of 6(R)a demonstrated that the chiral sulfur atom exerts a remote stereocontrol in this reaction if assisted by the hydroxy group being part of the isoborneol substituent.

Sulfinyl Homo- and Hetero-Dienes from Sulfenic Acids: An Approach Towards Six-membered Nitrogen Heterocycles in Enantiomerically Pure Form

“…In all the synthesized isoborneol sulfoxides 6-8, 15-21, 23, 24, 29, 31, 32 this H-2¢ resonance appears as a doublet of doublets, sometimes further spin-spin coupled with the hydroxy proton, in the range 4.0-4.2 ppm. The same resonance is clearly shielded (3.71 ppm) in tricyclic derivative 25 where the corresponding proton is identified as H-1, and analogous trend was observed in structurally related compounds such as 26, 13a 27, 6 and 28. 13b At the same time the C-2¢ resonance is observed in the range 76.4-77.2 for sulfoxides 6, 8, 15, 18, 20, 21, 23, 24, 31, 32 but it is deshielded to 85.1 ppm in compound 25, where the corresponding carbon nucleus is identified as C-1.…”

“…The synthetic approach, shown as pathway a in Scheme 2 and followed at first, suffered the limitation of the desired compounds being formed in low yields, and this restriction induced us to cover pathway b whose key step consisted of the addition of a sulfenic acid to a carbonyl compound, positively corroborated by our previous studies. 6 Thermolysis of cyanoethylsulfinylisoborneols 9 in the presence of phenylpropargyl aldehyde (14) afforded 3-[(1S)-isoborneol-10-sulfinyl]-3-phenyl-2-propenals 17 and 18 and 2-[(1S)-isoborneol-10-sulfinyl-3-phenyl-2propenals 19 and 20 in a 43:40:11:6 ratio and 73% total yield (Scheme 4). Despite the observed loss of stereoselectivity, since the two sulfur epimers 17 and 18 were obtained in almost the same percentages, and an analogous ratio was measured between 19 and 20, the addition of sulfenic acid 10 to aldehyde 14 showed an increased regioselectivity (83:17) and a much better total yield.…”

“…fused oxathia heterocycles 26-28 ( Figure 1). 6,13 Their structures are easily recognizable on the basis of their NMR data. In particular the resonance of the geminal proton to isoborneol oxygen atom is clearly indicative of cyclization involving the hydroxy group.…”

“…On the other hand, the facile access to high yields of enantiomerically pure b-sulfinyl a,b-unsaturated carbonyl compounds suggested their use as heterodienes in inverse electron-demanding DA reactions, giving an alternative access to enantiopure pyranoid systems (see, for instance, the synthesis of 3 in Scheme 1). 6…”

Synthesis of chiral vinylic sulfoxides by Pd-catalyzed asymmetric sulfinylzincation

“…Aversa and co-workers reported an asymmetric addition of a sulfenic acid to unsaturated bonds. 2 However, the stereoselectivity of sulfinylation was not sufficiently high. The asymmetric addition of a chiral sulfenic anion has not hitherto been investigated, to the best of our knowledge.…”