The Synthesis and Base-Induced Breakdown of Triaryl 1,4-Oxathiins-An Experimental and DFT Study

Abstract

1,4-Oxathiins are valued for a breadth of bioactivities and are known commercial fungicides. This article explores a novel preparation of 2,3,6-trisubstituted 1,4-oxathiin-S,S-dioxides via the reaction of benzyl 1-alkynyl sulfones and aryl aldehydes under basic conditions. A total of 20 examples possessing exclusively a trans arrangement of the 2,3-diaryl substituents are exhibited; the products demonstrate a variation of functional groups on the aryl ring attached to the heterocyclic ring system. The preparation is hindered by the base sensitivity of the products, and a ring-opened by-product typically contaminates the reaction mixture. A DFT assessment of the overall system includes a lithium counterion and offers possible pathways for the incorporation of the aldehyde, the cyclization step and the requisite proton transfers. In addition, the DFT work reveals options for the ring opening chemistry. It appears the trans 2,3-diaryl selectivity is set during the cyclization stage of the reaction sequence. The practical work uncovers a new reaction pathway to create a family of novel 1,4-oxathiin-S,S-dioxides whereas the computational work offers an understanding of the structures and possible mechanisms involved.

Keywords: DFT; computational chemistry; cyclization; mechanism; oxathiin; sulfone; α-sulfonyl anion.

Figure 1

(A) Selected 1,4-oxathiane heterocycles. (B) Mechanistic conception for 1,4−oxathiin formation. (C) Example of trans-(±)-2,3-dihydro-2,3,6-triaryl-1,4-oxathiin, 4,4-dioxide formation.

Scheme 1

Probable mechanism for oxathiin formation and breakdown.

Figure 2

Optimized geometries of lithiated sulfone structures (8_a–c). Colors: gray = C; off-while = H; red = O; yellow = S; mauve = Li

Figure 3

Computed structures for the addition of lithiated benzyl sulfones 8_a/b to benzaldehyde. ‘a’ series represents one of four cis addition modes. ‘d’ series represents one of four trans addition modes.

Figure 4

Energy profile for aldehyde addition and eventual cis and trans oxathiin synthesis.

Figure 5

Interconversion of matched aldehyde addition products 9_d and 9_f through C3-S bond rotation and lithium repositioning.

Figure 6

Optimized geometries of reactants, transition states and products of the cyclization process leading to cis and trans oxathiin formation.

Figure 7

Potential Energy surfaces for proton transfer and ring opening pathways of cis- and trans-oxathiin anions. Energy entries for species 9 and 10 introduced in Figure 4 are repeated here for context.