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. 2018 Feb 16;83(4):1948-1958.
doi: 10.1021/acs.joc.7b02896. Epub 2018 Jan 26.

Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes

João R Vale  1   2 , Tatu Rimpiläinen  1 , Elina Sievänen  3 , Kari Rissanen  3 , Carlos A M Afonso  2 , Nuno R Candeias  1
Affiliations

Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes

João R Vale et al. J Org Chem. .

Abstract

The autoxidative condensation of 2-aryl-2-lithio-1,3-dithianes is here reported. Treatment of 2-aryl-1,3-dithianes with n-BuLi in the absence of any electrophile leads to condensation of three molecules of 1,3-dithianes and formation of highly functionalized α-thioether ketones orthothioesters in 51-89% yields upon air exposure. The method was further expanded to benzaldehyde dithioacetals, affording corresponding orthothioesters and α-thioether ketones in 48-97% yields. The experimental results combined with density functional theory studies support a mechanism triggered by the autoxidation of 2-aryl-2-lithio-1,3-dithianes to yield a highly reactive thioester that undergoes condensation with two other molecules of 2-aryl-2-lithio-1,3-dithiane.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1
Scheme 2
Scheme 2
For reaction conditions see footnote a, Table 1. LDA as base.
Scheme 3
Scheme 3
For reaction conditions see footnote a, Table 1. Isolated yields. Unreacted dithiane 4 was isolated as the major species. 2-(n-Hexyl)-1,3-dithiane was also isolated in 23%.
Scheme 4
Scheme 4
Scheme 5
Scheme 5
Figure 1
Figure 1
Free energy profile (PBE0) for deterioration of lithium alkoxide and reaction with 2-phenyl-2-lithio-1,3-dithiane, and mechanistic representation. Optimized structures of minima and transition states are presented with bond distances and Wiberg indexes (in italics) for the more relevant bonds. Free energies values are presented in kcal/mol, referring to the initial intermediate A.
Figure 2
Figure 2
Free energy profile (PBE0) for nucleophilic condensation of α-disubstituted ketone with 2-phenyl-2-lithio-1,3-dithiane and mechanistic representation. Optimized structures of minima and transition states are presented with bond distances and Wiberg indexes (in italics) for the more relevant bonds. Free energies values are presented in kcal/mol, referring to the initial intermediate A from Figure 1.
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