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

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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“…NMR spectra were recorded with Varian Mercury 300 MHz or Jeol ECZR 500 instruments using CDCl 3 as solvent and calibrated using tetramethylsilane as internal standard. Chemical shifts (δ) are reported in ppm referenced to the CDCl 3 residual peak (δ 7.26) or TMS peak (δ 0.00) for 1 H-NMR and to CDCl 3 (δ 77.16) for 13 C-NMR. The following abbreviations were used to describe peak splitting patterns: s = singlet, d = doublet, t = triplet, m = multiplet.…”

“…Compounds 1-4 were prepared and characterized as reported elsewhere [13], through autoxidative condensation of 2-aryl-2-lithium-1,3-dithianes, prepared from treatment of 2-aryl-1,3-dithianes with n-BuLi followed by air exposure.…”

“…1 H NMR (500 MHz, CDCl 3 ) δ ppm 9.02 (s, 3H), 8.51-8.48 (m, 6H), 7.76-7.67 (m, 6H), 7.62 (dd, J = 8.4, 2.0 Hz, 1H), 7.25-7.08 (m, 5H), 5.56 (s, 1H), 3.86 (s, 3H), 3.85 (s, 3H), 3.83 (s, 3H), 3.31 (dd, J = 13.3, 11.2 Hz, 2H), 2.79 (dd, J = 14.3, 3.6 Hz, 2H), 2.70-2.58 (m, 4H), 2.14-2.11 (m, 1H), 1.98-1.91 (m, 1H), 1.86-1.81 (m, 2H). 13…”

“…Some of us have recently reported the unprecedented autoxidative condensation of 2-aryl-2lithio-1,3-dithianes (Scheme 1) [13]. The result of such transformation was a small library of highly functionalized molecules containing α-thioether ketones and orthothioesters functionalities, among others.…”

Reactions of 2‐Aryl‐1,3‐Dithianes and [1.1.1]Propellane

“…[14] Recent reports demonstrate new and unexpected reactivity of 1,3-dithianes,s uch as for the synthesis of pyridines and photochemical addition to electrophiles. [15] Anotable case of new reactivity of dithianes is the Smith groupsdevelopment of anion-relay chemistry using 2-silyl-1,3-dithianes. [16] 2-Aryl-1,3-dithianes could be used as pronucleophiles for palladiummediated arylation [17] and allylic substitution [18] in ad eprotonative cross-coupling process.T oe nable synthetic access to BCP ketones and to explore new reactivity of 1,3-dithianes, we describe herein the addition of 2-aryl-1,3-dithianes to [1.1.1]propellane,a nu nprecedented transformation which furnishes BCP analogues of avaluable pharmacophore.BCP dithianes are readily deprotected to the corresponding ketones.W ea lso demonstrate that these BCP dithianes are readily transformed to geminal difluoromethanes and esters.…”