Conformationally Constrained Oxides of 1,3‐Dithiane: Synthesis and NMR Spectroscopic Investigations

Abstract

Conformationally constrained derivatives of 1,3‐dithianes (5‐tert‐butyl‐ and 4,6‐dimethyl‐1,3‐dithiane and dithiadecalin) have been oxidised with various oxidants to yield axial and equatorial sulfoxides, disulfoxides and sulfones. Axial sulfoxides were prepared by nucleophilic hydroxide addition to the corresponding 2‐alkylidene derivatives with subsequent retro‐aldol‐type elimination. The reaction outcome is related to the relative energies of the derivatives, as demontstrated by DFT calculations. The NMR spectroscopic data of the compounds obtained were analysed to identify 4J couplings. It was found that only 4J W couplings can be observed regardless of whether there is an axial or an equatorial sulfoxide, sulfide or sulfone group present in between the respective C–H moieties. A previously postulated γ‐gauche effect of axial sulfoxides (but not of equatorial sulfoxides or sulfones) leading to the shielding of carbon atoms is not unambiguously supported by the NMR spectroscopic data of conformationally fixed derivatives.

Oxidation of Dithia Compounds: Comparative Experimental and Theoretical Studies on 1,3‐Bis(methylthio)propane, Bis(methylthio)methane, and meso‐4,6‐Dimethyl‐1,3‐dithiane

“…15 : R f =0.6 (CH 2 Cl 2 /MeOH, 20 : 1); 1 H NMR (500 MHz, DMSO‐d 6 ): δ =1.10 (d, 3 J =6.9 Hz, 3 H, CH 3 ), 1.27 (d, 3 J =6.9 Hz, 3 H, CH 3 ), 1.72 (ddd, 2 J =14.8 Hz, 3 J =12 Hz, 3 J =11.8 Hz, 1 H, 5‐H ax ), 2.26 (dt, 2 J =14.8 Hz, 3 J =2.5 Hz, 1 H, 5‐H eq ), 2.81 (ddd, 3 J =12.2 Hz, 3 J =6.9 Hz, 3 J =2.3 Hz, 1 H, 4‐H), 3.16 (ddd, 3 J =11.4 Hz, 3 J =6.9 Hz, 3 J =2.4 Hz, 1 H, 6‐H), 3.97 (d, 2 J =12.3 Hz, 1 H, 2‐H ax ), 4.15 (d, 2 J =12.3 Hz, 1 H, 2‐H eq ). The 1 H NMR data are in full agreement with published data [2f] . 17 : R f =0.38 (CH 2 Cl 2 /MeOH, 20 : 1); 1 H NMR (300 MHz, DMSO‐d 6 ): δ =1.28 (d, 3 J =6.9 Hz, 6 H, 2×CH 3 ), 1.30–1.38 (m, 1 H, 5‐H ax ), 2.23 (dq, 2 J =16.8 Hz, 3 J =2.9 H, 1 H, 5‐H eq ), 3.11 (ddd, 3 J =12.3 Hz, 3 J =6.9 Hz, 3 J =2.6 Hz, 2 H, 4‐H, 6‐H), 4.32 (dd, 2 J =9.8 Hz, 4 J =0.9 Hz, 1 H, 2‐H ax ), 4.97 (d, 2 J =9.8 Hz, 1 H, 2‐H eq ).…”

“…17 : R f =0.38 (CH 2 Cl 2 /MeOH, 20 : 1); 1 H NMR (300 MHz, DMSO‐d 6 ): δ =1.28 (d, 3 J =6.9 Hz, 6 H, 2×CH 3 ), 1.30–1.38 (m, 1 H, 5‐H ax ), 2.23 (dq, 2 J =16.8 Hz, 3 J =2.9 H, 1 H, 5‐H eq ), 3.11 (ddd, 3 J =12.3 Hz, 3 J =6.9 Hz, 3 J =2.6 Hz, 2 H, 4‐H, 6‐H), 4.32 (dd, 2 J =9.8 Hz, 4 J =0.9 Hz, 1 H, 2‐H ax ), 4.97 (d, 2 J =9.8 Hz, 1 H, 2‐H eq ). The 1 H NMR data are in full agreement with published data [2f] …”

“…Oxidations of the parent 1,3‐dithiane 28 have already been investigated previously, [2f,28] where the preferential formation of equatorial monosulfoxide 29 and in the further course of trans bissulfoxide 31 with NaIO 4 has been explained by favorable dipole effects (Scheme 3). [28a] Furthermore, it has already been mentioned that equatorial sulfoxide 29 is somewhat more stable than its axial isomer 30 [2f] . In fact we calculated dimethylated monosulfoxide 15 to be not more than 1.8 kJ/mol more stable than its axial isomer 16 .…”

“…General . Compound 2 was purchased and dithianes 3 , [33] 16 , 18 , 20 , 21 , and 23 [2f] were synthesized according to published procedures. Technical solvents (acetone, CH 2 Cl 2 , and n ‐pentane) were distilled prior to use.…”

Dependence of Stereoelectronic and Charge Effects on pKa Values of 1,3‐Dithiane‐Derived Sulfides, Sulfoxides, and Sulfones: An Experimental and Computational Investigation

“…Whereas 25 can be expected to be in a conformation (and have a stability) that is similar to that of 5 (cf. Ref 34…”