Titanocene Dichloride as a Convenient Catalyst for the Diastereoselective Oxidation of 2-Substituted 1,3-Dithianes and 1,3-Dithiolanes

Abstract

Cp 2 TiCl 2 is an efficient catalyst for the diastereoselective mono-oxidation of 2-substituted 1,3-dithianes and 1,3-dithiolanes by tert-butyl hydroperoxide; comparable stereoselectivities and better yields than Ti(i-PrO) 4 were obtained. Activities are similar, provided activated 4Å molecular sieves are present in the titanocenepromoted process. Furthermore, Cp 2 TiCl 2 is a more moisture stable compound than Ti(i-PrO) 4 and therefore can be used in catalytic amounts of 1 mol%.The d 0 transition metal/alkyl hydroperoxide system has been extensively used for the oxidation of a number of organic compounds, in particular alkenes and thioethers. 1 In several instances, fairly good diastereoselectivities can be obtained in the oxidation of allylic alcohols 2 and thioethers 3 containing a stereogenic center. The level of the stereoselectivity, however, is dependent on the metal catalyst and the substrate structure.Ti(IV) alkoxides are commonly employed as catalysts in the diastereo-2b,4 and enantioselective 5 epoxidation of allylic alcohols as well as in the enantioselective oxidation of thioethers. 6 Surprisingly, cyclopentadienyl Ti(IV) compounds, despite their great availability and wide employment as catalysts in many homogeneous processes, 7 have been scarcely used in these oxidation reactions. 8 We have recently shown the applicability of titanocenes such as Cp 2 TiCl 2 , CpTiCl 3 and bis(cyclopentadienyl)titanium (IV) bis(trifluoromethanesulfonate) [Cp 2 Ti(OTf) 2 ] in the diastereoselective epoxidation of allylic 9 and bishomoallylic 10 alcohols and in the enantioselective sulfoxidation 11 using tert-butyl hydroperoxide (TBHP) as oxidant; the catalytic activity is markedly enhanced in the presence of activated 4Å molecular sieves.As an extension of our work, we became interested in the diastereoselective oxidation of dithianes. A great deal of data is avalaible in the literature on the oxidation of racemic 2-substituted 1,3-dithianes and 1,3-dithiolanes as models of cyclic thioethers. Except for enzymatic reactions, 12 d 0 transition metal/alkyl hydroperoxides proved to be the most stereoselective oxidizing systems for this type of substrates. 13 However, the chiral Kagan and Modena catalyst, a Ti(i-PrO) 4 /(+)-diethyl tartrate [(+)-DET] modified system, 13a,b,14,15 has been mostly used in stoichiometric amount to achieve a diastereo-and enantioselective process. The diastereoselectivity is merely associated with facial discrimination, whereas the enantioselectivity is a result of both facial selectivity and selection between the two enantiotopic sulfur atoms. In order to perform a diastereoselective transformation, a simple achiral transition-metal catalyst can be employed.Very few systematic reports 16 have appeared concerning the use of an achiral reagent for the diastereoselective oxidation of thioethers. Indeed, a catalytic (using minimal amount of catalyst) process would be highly desiderable and the use of cheap, safe and stable catalysts should be highly preferable.In the present work, we compare s...

Enantioselective Synthesis of Sulfoxides: 2000−2009

“…339 Cp 2 TiCl 2 was also found to be an efficient catalyst of the conversion of achiral 2-substituted-1,3-dithianes and 1,3-dithiolanes 180, 292, and 327-329. 340 Using TBHP as oxidant and 4 Å molecular sieves, 2-phenyl-1,3-dithiane was oxidized in 86% yield and 96% de. A similar or lower preference for the trans diastereomer was observed for other substrates.…”

“…In certain titanium-catalyzed oxidations, the addition of 4 Å molecular sieves has a beneficial effect on the yield and stereochemical outcome. 28,92,221,241,340 However, there are only a few examples of the application of heterogeneous catalysts in the preparation of nonracemic sulfoxides. Preliminary studies performed on sulfide oxidation with urea-H 2 O 2 catalyzed by cinchonine and cinchonidine salts with a Keggin-type structure heteropolyacid suggested the possibility of applying this system for the enantioselective synthesis of sulfoxides.…”