Applications Of A-oxo Ketenedithioacetals As Odorless Thiol Equivalent In Organic Synthesis

Thioacetals have been extensively investigated as carbonyl protection groups and versatile intermediates in the synthesis of multi-functional complex molecules and natural products. Generally, thioacetals are prepared by the condensation of carbonyl compounds with thiols or dithiols employing various acidic catalysts.Unfortunately, the conventional methods suffer from the use of volatile, foul-smelling, low molecular weight thiols that can lead to serious safety and environment problems. To resolve these drawbacks, some attempts have been made to develop odorless substitutes for these obnoxious thiols. As a result, a range of, odorless or faint smell thiols have been prepared by increasing the alkyl chain length of thiol or introducing a trialkylsilyl group into the benzene ring of benzyl mercaptan and benzenethiol. Alternatively, incorporation of 1,3- propanedithiol functions within linear or cross-linked co-polymeric reagents have been realized and applied in organic synthetic chemistry. However, the multistep process of preparation, the high cost of catalysts, and thej toxicity of some precursors limit the further utilization of such thiol reagents or their equivalents. From the green chemistry point of view, the development of practically odorless and less volatile substitutes for such thiols is still of great importance and necessity. The organic reactions in water without the use of any organic solvent can also benefit from that water is an easily available, cheap, safe and environmentally benign solvent. Later on, extensive work has revealed that a variety of organic reactions including Mukaiyama aldol reaction, allylation reactions, Diels-Alder reaction, Michael reactions, Manich-type reactions and even dehydration reaction can be realized in the presence of various catalysts such as inverse phase-transfer catalysts and surfactant-type Lewis or Bronsted acids in water.Combining with the special properties of a-oxo ketenedithioacetals, we have succeeded in exploring a new kind of reagents instead of thiols. Moreover, which have been successfully applied on protecting the carbonyl groups of aldehydes/ketones and Michael addition reaction in water and solvent-free conditions. This work mainly based on the following three aspects:1. A clean, facile and practical synthesis of. a-oxo ketene-(S,S)-acetals has been developed based on the reaction of 6-dicarbonyl compounds with carbon disulfide and alkyl halide catalyzed by tetrabutylammonium bromide in the presence of potassium carbonate in water. The simple procedure, mild conditions, easy separation, high yields, and especially that in relation to the current environmental concerns, make this protocol mostattractive for academic research and practical applications.2. We describe a novel thioacetalization reaction in water in the presence of DBSA. The results demonstrate that 3-(l,3-dithian-2-ylidene)pentane-2,4-dione or 2-(l,3-dithian-2-ylidene)propane diacid is an efficient and practical thioacetalization reagent in aqueous media. Associated with mild conditions, simple procedure, high yield, and environmentally benign reagents, this novel thioacetalization provides a convenient protocol for the synthesis of thioacetals and the protection of carbonyl compounds with high chemoselectivity.3. Odorless 3-(l,3-dithian-2-ylidene)pentane-2,4-dione has been investigated as 1,3-propanedithiol equivalent in thioacetalization under solvent-free conditions. Promoted by concentrated HC1, a wide range of aldehydes and aliphatic ketones has been converted into the corresponding dithianes in high yields. Associated with mild conditions, simple procedure and high yields, the reported procedure provides a convenient and clean protocol for th^ synthesis of thioacetals and the protection of carbonyl compounds with high chemoselectivity* Moreover, we have researched the Michael addition reaction of a-oxo ketenedithioacetal^ with a., fi-unsaturated ketones.In summary, we have succeeded in exploring a new kind of reagents instead of thiols, moreover, which have been successfully applied on protecting the carbonyl groups ofj aldehydes/ketones in water and Michael addition reaction under solvent-free condition. This method is associated with some synthetic advantages, such as simple procedure, fast reaction rate, high yields and mild conditions. So these new reagents have good perspective in the field of academic research and practical applications. (...