Application of benzo[d]thiazoyl(BT)sulfonyl group as traceless directing group in organic synthesis

Malonic acid esters are standard commonly employed reagents in organic synthesis and are generally used to introduce –CH2COOR or its derivative into targeted molecules. In general, malonic diesters might be successfully used as reagents in various synthetic transformations as e.g. Knoevenagel and Claisen condensation or 1,4-addition to unsaturated carbonyl compounds. The unique structure of malonates (1,3-dicarbonyl motive) that allows to nucleophile (enolate) to be formed under mild reaction conditions (pK = 15-16 (in DMSO)) is however counterbalanced by the difficulty related to redundant carboxylic group removal. In general rather hard reaction conditions have to be used. In context of our research plans, we become interested in the use of malonates as reagents for Mitsunobu reaction. Disappointingly, after brief literature search, we figured out that only modified malonate diesters (e.g. perfluorated dialkyl malonates) can be successfully used under the Mitsunobu reaction conditions. And even in these cases, only activated alcohols (e.g. allylic alcohols) could be used as substrates. As a consequence, we decided to focus our efforts on design of new malonate diester – reagent equivalent that would react under Mitsunobu-type reaction conditions. Additionally, obtained Mitsunobu reaction product should easily release the directing group, preferentially under very mild reaction conditions that should tolerate range of functional groups. To successfully accomplish this task, we decided to replace one of the malonic diester carboxylates with a new “traceless” directing group – benzo[d]thiazoyl (BT) sulfonyl group. We opt for this group, because it should not only increase the acidity of hydrogen atoms placed  to carbonyl group (expected pK = 12-13), but also should be ease to be removed under radical, electrophilic, nucleophilic or reductive conditions. The remaining a-carbonyl sulfinate or sulfinic acid residue should then spontaneously release SO2 group and yield the desired –CH2CO2R chain. Fortunately, our expectations were fulfilled and we were able to develop set of conditions under which primary and secondary alcohols can be used as alkylating agents of b-carbonyl BT-sulfones to achieve, in two steps protocol, stereoselective a alkylation of acetic acid derivatives.