Final Report Summary - ALCLASS (Application of Lithiated Carbamates to the Asymmetric Synthesis of Sulfolipid-I)
In planning organic syntheses, disconnections are most often made adjacent to functional groups, which assist in C–C bond formation. For molecules devoid of obvious functional groups this approach presents a problem, and so functionalities must be installed temporarily and then removed. Here we present a traceless strategy for organic synthesis that uses a boronic ester as such a group in a one-pot lithiation–borylation–protodeboronation sequence. To realize this strategy, we developed a methodology for the protodeboronation of alkyl pinacol boronic esters that involves the formation of a boronate complex with a nucleophile followed by oxidation with Mn(OAc)3 in the presence of the hydrogen-atom donor 4-tert-butylcatechol. Iterative lithiation–borylation–protodeboronation allows the coupling of smaller fragments to build-up long alkyl chains. We employed this strategy in the synthesis of hydroxyphthioceranic acid, a key component of the cell-wall lipid of the virulent Mycobacterium tuberculosis, in just 14 steps (longest linear sequence) with full stereo control.
The synthesis of primary and secondary pinacol boronic esters via lithiation–borylation of carbamates and benzoates with pinacol borane is described. This new protocol enables the highly selective synthesis of enantioenriched and geometrically defined boronic esters that cannot otherwise be accessed by alternative methodologies.
The synthesis of primary and secondary pinacol boronic esters via lithiation–borylation of carbamates and benzoates with pinacol borane is described. This new protocol enables the highly selective synthesis of enantioenriched and geometrically defined boronic esters that cannot otherwise be accessed by alternative methodologies.