Synthesis of hydroxyphthioceranic acid using a traceless lithiation–borylation–protodeboronation strategy

Abstract

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 stereocontrol.

One-step catalytic asymmetric synthesis of all- syn deoxypropionate motif from propylene: Total synthesis of (2 R ,4 R ,6 R ,8 R )-2,4,6,8-tetramethyldecanoic acid

“…Due to the iterative nature of methyl-branched chiral center formation, these syntheses required a total of 8-17 steps. Recently, convergent strategies for the synthesis of the deoxypropionate motif have been reported to shorten the synthetic route but generation of byproducts remains unavoidable (12,13).…”

Alkali Metal Carbenoids: A Case of Higher Stability of the Heavier Congeners

“…[2,3] Similar to carbenes,metal carbenoids exhibit an ambiphilic character. [5][6][7] This limitation is mainly due to the high reactivity and thermal sensitivity of these systems.T hus, only few carbenoids,p articularly examples of the extremely reactive lithium halogen systems,h ave been isolated so far. [5][6][7] This limitation is mainly due to the high reactivity and thermal sensitivity of these systems.T hus, only few carbenoids,p articularly examples of the extremely reactive lithium halogen systems,h ave been isolated so far.…”

Asymmetric Synthesis of Deoxypropionate Derivatives via Catalytic Hydrogenolysis of EnantioenrichedZ-Ketene Heterodimers

“…5 Most synthetic strategies for deoxypolypropionates follow a linear-iterative concept, with new deoxypropionate units being successively added to a growing chain. 2,6 This approach, although conceptually simple, can lead to rather lengthy syntheses of complex molecules. Recently, some highly diastereoselective catalytic asymmetric approaches, which are not limited to iterative synthetic plans, have been introduced.…”

“…4 Aggarwal’s group has also recently demonstrated how similar deoxypropionate units may be incorporated via an iterative lithiation–borylation–protodeboronation strategy into a growing polydeoxypropionate chain. 6 …”