Multistep Synthesis of Complex Boronic Acids from Simple MIDA Boronates

Abstract

Due to its sensitivity to most synthetic reagents, it is typically necessary to introduce the boronic acid functional group just prior to its utilization. Overcoming this important limitation, we herein report that air- and chromatographically stable MIDA boronates are compatible with a wide range of common reagents which enables the multistep synthesis of complex boronic acid building blocks from simple B-containing starting materials. X-ray and variable temperature NMR studies link the unique stability of MIDA boronates to a kinetic inaccessibility of the potentially reactive boron p-orbital and/or nitrogen lone pair. These findings were collectively harnessed to achieve a short and modular total synthesis of (+)-crocacin C via the iterative cross-coupling of a structurally complex, MIDA-protected haloboronic acid building block.

Amphotericin primarily kills yeast by simply binding ergosterol

“…These sensitivities can be magnified considerably when specific functional groups have been deleted from the polyene macrolide skeleton, which has previously precluded the synthesis of some targeted AmB derivatives, including C35deOAmB (29). To improve the efficiency and flexibility with which such complex small molecules can be prepared, we have recently developed a simple and modular synthesis strategy, analogous to iterative peptide coupling, in which building blocks having all of the required functional groups preinstalled in the correct oxidation states and with the desired stereochemical relationships are sequentially linked via iterative application of one mild reaction (30)(31)(32)(33)(34)(35)(36)(37)(38). Enabling this approach, we discovered that N-methyliminodiacetic acid (MIDA) is a highly effective ligand for reversibly attenuating the reactivity of a boronic acid and thereby permitting the controlled sequential assembly of bifunctional haloboronic acids (Fig.…”

Microwave-mediated synthesis of N-methyliminodiacetic acid (MIDA) boronates

“…Examples of the latter include oxidations under Jones or Swern conditions or cycloisomerization of arylethynyl MIDA boronates. 11,12 These allow for greener, multistep telescopic reactions with an in situ cleavage of the MIDA boronate, enabling a second coupling, minimising work-up and solvent usage in these one-pot processes. This is desirable in medicinal chemistry as the deployment of faster reaction times, fewer reaction steps and lower solvent volumes is desirable.…”

Direct Synthesis of 1,4‐Disubstituted‐5‐alumino‐1,2,3‐triazoles: Copper‐Catalyzed Cycloaddition of Organic Azides and Mixed Aluminum Acetylides

“…As a matter of fact, numerous examples of such a strategy have recently been reported using organoboron or organotin reagents, which shows that several synthetic transformations can be conducted on remotely embedded functional groups of these compounds. [5] If one considers the difference in electronegativity between a metal and a carbon atom as an empirical criterion for the development of functionalized organometallic compounds, as proposed by Knochel and co-workers in their seminal review on this field, [6] it is striking to see that the carbonÀaluminum bond can be located between the carbonÀ zinc and the carbonÀmagnesium bond, which are two very important classes of functional organometallic reagents. However, despite some very recent important works on the preparation and reactivity of organoaluminum compounds, [7] the development of functional organoaluminum reagents is still underinvestigated.…”