Formation of Complex Boronic Acids from MIDA Boronates

By: Josephine Nakhla, ChemFiles Volume 9 Article 1

Another extremely useful feature of the MIDA boronates is their compatibility with a wide range of common synthetic reagents, allowing for the elaboration of functionalized MIDA boronates to create structurally complex boronic acid surrogates. This was recently demonstrated by Burke and coworkers with the transformation of the 4-(hydroxymethyl)phenyl MIDA boronate (698105) by a variety of common oxidants and other reagents to create an array of synthetically useful MIDA boronates (Scheme 9). Even harsh reagents such as triflic acid, and Jones oxidant were well tolerated, and the MIDA boronate was left intact. In several cases, transformations can be easily reversed to yield the original 4-(hydroxymethyl)phenyl MIDA boronate.

Scheme 9 (698105)(697494)

The 4-formylphenyl MIDA boronate (697494) was further elaborated in various C-C bond-forming reactions. The results show that MIDA boronates are also compatible with Evans aldol, Horner-Wadsworth- Emmons olefination, and Takai olefination protocols. Reductive amination is also well-tolerated (Scheme 10).

Scheme 10 (697494)

The impact of the exceptional compatibility of the MIDA boronate was exhibited in the total synthesis of (+)-crocacin C starting from an acrolein MIDA boronate (Scheme 11). The MIDA boronate tolerated a Paterson aldol and diastereoselective reduction protocol to yield the diol MIDA boronate, which was purified by silica gel chromatography. The purified MIDA boronate was permethylated with Meerwein’s salt, deprotected with CAN, oxidized with Dess-Martin periodinane and subjected to Takai olefination to yield the stable, crystalline, complex MIDA boronate 9. Stille coupling of 9 with known building block 10, followed by in situ boronic acid release and cross-coupling with bromobenzene provided (+)-crocacin C.1

Scheme 11

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Materials

     

References

  1. Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2008, 130, 14084.

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