Attention:

Certain features of Sigma-Aldrich.com will be down for maintenance the evening of Friday August 18th starting at 8:00 pm CDT until Saturday August 19th at 12:01 pm CDT.   Please note that you still have telephone and email access to our local offices. We apologize for any inconvenience.

Synthesis of Polyene Natural Products Using Polyene MIDA Boronates

By: Josephine Nakhla, ChemFiles Volume 9 Article 1

Palladium-catalyzed cross-coupling reactions are ideal methods for the synthesis of polyenes because of the stereospecificity of the reactions and the mildness of the reaction conditions. However, polyenylboronic acids are very unstable and therefore difficult to employ in the synthesis of polyenes via Suzuki reactions. In another exemplary demonstration of the MIDA boronates’ stability and efficiency in iterative cross-coupling, Burke and coworkers utilized a common alkenyl MIDA boronate (703478) to create a series of polyenyl building blocks. The MIDA boronate terminus is inert to Heck, Stille, and Suzuki couplings, yielding butadienyl MIDA boronates (Scheme 4).

Scheme 4 (703478)

The alkenyl MIDA boronate (703478) was also applied to the synthesis of the carotenoid all-trans-retinal. Demonstrating the feasibility of polyenyl MIDA boronates in synthesis, boron deprotection of the intermediate 4 proceeded smoothly to generate the boronic acid, which was subsequently coupled with the β-bromo enal to provide all-trans-retinal (Scheme 5).

Scheme 5 (703478)

Miyaura borylation (Scheme 6, to provide 6) and Sonogashira and Negishi couplings (to provide 5 and 7, respectively) that yield bis-metalated lynchpin-type reagents were also demonstrated. Synthetic reagent 6 was further elaborated in the polyene natural product synthesis of β-parinaric acid (Scheme 7) and reagent 7 was employed in the preparation of the polyene chain of amphotericin B (Scheme 8).1

Scheme 6 (703478)

Scheme 7

Scheme 8 (703478)

back to top Back to Top

Materials

     

References

  1. Lee, S. J.; Gray, K. C.; Paek, J. S.; Burke, M.D. J. Am. Chem. Soc. 2008, 130, 466.

back to top Back to Top

Related Links