Technology Spotlight

Yudin and Coworkers Develop a New Line of MIDA Boronate Esters: Amphoteric Alpha-Boryl Aldehydes

MIDA boronates, first developed by Burke and coworkers,1 have been shown to be effective in iterative cross-coupling sequences to provide access to myriad biaryl small molecules and complex natural products.1-2 A serendipitous discovery was made in the Andrei Yudin group.3 In the course of investigating MIDA boronates in selective epoxide openings, α-MIDA-boryl aldehydes were discovered providing an exciting new functional handle not reported in this field. These versatile α-MIDA-boryl aldehydes are now available through Aldrich Chemistry as bench-top stable, white solids.

 

New and Versatile Functional Handle

 

Amphoteric molecules contain a counterintuitive combination of reaction centers with opposing reactvitiy.  The amphoteric nature of this new product line presents a scaffold for high chemselectivity in a variety of chemical transformations. Several potentially useful building blocks can be accessed in one step from our portfolio of α-MIDA-boryl aldehydes ranging from vinyl triflates for subsequent cross-coupling reactions to carboxylic acids for nucleophlic couplings.

 

Diversity with High Chemoselectivity

 

The MIDA ester also acts as a directing group for diastereoselective Barbier-type additions. The concomitant allylic alcohol can also be further transformed into valuable building blocks. Syn-1,2-diols and skipped dienes are obtainable under oxidative and basic conditions from the allylic alcohol building block.

 

Highly Diastereoselectivite Transormations

 

A three component coupling from the enamide and TIPS-vinyl ethers provided a series of novel unnatural amino acids from the corresponding boronic acid pinacol esters (obtained from converting the MIDA ester with pinacol). These pinacol esters underwent Petasis boro-Mannich additions to in situ formed imines (an amine and glyoxylic acid) to provide several unnatural amino acids. This application not only expands the scope of this product line, but also expands the scope of all of our current MIDA boronates offered in our portfolio.


MIDA boronates portfolio



Materials List

 

Product No. Description Molecular Formula Cart No.
MIDA070 Isobutyl-alpha-MIDA-boryl aldehyde AldrichCPR C11H18BNO5
MIDA075 4-Fluorophenyl-alpha-MIDA-boryl aldehyde AldrichCPR C13H13BFNO5
MIDA072 Phenyl-alpha-MIDA-boryl aldehyde AldrichCPR C13H14BNO5
MIDA071 Cyclohexyl-alpha-MIDA-boryl aldehyde AldrichCPR C13H20BNO5
MIDA074 4-Tolyl-alpha-MIDA-boryl aldehyde AldrichCPR C14H16BNO5
MIDA073 Benzyl-alpha-MIDA-boryl aldehyde AldrichCPR C14H16BNO5
MIDA076 1,1′-Biphenyl-alpha-MIDA-boryl aldehyde AldrichCPR C19H18BNO5

 

References

  1. Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716-6717.
  2. (a) Lee, S. J.; Gray, K. C.; Paek, J. S.; Burke, M. S.; J. Am. Chem. Soc. 2008, 130, 466-468. (b) Gillis, E. P., Burke, M. D. J. Am. Chem. Soc. 2008, 130, 14084-14085. (c) Uno, B. E.; Gillis, E. P.; Burke, M. D. Tetrahedron 2009, 65, 3130-3138. (d) Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2009, 131, 6961-6963. (e) Gillis, E. P.; Burke, M. D. Aldrichimica Acta 2009, 42, 17-27. (f) Ballmer, S. G.; Gillis, E. P.; Burke, M. D. Org. Synth. 2009, 86, 344-359. (g) Struble, J. R.; Lee, S. J.; Burke, M. D. Tetrahedron 2010, 66, 4710-4718. (h) Dick, G. R.; Knapp, E. P.; Burke, M. D. Org. Lett. 2010, 12, 2314-2317. (i) Woerly, E. M.; Cherney, A. H.; Davis, E. K.; Burke, M. D. J. Am. Chem. Soc. 2010, 132, 6941-6943. (j) Lee, S. J.; Anderson, T. M.; Burke, M. D. Angew. Chem. Int. Ed. 2010, 49, 8860-8863. (k) Woerly, E. M.; Struble, J. R.; Palyam, N.; O’Hara, S. P.; Burke, M. D. Tetrahedron 2011, 67, 4333-4343. (l) Fujii, S.; Chang, S. Y.; Burke, M. D. Angew. Chem. Int. Ed. 2011, 50, 7862-7864. (m) Li, J.; Burke, M. D. J. Am. Chem. Soc. 2011, 133, 13774-13777. (n) Dick, G. R.; Woerly, E. M.; Burke, M. D. Angew. Chem. Int. Ed. 2012, 51, 2667-2672.
  3. He, Z.; Yudin, A. K. J. Am. Chem. Soc. 2011, 133, 13770-13773.