Preparing Terminal Alkynes: Vinyl N,N-Diisopropylcarbamate for Stereospecific Alkynylation of Chiral Boronic Esters

Introduction

Enantioenriched chiral alkyl boronic esters are highly useful reagents that can be easily prepared and subsequently transformed into a variety of functional groups.1 To add to the arsenal of transformations boronic esters can undergo, Professor Varinder Aggarwal and co-workers developed a stereospecific alkynylation of chiral secondary and tertiary pinacol boronic esters, allowing the facile preparation of terminal alkynes bearing α‑chiral centers.2 Prior to this report, the alkynylation of boronic esters was only possible in a racemic fashion.3 Professor Aggarwal’s approach uses vinyl N,N-diisopropyl carbamate (900510) in Zweifel olefinations with chiral alkylboronic esters to afford intermediate vinyl carbamates that subsequently undergo facile base-mediated elimination to provide the terminal alkyne products with complete enantiospecificity.

Vinyl N,N-Diisopropyl Carbamate

 

Representative Applications

1. Vinyl N,N-diisopropylcarbamate has been used in stereospecific alkynylations of hindered secondary and tertiary alkylboronic esters.2

Advantages

  • Bench-stable reagent
  • Allows the stereospecific alkynylation of chiral pinacol boronic esters2
  • Suitable for reaction with hindered secondary and tertiary boronic esters2

Vinyl N,N-Diisopropylcarbamate


2. Deprotonation of vinyl N,N-diisopropylcarbamate with sBuLi (195596) provides a vinyl lithium intermediate that has been used in asymmetric syntheses of annulated cyclopentenones4 and in the preparation of other synthetically useful products via sulfonylation5 and iodination reactions.6

 

Deprotonation of vinyl N,N-Diisopropylcarbamate

Thank you to Adam Noble and Varinder Aggarwal for contributing this Technology Spotlight!
 

Materials

     

References

  1. Hall, D. G.; Lee, J. C. H.; Ding, J. Pure Appl. Chem. 2012, 84, 2263.
  2. Wang, Y.; Noble, A.; Myers, E. L.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2016, 55, 4270.
  3. Huang, H.; Zhang, G.; Gong, L.; Zhang, S.; Chen, Y. J. Am. Chem. Soc. 2014, 136, 2280.
  4. Siemer, M.; Fröhlich, R.; Hoppe, D. Synthesis 2008, 2264­.
  5. Chen, Y.-L.; Hoppe, D. J. Org. Chem. 2009, 74, 4188.
  6. Tomida, Y.; Nagaki, A.; Yoshida, J. J. Am. Chem. Soc. 2011, 133, 3744.