Synthesis of Enantioenriched Tertiary Boronic Esters by the Lithiation/Borylation of Secondary Alkyl Benzoates

Alexander P. Pulis, Daniel J. Blair, Eva Torres, Varinder K. Aggarwal*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

53 Citations (Scopus)

Abstract

Simple, secondary 2,4,6-triisopropyl benzoates (TIB esters) and secondary dialkyl N,N-diisopropyl carbamates have been reported to be resistant to deprotonation by strong bases. We have found that the combination of sBuLi (1.6 equiv) and TMEDA (6 equiv) in CPME at -60 degrees C enables deprotonation of unactivated secondary dialkyl TIB esters, but not the carbamates. These carbanions were reacted with a range of neopentyl boronic esters which, after 1,2-metalate rearrangement and oxidation, gave a range of tertiary alcohols in high yield and universally high er. Further functional group transformations of the tertiary boronic esters were demonstrated (conversion to quaternary centers, C-tertiary amines) together with application of the methodology to the synthesis of the simplest unbranched hydrocarbon bearing a quaternary center, (R)-4-ethyl-4-methyloctane, validating the synthetic utility of the methodology.

Original languageEnglish
Pages (from-to)16054-16057
Number of pages4
JournalJournal of the American Chemical Society
Volume135
Issue number43
DOIs
Publication statusPublished - 30 Oct 2013

Keywords

  • LITHIATION-SUBSTITUTION SEQUENCES
  • QUATERNARY STEREOGENIC CENTERS
  • ENANTIOSELECTIVE SYNTHESIS
  • ASYMMETRIC-SYNTHESIS
  • PRACTICAL SYNTHESIS
  • CONJUGATE BORATION
  • KETONES
  • ALCOHOLS
  • REAGENTS
  • BORYLATION

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