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

• Published in: Journal of the American Chemical Society Vol. 135; no. 43; pp. 16054 - 16057
• Main Authors: Pulis, Alexander P, Blair, Daniel J, Torres, Eva, Aggarwal, Varinder K
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 30.10.2013; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; ALCOHOLS; KETONES; ASYMMETRIC-SYNTHESIS; PRACTICAL SYNTHESIS; HYDROGENATION; ENANTIOSELECTIVE SYNTHESIS; CONVERSION; CONJUGATE BORATION; BORYLATION; LITHIATION-SUBSTITUTION SEQUENCES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja409100y

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 °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.