Preparation of Chiral α-Oxy-[2H1]methyllithiums of 99% ee and Determination of Their Configurational Stability

• Published in: Journal of the American Chemical Society Vol. 129; no. 4; pp. 914 - 923
• Main Authors: Kapeller, Dagmar, Barth, Roland, Mereiter, Kurt, Hammerschmidt, Friedrich
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 31.01.2007; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; TRANSFORMATION; REARRANGEMENT; DEPROTONATION; ENANTIOSELECTIVE SYNTHESIS; ORGANOMETALLIC REAGENTS; STABLE CARBANIONS; STEREOCHEMISTRY; SUBSTITUTED ORGANOLITHIUM COMPOUNDS; CARBENOID NATURE; CYCLOPROPANES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja066183s

(Tributylstannyl)methyl 2,2,6,6-tetramethylpiperidine-1-carboxylate was metalated with t-BuLi/TMEDA at −78 °C and borylated with the mixed borate derived from (R,R)-1,2-dicyclohexylethane-1,2-diol and t-butanol to give diastereomeric boronates 31/32 in equal amounts. Boronates 31 and 32 were reduced with LiBEt3D and then oxidized with basic H2O2 to give (S)- and (R)-tributylstannyl-[1-2H1]methanol of 99% ee, respectively. Treatment of their respective phosphates with n-BuLi at −78 and 0 °C gave microscopically configurationally stable phosphinyloxy-substituted [2H1]methyllithiums, which rearranged to hydroxy-[1-2H1]methylphosphonates of ee > 98% (phosphate−phosphonate rearrangement). The N,N-diisopropylcarbamates of the enantiomeric tributylstannyl-[1-2H1]methanols were transmetalated to give carbamoyloxy-substituted chiral [2H1]methyllithiums, which were macroscopically configurationally stable for prolonged periods of time (up to 3 h, ee still 99%) at −78 °C, deduced from trapping experiments with benzaldehyde. The chemical stability of these methyllithiums ended at −50 °C. The stereochemistry of the monoprotected and monodeuterated 1-phenylethane-1,2-diols obtained was secured by spectroscopic comparison of their Mosher esters with that of all four stereoisomeric 1-phenyl-[1-2H1]ethane-1,2-diols synthesized independently. Furthermore, the configurations of the boronates and the chiral methyllithiums derived from them were deduced from a single-crystal X-ray structure analysis of a carbamate in which the tributylstannyl group had been replaced by the [(1R)-menthyl]dimethylstannyl group.