869218-54-2Relevant academic research and scientific papers
Preparation of chiral α-oxy-[2H1]methyllithiums of 99% ee and determination of their configurational stability
Kapeller, Dagmar,Barth, Roland,Mereiter, Kurt,Hammerschmidt, Friedrich
, p. 914 - 923 (2007/10/03)
(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 H2O 2 to give (S)- and (R)-tributylstannyl-[1-2H 2]methanol of 99% ee, respectively. Treatment of their respective phosphates with n-BuLi at -78 and 0 °C gave microscopically configurationally stable phosphinyloxy-substituted [2H 1]methyllithiums, which rearranged to hydroxy-[1-2H 1]-methylphosphonates of ee > 98% (phosphate-phosphonate rearrangement). The N,N-iisopropylcarbamates 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them were deduced from a single-crystal X-ray structure analysis of a carbamate in which the tributylstannyl group had been replaced by the [(1R)-menthyl]dimethylstannyl group.
Direct chemical synthesis of chiral methanol of 98% ee and its conversion to [2H1,3H]methyl tosylate and [ 2H1,3H-methyl]methionine
Simov, Biljana Peric,Wuggenig, Frank,Mereiter, Kurt,Andres, Hendrik,France, Julien,Schnelli, Peter,Hammerschmidt, Friedrich
, p. 13934 - 13940 (2007/10/03)
This paper describes the synthesis of chiral methanols [(R)- and (S)-CHDTOH] in a total of 12 steps starting from (chloromethyl) dimethylphenylsilane. The metalated carbamates derived from (dimethylphenylsilyl)methanol and secondary amines were borylated at low temperatures (-78 or -94°C) using borates derived from fert-butyl alcohol and (+)-pinane-2,3-diol or (R,R)-1,2-dicyclohexylethane-1,2-diol to give diastereomeric boronates (dr 1:1 to 5:1). The carbamoyloxy group could be replaced smoothly with inversion of configuration by an isotope of hydrogen using LiAIH(D)4 [or LiBEt3H(D,T)]. If the individual diastereomeric boronates were reduced with LiAID4 and oxidized with H2O2/NaHCO3, monodeuterated (dimethylphenylsilyl)methanols of ee > 98% resulted. The absolute configurations of the boronates were based on a single-crystal X-ray structure analysis. Brook rearrangement of the enantiomers of (dimethylphenylsilyl)-[ 2H1,3H]methanol prepared similarly furnished the chiral methanols which were isolated as 3,5-dinitrobenzoates in 81% and 90% yield, respectively. For determination of the enantiomeric excesses (98%), the methyl groups were transferred to the nitrogen of (S)-2-methylpiperidine and 3H{1H} NMR spectra were recorded. The Brook rearrangement is a stereospecific process following a retentive course. The chiral methanols were also transformed into methyl tosylates used to prepare [2H 1,3H-methyl]methionines in high overall yields (>80%).
