869218-56-4Relevant academic research and scientific papers
Formal and improved synthesis of enantiopure chiral methanol
Schweifer, Anna,Hammerschmidt, Friedrich
, p. 7605 - 7610 (2008/12/20)
[D2]Methanol was converted to the carbamate derived from 2,2,6,6-tetramethylpiperidine. It was metalated with s-BuLi/TMEDA at -78 °C with a high primary kinetic isotope effect to give an α-oxymethyllithium, which was silylated with chlorodimethylphenylsilane. The silylmethyl carbamate formed was lithiated and borylated with the borate derived from tert-butanol and (R,R)-1,2-dicyclohexylethane-1,2-diol to give diastereomeric boronates, which were separated by preparative HPLC and can in principle be converted to enantiopure chiral methanols. Thus, both enantiomers are easily accessible in nine linear steps.
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%).
