Chemo‐Enzymatic Synthesis of All Isomers of 2‐Methylbutane‐1,2,3,4‐tetraol – Important Contributors to Atmospheric Aerosols

Abstract

By a combination of stereospecific osmium catalyzed oxidation of dimethyl citraconate and lipase catalysed enantioselective resolution of the formed dimethyl (2R*,3S*)‐2,3‐dihydroxy‐2‐methylbutanedioate, followed by reduction, (2R,3S)‐ and (2S,3R)‐2‐methylbutane‐1,2,3,4‐tetraol were isolated. Similar reactions starting with dimethyl mesaconate gave the isomers, (2R,3R)‐ and (2S,3S)‐2‐methylbutane‐1,2,3,4‐tetraol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Physical state of 2-methylbutane-1,2,3,4-tetraol in pure and internally mixed aerosols

“…For our study, we needed 2-methylbutane-1,2,3,4-tetraol (tetraol) in gram amounts as racemates and as enantiomerically enriched materials of all of its four stereoisomers. Because of their importance in biological and atmospheric research the syntheses of the stereoisomers of tetraol have been devised already (Cole-Filipiak et al, 2010;Duvold et al, 1997;Ebben et 20 al., 2014;Enders et al, 2007;Fontana et al, 2000;Ghosh et al, 2012;Giner et al, 2002;Hoeffler et al, 2000;Koumbis et al, 2007;Moen et al, 2007;Robinson et al, 2009;Sharma et al, 2008;Urbansky et al, 2004). Among the reported syntheses, the reports of Ghosh et al (Ghosh et al, 2012), Moen et al, (Moen et al, 2007) and Sharma et al (Sharma et al, 2008) appeared most attractive to us as they show an access to both diastereomers through the same reaction sequence and give the four stereoisomers as stereochemically highly homogeneous materials with enantiomeric excesses (ee) of 80-99%.…”

“…Among the reported syntheses, the reports of Ghosh et al (Ghosh et al, 2012), Moen et al, (Moen et al, 2007) and Sharma et al (Sharma et al, 2008) appeared most attractive to us as they show an access to both diastereomers through the same reaction sequence and give the four stereoisomers as stereochemically highly homogeneous materials with enantiomeric excesses (ee) of 80-99%. We decided 25 to use the strategy of Moen et al (Moen et al, 2007) because it requires the least number of steps. It takes up the procedures described by Anthonsen et al (Anthonsen et al, 1976(Anthonsen et al, , 1980 for the preparation of the two diastereomeric tetraols as racemates.…”

“…CAL-A catalyses the esterification of the secondary hydroxyl groups of diols 3 with vinyl butanoate and thereby favours the diols (2R,3S)-3 and (2S,3S)-3 as reaction partners over their enantiomers (Moen et al, 2007). The attempt of a chiral resolution of rac-(2R,3R)-diol 3 according to the conditions 20 described by Moen et al (Moen et al, 2007), however on a scale of 3 g instead of 1 g of diol and with CAL-A immobilized on Immobead 150 instead of Novozym 735, failed. No reaction occurred within 3 days.…”

“…The reported work-up had to be modified for running this reaction on a multigram scale, such as starting with 38 g 5 of diester (E)-2 and 107 g of diester (Z)-2. Moen et al described the removal of tert-butanol by distillation followed by an extraction of the residual aqueous phase with diethyl ether (Moen et al, 2007). Applying this procedure to isolate diol rac-(2R,3S)-3 on a multigram scale, we found this procedure to be impractical because several litres of diethyl ether would be needed for extraction of this diol due to its low solubility.…”

“…Following the report of Moen et al, (Moen et al, 2007) syn-dihydroxylations of the diesters (E)-and (Z)-2 were achieved through applying K 2 OsO 2 (OH) 4 and N-methylmorpholine-N-oxide with the addition of citric acid in a mixture of tert-butanol and water. The reported work-up had to be modified for running this reaction on a multigram scale, such as starting with 38 g 5 of diester (E)-2 and 107 g of diester (Z)-2.…”