Synthesis of (S,S)‐Diisopropyl Tartrate (E)‐Crotylboronate and Its Reaction with Aldehydes: (2R,3R,4R)‐1,2‐Dideoxy‐2‐Ethenyl‐4,5‐O‐(1‐Methylethylidene)‐Xylitol

Abstract

Procedure A. (S,S)-Diisopropyl tartrate (E)-crotylboronate 2An oven-dried 500-mL, three-necked, round-bottomed flask equipped with a 5-cm, eggshaped stir bar, a rubber septum, and a digital and traceable thermocouple (Note 1) is connected to an argon line and is charged with t-BuOK (20.0 g, 95% purity, 170 mmol, 1.0 equiv) (Note 2) and anhydrous THF (85 mL) (Note 3) added by a syringe. This mixture is cooled to −78 ºC with a dry ice/acetone bath, and then trans-2-butene (19.2 mL, 204 mmol, 1.2 equiv) (Note 4), condensed from a gas lecture cylinder into a 25-mL graduated cylinder immersed in a dry ice/acetone bath, is added via cannula. n-BuLi (2.5 M in hexane, 68.0 mL, 170.0 mmol) (Note 5) is added dropwise over 50 min using a syringe pump to make sure that the internal temperature does not rise above −65 ºC. After the addition is complete, the cooling bath is removed, and the resultant yellow mixture is allowed to warm until the internal temperature reaches −50 ºC (about 5 min). Then the reaction flask is quickly moved to an acetone bath precooled with dry ice to −50 ºC. The internal temperature of the reaction solution is maintained between −50.0 ºC to −50.5 ºC for 25 min (Note 6) and then immediately recooled to −78 ºC by moving the reaction flask to a dry ice/acetone bath.1 The digital and traceable thermocouple (Fisherbrand, −200 ºC ~ +1370 ºC) was purchased from Fisher Scientific Company. 2 Potassium tert-butoxide (95% purity) was purchased from Sigma-Aldrich chemical Company, Inc., and stored and transferred in a glove box. 3 Tetrahydrofuran was purchased from Fisher Chemical Company and dried by fresh distillation from sodium/benzophenone ketyl under an atmosphere of dry argon. 4 The checkers purchased trans-2-butene from TCI (min. 99.0%, GC). The submitters purchased trans-2-butene (99+% purity) from Aldrich Chemical Company, Inc. and used as stored. It is necessary to use 1.1-1.2 equiv of trans-2-butene in order to compensate for the loss of the material during transfer. 5 n-Butyllithium (2.5 M in hexane) was purchased from Aldrich Chemical Company, Inc., stored at 5 ºC and used as received. 6 The temperature of the central part of the reaction solution was monitored. Placing the probe of the thermocouple against reaction flask wall resulted in the isomeric purity of the crotylboronate reagent being reduced by 1-2%. The internal temperature of the solution was maintained between −55 ºC and −50 ºC by removing the flask from the cooling bath (dry ice/acetone) and allowing it to approach −50 ºC, at which time the flask was resubmerged to lower the temperature. No deterioration of selectivity was observed. NIH Public Access Author ManuscriptOrganic Synth. Author manuscript; available in PMC 2011 June 9.Published in final edited form as:Organic Synth. 2011 ; 88: 181-196. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTriisopropylborate (39.9 mL, 98% purity, 170 mmol) (Note 7) is added dropwise over 50 min via a syringe pump to the above orange solution of (E)-crotylpotassium 1 to m...