Synthesis and resolution of R(−)-5-hexyn-3-ol

Abstract

. J . Chem. 63, 65 1 (1 985).The resolution of (*)-5-hexyn-3-01 (1) was effected by high performance chromatography of its 0-methyl mandelic esters 3 and 4. The absolute configuration of (-) and (+)-5-hexyn-3-01 were determined by comparison with an authentic sample prepared from D(+)-glucose. BERNARD L. ROY et PIERRE DESLONGCHAMPS. Can. J . Chem. 63, 651 (1985). La rCsolution du (?)-hexyne-5 01-3 (1) fut rtalisCe grice ii la chromatographie ii haute performance de ses esters 0-methyl mandtlique 3 et 4. La configuration absolue du (-) et (+)-hexyne-5 01-3 fut determinee par comparaison avec un echantillon prepare ii partir du D ( + ) -~~u c o s~.As part of our work on the total synthesis of erythromycin A,' the R enantiorner of 5-hexyn-3-01 ( 1 R ) was required as starting material. We have obtained this compound by resolution and wish to report this work.The racemic form of 1 (Scheme I), which is readily available from the condensation of propargyl magnesium bromide on propionaldehyde (3), was transformed into the corresponding diasteroisomeric 0-methyl mandelic esters 3 and 4 by reaction with optically active acid chloride 2 (4). The separation of diastereoisomers 3 and 4 was carried out by high performance chromatography using toluene -ethyl acetate (99.5 : 0.5) as the solvent. After separation, the more polar compound had an [a]: +86" ( c I . I, CHCI,) and the less polar had an [a]: +2S0 (C 1.9, CHCI,).Referring to Mosher's work (4) on the anisotropic effect of the phenyl ring on proton chemical shifts, we were able to predict that the more polar diastereoisomer would correspond to 3 and the less polar to 4, having respectively the SR and the SS absolute configuration. This assignment is based on the fact that (a) the protons at CI and C2 in 3 (Table I ) absorb at a higher field than those in 4, and (b) the protons at C4 and C6 in 3 absorb at a lower field than those in 4.Hydrolysis of the more polar diastereoisomer 3 gave an alcohol ([a]: -4O (c 1. I, CHCI,)) which must therefore have the R absolute configuration, whereas the less polar diastereoisomer 4 yielded an alcohol ([a]: +4" ( c 2.1, CHCI,)) having the S configuration.This configurational assignment based on Mosher's work (4), was rigorously established by preparing a sample of alcohol 1R starting from D-glucose using the method described in Scheme 2. The known compound 5 (5,6) was prepared in four steps from D-glucose. The alcohol 1R obtained from compound 11 was levorotatory ([a];?: -4" (c I. I, CHCI,)), so our original assignment was correct. The alcohol 1 s can also be transformed into the benzoate 12 of alcohol 1R using the Mitsunobu inversion procedure (7). The benzoate 12 obtained had a rotation ([a]: +2S0 ( c 1.6, CHCI,)) essentially identical to that of an authentic sample of 12 ([af +29" (c 1.2, CHCI,)) prepared by benzoylation of alcohol I R . ExperimentalThe infrared (ir) spectra were taken on a Perkin-Elmer 681 spec- 'NSERCC and FCAC predoctoral fellowships, 1980-1984 trophotometer. Proton nmr spectra were recorded on a Bruker WP-60 o...

Substrate-Dependent Stereochemical Course of the (Z)-13-Desaturation Catalyzed by the Processionary Moth Multifunctional Desaturase

“…These compounds were synthesized in our laboratory by the same methodology . Likewise, optical rotation signs of homopropargylic 5-hexyn-3-ol stereoisomers agreed with previously reported data . Number and location of the deuterium tags and labels were as expected as concluded from the 1 H and 13 C NMR analyses.…”

“…18 Likewise, optical rotation signs of homopropargylic 5-hexyn-3-ol stereoisomers agreed with previously reported data. 25 Number and location of the deuterium tags and labels were as expected as concluded from the 1 H and 13 C NMR analyses. The final deuterium contents of the acids 1 were determined by GC-MS (EI) analysis of their respective methyl esters and under the optimum synthetic conditions, mean ratios of…”

Novel Chemoenzymatic Strategy for the Synthesis of Enantiomerically Pure Secondary Alcohols with Sterically Similar Substituents

“…The procedure described in this paper appears to be an advantageous alternative when compared to other chemical methods of production of enantiomerically pure secondary alcohols such as reduction of alkynones by chiral borane reagents . Likewise, we think that the present enzymatic approach could be easily extrapolated to the preparation of chiral homopropargyl alcohols that have been used as precursors of chiral fluorinated syn-thons in mechanistic studies of fatty acid biomodification …”

An example of spontaneous resolution by sublimation

“…Significantly, the nonsublimed solid in each instance exhibited no meaningful optical rotation.7® In order to define absolute configurational assignments to the enantiomers of 2, the racemic alcohol was condensed with the acyl chloride of (S)-(+)-0-methylmandelic acid. 8 The absolute configurations of the diastereomers 3, [alo20 +34.4°( c 2.58, C2H5OH), and 4, [a]D20 +21.5°( c 3.03, C2H5OH), whose complete separation was achieved by MPLC on silica gel, were deduced in the following manner. As the Mosher9 and Trost10 NMR correlations would suggest, the downfield position of H-6ei0 in 3 ( 1.79) relative to 4 ( 1.15) implicates the latter as experiencing an upfield shift because of long-range eclipsing by the phenyl ring.…”