- The Hendrickson reagent and the Mitsunobu reaction: A mechanistic study
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The alkoxytriphenylphosphonium ion intermediate of the Mitsunobu reaction can be generated using the Hendrickson reagent, triphenylphosphonium anhydride trifluoromethanesulfonate, 1. Strangely, while the reagent 1 can be used in place of the Mitsunobu reagents (triphenylphosphine and a dialkylazodicarboxylate) for the esterification of primary alcohols, secondary alcohols such as menthol undergo elimination. Evidence is presented to show that this unexpected result is due to the presence of trialkylammonium triflate salts. Such salts lead to a dramatic decrease in the rate of esterification relative to competing elimination. The Mitsunobu esterification of menthol with p-nitrobenzoic acid was re-examined and the occurrence of elimination reported for the first time. The presence of traces of tetrabutylammonium triflate led to a dramatic reduction in the yield of inverted ester and a corresponding increase in the yield of anti elimination product 2-menthene. The mechanism of the Mitsunobu reaction is discussed in the light of the dramatic salt effect on both the rate and outcome of the reaction and the possible involvement of ion pair clustering. In contrast, use of the reagent 1 resulted in syn elimination to give a 1:2 mixture of 2- and 3-menthenes. Finally, 1 and sodium azide can be used to convert a primary alcohol into an azide in high yield. There was no reaction under Mitsunobu conditions.
- Elson, Kathryn E.,Jenkins, Ian D.,Loughlin, Wendy A.
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- Chirality transfer through sulfur or selenium to chiral propellers
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The mechanism of chirality transfer from a chiral alkyl substituent to a trityl moiety through sulfur or selenium atoms is analysed and discussed on the basis of ECD measurements, DFT structure and ECD spectra calculations. It is shown that the presence o
- Skowronek, Pawel,cianowski, Jacek,Pacula, Agata J.,Gawroski, Jacek
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- Structure-Odor Activity Studies on Monoterpenoid Mercaptans Synthesized by Changing the Structural Motifs of the Key Food Odorant 1-p-Menthene-8-thiol
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1-p-Menthene-8-thiol (1) has been discovered as the key odorant in grapefruit juice several decades ago and contributes to the overall odor of the fruit with an extremely low odor threshold of 0.000034 ng/L in air. This value is among the lowest odor thresholds ever reported for a food odorant. To check whether modifications in the structure of 1 would lead to changes in odor threshold and odor quality, 34 mercapto-containing p-menthane and 1-p-menthene derivatives as well as several aromatic and open-chain mercapto monoterpenoids were synthesized. Eighteen of them are reported for the first time in the literature, and their odor thresholds and odor qualities as well as analytical data are supplied. A comparison of the sensory data with those of 1 showed that hydrogenation of the double bond led to a clear increase in the odor threshold. Furthermore, moving the mercapto group into the ring always resulted in higher odor thresholds compared to thiols with a mercapto group in the side chains. Although all tertiary thiols always exhibited low odor thresholds, none of the 31 compounds reached the extremely low threshold of 1. Also, none of the synthesized mercapto monoterpenoids showed a similar odor quality resembling grapefruit. Although the saturated and aromatic analogues exhibited similar scents as 1, the aromas of the majority of the other compounds were described as sulfury, rubber-like, burned, soapy, or even mushroom-like. NMR and MS data as well as retention indices of the 23 newly reported sulfur-containing compounds might aid in future research to identify terpene-derived mercaptans possibly present in trace levels in foods.
- Schoenauer, Sebastian,Schieberle, Peter
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p. 3849 - 3861
(2016/06/01)
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- Synthesis of (Racemization Prone) Optically Active Thiols by SN2 Substitution Using Cesium Thiocarboxylates
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The cesium salt of thioacetic acid is prepared by treatment with cesium carbonate.This salt has a solubility of about 0.7 M in DMF (even higher in Me2SO) at 50 deg C.The mesylates of (R)-2-octanol, the ethyl ester and N,N-dimethyl amide of (R)-mandelic acid, (S)-ethyl lactate, (S)-methyl 3-phenyllactate, and (S)-diethyl malate underwent clean SN2 substitution in DMF solution.Racemization occured only in the case of the mesylate of ethyl mandelate when allowed to react in DMF, but complete inversion was achieved on use of absolute ethanol as solvent.Hydrolysis or aminolysis is used to deacylate the thiols (except for aliphatic thioacetates, which are deprotected by treatment with lithium aluminum hydride) to afford 2-mercapto esters or amides.Owing to the sensitivity of mercapto-bearing carbon, some racemization (0-20percent depending on the system) occurs during deprotection.An alternate route to the same materials prepared by the cesium thiocarboxylate method involves treatment of the free alcohol with thioacetic acid in the presence of twofold amount of the preformed salt from diisopropyl azodicarboxylate (DIAD) and triphenylphosphine.This method works well except for ethyl mandelate and N,N-dimethylmandelamide.Scale-up of the reaction is difficult, however, owing to the need for a chromatographic separation.Various NMR methods for determining the enantiomeric excesses of the various products are described.Particularly useful for determination of the high enantiomeric excesses is an internal calibration method based on the use of 13C satellite peaks in the presence of a chiral shift reagent.The enantiomeric excesses of the thiols were determined by conversion to the phosphonodithioates followed by measurement of the meso/d,l ratios obtained from 31P NMR spectra.Attempts to hydrolyze 2-acetylthio esters to the free 2-mercapto carboxylic acids lead to 10-40percent racemization depending on the compound.A partial solution to this problem was found by use of optically pure S bromides obtained from diazotation of (S)-alanine, (S)-phenylalanine, and (S)-valine in the presence of bromide.These bromides, on treatment with cesium thiobenzoate, underwent clean SN2 substitution, and debenzoylation could be brought about without significant racemization
- Strijtveen, Bert,Kellogg, Richard M.
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p. 3664 - 3671
(2007/10/02)
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