80041-01-6

Usage

Uses

Used in Beverage Industry:
(E)-Whiskeylactone, 5-butyldihydro-4-methyl-2(3H)-furanone, and (+)-trans-Whiskeylactone are used as key components in the production of whiskey. They contribute to the unique flavor and aroma profile of the spirit, making them essential for creating the desired taste and sensory experience.
1. (E)-Whiskeylactone is used as a flavor compound for its sweet, coconut-like aroma, which adds a pleasant and distinctive note to the whiskey.
2. 5-butyldihydro-4-methyl-2(3H)-furanone is used as a flavor compound for its fruity, caramel notes, which contribute to the whiskey's rich and complex taste.
3. (+)-trans-Whiskeylactone is used as a flavor compound for its ability to enhance the warm, woody character of the whiskey, adding depth and complexity to the overall aroma.

Upstream product

• 693-03-8 n-butyl magnesium bromide 
• 65038-34-8 3-formyl-butyric acid methyl ester 
• 87434-05-7 erithro-3-methyl-1,4-octandiol 
• 93828-06-9 (4R,5S)-5-Butyl-4-methyl-tetrahydro-furan-2-ol 
• 102587-17-7 threo-2-(2-methyl-3-hydroxyheptylidene)-1,3-dithiane 
• 31705-09-6 (2α,3β)-(+/-)-2-Butyltetrahydro-3-methylfuran 
• 127459-10-3 (4R,5R)-5-Butyl-4-methyl-3-phenylsulfanyl-dihydro-furan-2-one 
• 87433-77-0 ((1S,2R)-2-Butyl-cyclopropyl)-acetic acid methyl ester 
• 126188-65-6 4-methyl-5-(n-butyl)-2(5H)-furanone 
• 59086-42-9 3-methyl-4-oxo-octanoic acid 
• 4938-52-7 1-hepten-3-ol 
• 87143-54-2 C₁₀H₂₀O₂ 
• 109-72-8 n-butyllithium 
• 24406-16-4 lithium di-n-butylcuprate 

Downstream Products

• 105119-22-0 (4R,5S)-trans-5-n-butyl-4-methyl-4,5-dihydro-2(3H)-furanone 
• 104910-77-2 i‐propyl‐4‐hydroxy‐3‐methyloctanoate 
• 741717-02-2 (3S,4R)-1-t-butyldiphenylsilyloxy-3-methyl-4-O-(2',3',4',6'-tetra-O-pivaloyl-β-D-glucopyranosyl)octane 
• 741717-01-1 (3R,4S)-1-t-butyldiphenylsilyloxy-3-methyl-4-O-(2',3',4',6'-tetra-O-pivaloyl-β-D-glucopyranosyl)octane 
• 80041-00-5 (4S,5S)-5-n-butyl-4-methyl-4,5-dihydro-2(3H)-furanone 
• 105015-53-0 (4R,5R)-5-n-butyl-4-methyl-4,5-dihydro-2(3H)-furanone 
• 104910-75-0 i‐propyl‐4‐hydroxy‐3‐methyloctanoate 
• 87434-05-7 erithro-3-methyl-1,4-octandiol 
• 741716-99-4 (3R,4R)-3-methyl-4-O-β-D-glucopyranosyloctanoic acid 
• 173355-98-1 (3S,4S)-3-methyl-4-O-β-D-glucopyranosyloctanoic acid 
• 741716-98-3 (3R,4R)-benzyl 3-methyl-4-O-(2',3',4',6'-tetra-O-pivaloyl-β-D-glucopyranosyl)octanoate 
• 741716-97-2 (3S,4S)-benzyl 3-methyl-4-O-(2',3',4',6'-tetra-O-pivaloyl-β-D-glucopyranosyl)octanoate 

Relevant academic research and scientific papers

Exploiting the vicinal disubstituent effect on the diastereoselective synthesis of γ and δ lactones

Trifluoroacetic acid catalysed lactonization of vicinal disubstituted γ-hydroxyesters was investigated in different solvents. The reaction kinetics, monitored by NMR spectroscopy, showed that: (i) the vic-disubstituent effect is stereoselective since the anti diastereoisomer ring closes substantially more rapidly than the syn isomer ring; (ii) the anti-vic effect is much stronger than the classical Thorpe-Ingold effect (known also as the gem-disubstituent effect), instead the syn diastereoisomers have rate constants comparable to that of the gem-disubstituted ester; (iii) the vic-effect can be enhanced by increasing the steric hindrance of one of the two substituents or carrying out the reaction in non-polar solvents. DFT computations of energy barriers (ΔG?) were in good agreement with the experimental data. The distortion/interaction-activation strain model together with the Winstein-Holness kinetic scheme gave more insights into the origin of the vic-effect. An application of this effect consists of the diastereomeric resolution of disubstituted γ and δ lactones, among which are the naturally occurring Nicotiana t. lactone, the whisky and cognac oak lactones, and the Aerangis lactone. Both cis and trans diastereoisomers of these lactones were isolated in good yield and with high diastereomeric excess (de >92%). The selectivities of the diastereomeric resolution process, determined by NMR spectroscopy, are reported as well.

Lactones 42. Stereoselective enzymatic/microbial synthesis of optically active isomers of whisky lactone

Two different methods, enzyme-mediated reactions and biotrasformations with microorganisms, were applied to obtain optically pure cis- and trans-isomers of whisky lactone 4a and 4b. In the first method, eight alcohol dehydrogenases were investigated as biocatalysts to enantioselective oxidation of racemic erythro- and threo-3-methyloctane-1,4-diols (1a and 1b). Oxidation processes with three of them, alcohol dehydrogenases isolated from horse liver (HLADH) as well as recombinant from Escherichia coli and primary alcohol dehydrogenase (PADH I), were characterized by the highest degree of conversion with moderate enantioselectivity (ee = 27-82%) of the reaction. In all enzymatic reactions enantiomerically enriched not naturally occurring isomers of trans-(-)-(4R,5S)-4b or cis-(+)-(4R,5R)-4a were formed preferentially. In the second strategy, based on microbial lactonization of γ-oxoacids, naturally occurring opposite isomers of whisky lactones were obtained. Trans-(+)-(4S,5R)-isomer (ee = 99%) of whisky lactone 4b was stereoselectively formed as the only product of biotransformations of 3-methyl-4-oxooctanoic acid (5) catalyzed by Didimospheria igniaria KCH6651, Laetiporus sulphurens AM525, Chaetomium sp.1 KCH6670 and Saccharomyces cerevisiae AM464. Biotransformation of c-oxoacid 5, in the culture of Beauveria bassiana AM278 and Pycnidiella resinae KCH50 afforded a mixtures of trans-(+)-(4S,5R)-4b with enantiomeric excess ee = 99% and cis-(-)-(4S,5S)-4a with enantiomeric excesses ee = 77% and ee = 45% respectively.

An expedient synthesis of olfactory lactones by intramolecular hydroacylalkoxylation reactions

A series of 4,5-disubstituted γ-lactones, including whisky and cognac lactones, was synthesised in four steps from a readily available chiral precursor. By using an intramolecular hydroacylalkoxylation reaction in the final step, a correlation between the (E)/(Z) configuration of the precursor and the product distribution has been established, for the first time, in this type of cyclisation reactions. Copyright

Oxidative rearrangement of 2-alkoxy-3,4-dihydro-2H-pyrans: stereocontrolled synthesis of 4,5-cis-disubstituted tetrahydrofuranones including whisky and cognac lactones and crobarbatic acid

Oxidation of 2-alkoxy-3,4-dihydro-2H-pyrans 3 with dimethyldioxirane or MTO/urea-H2O2 followed by Jones oxidation leads to rearrangement and stereocontrolled formation of 4,5-cis-disubstituted tetrahydrofuranones. The method is applied to the synthesis of the whisky lactone 9, cognac lactone 10 and crobarbatic acid 17.

Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones

1-Alkenyl-1,1-heterobimetallics are potentially very useful in stereoselective organic synthesis but are relatively unexplored. Introduced herein is a practical application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of versatile cyclopropyl alcohol boronate esters, which are valuable building blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with dicyclohexylborane generates 1-alkenyl- 1,1-diboro species. In situ transmetalation with dialkylzinc reagents furnishes 1-alkenyl-1,1-borozinc heterobimetallic intermediates. Addition of the more reactive Zn-C bond to aldehydes generates the key B(pin) substituted allylic alkoxide intermediates. An in situ alkoxide directed cyclopropanation proceedswith the formation of two more C-C bonds, affording cyclopropyl alcohol boronate esters with three new stereocenters in 58-89percent isolated yields and excellent diastereoselectivities (>15:1 dr). Oxidation of the B-C bond provides trisubstituted α-hydroxycyclopropyl carbinols as single diastereomers in good to excellent yields (75-93percent). Facile pinacol-type rearrangement of the α-hydroxycyclopropyl carbinols provides access to both cis- and trans-2,3-disubstituted cyclobutanones with high stereoselectivity (>17:1 dr in most cases) from a common starting material. This methodology has been applied in the synthesis of quercus lactones A and B.

SN2′ boron-mediated Mitsunobu reactions - A new one-pot three-component synthesis of substituted enamides and enol benzoates

The conversion of (3-hydroxy-1-propen-1-yl)boronates to substituted enamides and enol benzoates is readily achieved in a one-pot procedure consisting of a regiocontrolled Mitsunobu reaction with convenient nucleophiles, followed by allylboration of aldehydes. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Oxidative rearrangement of 2-alkoxy-3,4-dihydro-2H-pyrans: Stereocontrolled synthesis of 4,5-cis-disubstituted tetrahydrofuranones

Oxidation of 2-alkoxy-3,4-dihydro-2H-pyrans with dimethyldioxirane followed by Jones oxidation leads to rearrangement and stereocontrolled formation of 4,5-cis-disubstituted tetrahydrofuranones; the method is applied to the synthesis of the whisky lactone 13 and cognac lactone 14.

Rates of formation of cis- and trans-oak lactone from 3-methyl-4- hydroxyoctanoic acid

The rates of formation of both cis- and trans-oak lactone from the corresponding isomers of 3-methyl-4-hydroxyoctanoic acid have been measured in model wine at room temperature for a range of pH values. The half-life for formation of the trans-isomer at pH 2.9 was calculated to be 3.1 h, whereas that for the cis-isomer, at the same pH, was calculated to be 40.5 h. The k trans/kcis ratio in model wine was found to 12.86 ± 1.34 over the range of pH values employed. A reason for the more facile formation of the trans-isomer, based on conformational reasons, has been proposed. In acidic aqueous media the equilibrium between the oak lactones and their corresponding ring-opened analogues was found to favor the former entirely, with no evidence for the latter being found. Implications of the present study for the future analysis of oak samples, as well as for the interpretation of existing data, are discussed.

Precursors to oak lactone. Part 2: Synthesis, separation and cleavage of several β-D-glucopyranosides of 3-methyl-4-hydroxyoctanoic acid

The β-D-glucopyranosides of all four stereoisomers of 3-methyl-4-hydroxyoctanoic acid have been prepared. The (3S,4S) and (3R,4R) species were prepared from cis-5-n-butyl-4-methyl-4,5-dihydro-2(3H)-furanone (cis-oak lactone) by a process involving ring-opening with base and protection of the carboxyl function as its benzyl ester. The glucose unit was introduced by a modified Koenigs-Knorr procedure. A different strategy was necessary for synthesis of the (3S,4R) and (3R,4S) compounds. This was based on the reductive ring-opening of trans-oak lactone and subsequent protection of the primary alcohol as its t-butyldiphenylsilyl ether. Separation of the individual glucosides was effected by preparative thin layer chromatography. Those corresponding to the nature-identical isomers of oak lactone have been shown to produce oak lactone under both acidic hydrolysis and pyrolysis conditions. The galloyl-β-D-glucoside of the cis-species, obtained as a natural isolate from the wood of Platycarya strobilacea, was also found to produce cis-oak lactone upon both acid hydrolysis and pyrolysis. Both the nature-identical (4S,5S) cis-oak lactone and its non-natural (4R,5R) enantiomer have been prepared from their corresponding glycosides and their aroma thresholds in white wine were determined to be 23 and 82 μg/L (ppb) respectively. The aroma threshold of the nature-identical isomer in a red wine was 46 μg/L.

Baker's yeast-mediated approach to (-)-cis- and (+)-trans-Aerangis lactones

The first enantioselective synthesis of natural (-)-cis-Aerangis lactone (-)-1a and its (+)-trans-diastereoisomer (+)-1b is described. The key steps in the synthesis are: (i) the enantiospecific and 100% diastereoselective baker's yeast reduction of 1,4-keto acid 2, to afford enantiopure trans-cognac lactone (+)-10; (ii) the regioselective PPL-mediated hydrolysis of the primary acetate moiety of diacetate (+)-(3S,4R)-3, obtained from (+)-10. Chain elongation by one carbon atom via cyanide substitution, and inversion of the configuration of C(5) in nitrile derivative (+)-21a are also required to complete the synthetic route to (-)-1a.