- 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.
- Brenna, Elisabetta,Dalla Santa, Francesco,Gatti, Francesco G.,Gatti, Giuseppe,Tessaro, Davide
-
p. 813 - 821
(2019/02/01)
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- 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.
- Boratyński, Filip,Smuga, Ma?gorzata,Wawrzeńczyk, Czes?aw
-
p. 419 - 427
(2013/10/08)
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- 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
- Adrio, Luis A.,Hii, King Kuok Mimi
-
p. 1852 - 1857
(2011/05/05)
-
- 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.
- Berree, Fabienne,Gernigon, Nicolas,Hercouet, Alain,Chia, Hui Lin,Carboni, Bertrand
-
supporting information; experimental part
p. 329 - 333
(2009/07/04)
-
- 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.
- Hussain, Mahmud M.,Li, Hongmei,Hussain, Nusrah,Urena, Mercedes,Carroll, Patrick J.,Walsh, Patrick J.
-
supporting information; experimental part
p. 6516 - 6524
(2009/09/26)
-
- 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.
- Armstrong, Alan,Ashraff, Cassim,Chung, Hunsuk,Murtagh, Lorraine
-
experimental part
p. 4490 - 4504
(2009/10/09)
-
- 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.
- Armstrong, Alan,Chung, Hunsuk
-
p. 1617 - 1619
(2007/10/03)
-
- 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.
- Wilkinson, Kerry L.,Elsey, Gordon M.,Prager, Rolf H.,Pollnitz, Alan P.,Sefton, Mark A.
-
p. 4213 - 4218
(2007/10/03)
-
- 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.
- Wilkinson, Kerry L.,Elsey, Gordon M.,Prager, Rolf H.,Tanaka, Takashi,Sefton, Mark A.
-
p. 6091 - 6100
(2007/10/03)
-
- 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.
- Brenna, Elisabetta,Negri, Claudia Dei,Fuganti, Claudio,Serra, Stefano
-
p. 1871 - 1879
(2007/10/03)
-
- Ruthenium-catalyzed cycloisomerization - Oxidation of homopropargyl alcohols. A new access to γ-butyrolactones
-
Vinylidenemetal species, which readily form from terminal alkynes under mild conditions, have rarely been utilized as reactive intermediates in a catalytic cycle. The conversion of homopropargyl alcohols via such intermediates to metal-complexed oxacarbenes led to the development of an oxidant compatible with a ruthenium complex capable of performing the cycloisomerization, that would convert them to lactones. None of the oxidants known to stoichiometrically convert isolated metallooxacarbenes to esters are effective. The unconventional oxidants , N-hydroxyimides, proved to be capable of effecting the desired transformation, with N-hydroxysuccinimide being the oxidant of choice. The procedure of choice employs cyclopentadienyl (1,4-cyclooctadiene) ruthenium chloride and trifuryl phosphine as the precatalyst in the presence of tetra-n-butylammonium bromide or hexafluorophosphate with N-hydroxysuccinimide as the oxidant in DMF-water at 95°. In this way, a wide diversity of homopropargyl alcohols were converted to γ-butyrolactones with excellent chemoselectivity. Lactones synthesized include an intermediate toward a platelet aggregation inhibitor, a fruit flavor principle, an inhibitor of binding of phorbol esters to PKC-α, a tobacco constituent, a wood constituent (quercus lactone), an aldosterone antagonist (spironolactone) precursor, and an acetogenin known for pesticidal and antitumor activities (muricatacin).
- Trost, Barry M.,Rhee, Young H.
-
p. 11680 - 11683
(2007/10/03)
-
- Ester Groups as Effective Ligands in Chelate-Controlled Additions of Cuprates and Grignard Reagents to Chiral β-Formyl Esters
-
Addition of cuprates to chiral methyl β-formyl carboxylates 1a-1d provided γ-lactones 2-7 in excellent trans-selectivity.The high diastereofacial selectivity was only obtained employing diethyl ether as solvent while tetrahydrofuran gave inferior results.Similar solvent effects were observed in the additions of various Grignard reagents to 1a, which afforded γ-lactones 2, 3, 12, and 13 in moderate trans-selectivity.The best solvent for these reactions was dichloromethane.The 1,3-induction of cuprate additions was studied by using aldehydes 8a-8c.The results obtained were interpreted in terms of chelate-controlled additions with formation of seven-membered ring chelates which involve both carbonyl functions of aldehyde 1 or 8.The function of ester groups as effective ligands of lithium or MgX cations may also be of importance for other stereoselective reactions employing organometallic reagents.
- Reissig, Hans-Ulrich,Angert, Hubert,Kunz, Thomas,Janowitz, Agnes,Handke, Gabriele,Bruce-Adjei, Emanuel
-
p. 6280 - 6285
(2007/10/02)
-
- NEW METHODS FOR REDUCTIVE FREE-RADICAL CYCLIZATIONS OF α-BROMOACETALS TO 2-ALKOXYTETRAHYDROFURANS WITH ACTIVATED CHROMIUM(II)-ACETATE
-
A method for the synthesis of γ-butyrolactones 6 is described in which the key step is a free-radical cyclization of α-bromoacetals 4 to 2-alkoxytetrahydrofurans 5 in 54-93percent yield induced by activated chromium(II)-acetate.Four new methods have been developed in order to activate the transition metal.Two of them require only catalytic amounts of chromium(II)-acetate, because it can be regenerated in situ chemically or electrochemically.The diastereoselectivity of the cyclization depends on the substitution pattern of 4 and ranges between 30.4:1 and 1:54.8.
- Hackmann, Claus,Schaefer, Hans J.
-
p. 4559 - 4574
(2007/10/02)
-
- A novel stereoselective route to γ-butyrolactones
-
Treatment of the products obtained from conjugate additions of sulfoxides to α,β-unsaturated carbonyl compounds with soft electrophiles resulted in intramolecular displacement of the sulfinyl group by the carbonyl to give γ-butyrolactones. This novel cyclisation works best for benzylic sulfoxides and provides a concise route to trans-β,γ-disubstituted lactones with high stereoselectivity.
- Casey,Manage,Murphy
-
p. 965 - 968
(2007/10/02)
-
- Sonochemical acceleration of conversion of 2-alkoxytetrahydrofurans to γ-butyrolactones synthesis of (±)-quercus lactone-A
-
Effect of sonochemical irradiation on the conversion of 2-alkoxytetrahydrofurans to γ-butyrolactones by Jones reagent, and its extension to the highly stereoselective synthesis of quercus lactone a, is reported.
- Srikrishna,Nagaraju,Sharma
-
p. 1127 - 1135
(2007/10/02)
-
- Synthesis of cis and trans Whisky and Cognac Lactones by the Regiocontrolled Alkylation of 2-(Trimethylsiloxy)furan
-
The racemic cis- and trans-5-butyltetrahydro-4-methylfuran-2-ones ( = whisky lactones) and their higher homologues tetrahydro-4-methyl-5-pentylfuran-2-ones ( = cognac lactones) have been prepared in 2-3 steps from 2(trimethylsiloxy)furan.Regioselective alkylation of the latter afforded the 5-butyl- and 5-pentylfuran-2(5H)-ones which served as precursors for the stereocontrolled construction of either diastereoisomer of the beverage lactones.The structure and tautomerization of the diazomethane adducts of these 5-alkylfuran-2(5H)-ones are also described.
- Jefford, Charles W.,Sledeski, Adam W.,Boukouvalas, John
-
p. 1362 - 1370
(2007/10/02)
-
- Dichotomous Regiochemistry of Aldehyde and Ketone in the Reaction with Dithio-Substituted Crotyllithium
-
The crotyllithium compound 1 generated from (E)-2-(1-propen-1-yl)-1,3-dithiane reacted with an aldehyde to give γ-products in favor of the anti isomer.This regio- and diastereoselective reaction is applicable to syntheses of trans β,γ-disubstituted γ-lactones, including natural products of (+/-)-eldanolide and (+/-)-trans quercus lactone.The γ(1,2)-adducts obtained from the reaction of 1 and enals underwent alkoxy-Cope rearrangements on treatment with KH.The consequence is virtually complete α(1,4)-addition of crotyllithium 1 to α,β-unsaturated aldehydes.Crotyllithium 1 reacted with ketones at either the α- or the γ-site, depending on the nature of respective ketone.The regiochemistry is well interpreted by the hard and soft acids and bases principle, when the steric effect is a minor controlling factor.The effects of HMPA and reaction temperature on the regioselectivity were also evaluated.
- Fang, Jim-Min,Hong, Bor-Cherng,Liao, Li-Fan
-
p. 855 - 861
(2007/10/02)
-
- Stereoisomeric Flavor Substances, XII. - 3-Methyl-4-octanolide - "Quercuslactone, Whiskylactone" - Structure and Properties of the Stereoisomeres
-
Ethyl 3-methyl-4-oxooctanoate (2) has been synthesized by reaction of pentanal with ethyl crotonate.Reduction with NaBH4 and cyclization yields racemic cis/trans-3-methyl-4-octanolide 1 which is separated to racemic cis (1a*1a') and trans (1b*1b') isomers by liquid chromatography.From 1a*1a' and 1b*1b' the diastereomers isopropyl (3R,4R)-, (3S,4S)-, (3S,4R)-, and (3R,4S)-4--3-methyloctanoates (3-6) and the diastereomers isopropyl (3R,4R)-, (3S,4S)-, (3S,4R)-, and (3R,4S)-4--3-methyloctanoates (7-10) have been synthesized and then separated by liquid chromatography.The absolute configurations of 1a, 1a', 1b and 1b' were derived from 1H-NMR data of 3-6 and optical activity could be estimated after recyclization into the optically active lactones 1a, 1a', 1b, and 1b'.From 7-10 optically pure stereoisomers of 1 have been obtained in preparative scale.Sensory characteristics of the stereoisomers are given.
- Guenther, Claus,Mosandl, Armin
-
p. 2112 - 2122
(2007/10/02)
-
- Diastereoselective Synthesis of cis- or trans-2,3-Substituted Tetrahydrofurans and 3,4-Substituted 4-Butanolides
-
Improved synthesis of 10 and the epimerisation 10 --> 11 yield cis- and trans-tetrahydro-3-furancarbaldehydes (10,11) with high diastereoselectivity. 10 as well as 11 are reduced by the Wolff-Kishner procedure to give 2-substituted 3-methyltetrahydrofurans 15 with trans configuration. 2-Substituted 3-methyltetrahydrofurans with cis configuration 14 are synthesized via 10 --> 12 --> 13 --> 14.The furans 14 and 15 possess structural features of naturally occurring 4-butanolides like quercus lactone a, quercus lactone b, or eldanolide which is the pheromone of the sugarcane borer Eldana saccharina (Wlk.). 14 and 15 are readily oxidized with CrO3/Ac2O to yield the lactones 16 and 17, whereas oxidation with Ru oxides proved to be less effective.The synthesis of rac-1 and rac-2 is described.
- Frauenrath, Herbert,Philipps, Thomas
-
p. 1951 - 1961
(2007/10/02)
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- A HIGHLY EFFICIENT METHOD FOR INTRODUCTION OF BUTENOLIDE MOIETIES TO VARIOUS ELECTROPHILES
-
Lithiated 5-(trimethylsilyl)furfuryl phenyl sulfides or the corresponding diphenylthioacetal can be used efficiently for introduction of butenolide moieties to various types of electrophilic reagents through their addition or substitution reactions followed by oxidation of the silylfuran moieties.
- Takano, Yasunobu,Yasuda, Akihiro,Urabe, Hirokazu,Kuwajima, Isao
-
p. 6225 - 6228
(2007/10/02)
-
- A DIASTEREOSELECTIVE SYNTHESIS OF BOTH QUERCUS LACTONE ISOMERS EMPLOYING ALLYL-TYPE ORGANOMETALLICS AS KEY INTERMEDIATES
-
Consecutive treatment of endo-butenyl potassium or endo-1-(tetrahydropyranyloxy)-exo-butenyl lithium with fluorodimethoxyboron and pentanal at -75 deg C affords an erythro- and, respectively, threo-adduct, the hydrolysis and oxidation of which leads to the cis- and,respectively, trans-isomer of 5-butyl-4-methyl-tetrahydro-2-furanone (4-butyl-3-methyl-4-butanolide), 1, the so called quercus or oak lactones.
- Moret, Etienne,Schlosser, Manfred
-
p. 4491 - 4494
(2007/10/02)
-
- HIGHLY DIASTEREOSELECTIVE SYNTHESIS OF DI-AND TRISUBSTITUTED 4-BUTANOLIDES FROM ALDEHYDES AND KETONES VIA THREE-CARBON-EXTENSION BY ALLYLIC HOMOENOLATE REAGENTS
-
Lithiated or titanated O-allyl carbamates 7 or 8 add to aldehydes and ketones regio- and diastereoselectively to yield-O-(4-hydroxy-1-alkenyl)carbamates 9, which are converted to γ-lactones 12 with an one-pot procedure.
- Hoppe, Dieter,Broenneke, Alfons
-
p. 1687 - 1690
(2007/10/02)
-