- Copper-catalyzed conjugate addition on macrocyclic, cyclic, and acyclic enones with a chiral phosphoramidite ligand having a C2-symmetric amine moiety
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A binaphthol-based phosphoramidite ligand (4.2 mol%) having a C2-symmetric chiral amine moiety was examined for enantioselective 1,4-additions of dialkylzinc reagents to various macrocyclic, cyclic, and acyclic enones catalyzed by copper triflate·toluene complex (2 mol%) to afford high enantiomeric excess (up to >95% ee).
- Choi, Yong Hyun,Choi, Jun Young,Yang, Hye Yon,Kim, Yong Hae
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- Efficient synthesis of (-)-(R)-muscone by enantioselective protonation
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A new synthesis of (-)-(R)-muscone ((R)-1) by means of enantioselective protonation of a bicyclic ketone enolate as the key step (see 6 → (S)-4 in Scheme 2) is presented. The C15 macrocyclic system is obtained by ozonolysis (Scheme 7).
- Fehr, Charles,Galindo, Jose,Farris, Iris,Cuenca, Ana
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- Ring closing metathesis guided synthesis of (R)-(-)-muscone
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A concise synthesis of the valuable perfumery compound (R)-(-)-muscone 1 in its natural form by making use of the ring closing olefin metathesis (RCM)-aided macrocyclisation route has been achieved.
- Kamat, Vijayendra P.,Hagiwara, Hisahiro,Suzuki, Toshio,Ando, Masayoshi
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- Cp2ZrMeCl: A Reagent for Asymmetric Methyl Addition
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The use of Cp2ZrMeCl is described as a source of nucleophilic methyl in asymmetric catalysis. This easily prepared reagent is bench stable, weighable in air, and generally useful in highly enantioselective copper-catalyzed addition reactions at room temperature. Methyl is successfully (generally >90% ee) added in 1,4-additions to cyclic and acyclic α,β-unsaturated ketones to provide tertiary and quaternary centers. Examples of catalyst controlled diastereoselective 1,6-addition and dynamic kinetic asymmetric allylic alkylation reactions are also reported. The reagent is used in the catalytic asymmetric synthesis of naturally occurring fragrance (R)-(-)-muscone (82% yield, 91% ee).
- Garrec, Kilian,Fletcher, Stephen P.
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- Deoxycholic acid-based phosphites as chiral ligands in the enantioselective conjugate addition of dialkylzincs to cyclic enones: Preparation of (-)-(R)-muscone
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Four phosphites, obtained by linking enantiomerically pure binaphthylchlorophosphite to the two different hydroxy substituted positions of deoxycholic acid, were used as chiral ligands in the enantioselective copper catalysed 1,4-addition of diethylzinc to 2-cyclohexenone and dimethylzinc to 2-cyclopentadecenone. Various reaction parameters were changed in order to select the experimental conditions that would maximise yield and ee. The four ligands were screened for activity and enantioselectivity under the optimised reaction conditions for comparative purposes, in order to establish the influence of the absolute configuration of the binaphthyl moiety as well as the position on the cholestanic backbone of the phosphite moiety. The ligand possessing a (R)-binaphthylphosphite moiety at position 12 of the cholestanic backbone proved to be the most enantioselective affording (-)-(R)-muscone in 63% ee.
- Iuliano, Anna,Scafato, Patrizia,Torchia, Rita
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- Asymmetric conjugate addition of metal alkyl reagents catalyzed by copper complexes with BINPO: A hemilabile P,O-heterobidentate axially chiral ligand
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We herein report the use of a new class of P,O-bidentate arylphosphine ligand for the asymmetric copper catalyzed conjugate addition of dialkylzinc and trialkylaluminium with the enantiomeric excesses reaching 91% while (R)-muscone was obtained with 77% ee.
- Fuchs, Nicolas,D'Augustin, Magali,Humam, Munir,Alexakis, Alexandre,Taras, Rossana,Gladiali, Serafino
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- Synthesis of (R)-(-)- and (S)-(+)-Muscone of 100percent Optical Purity by Conjugate Addition of Chiral Methylcuprate to (E)-Cyclopentadec-2-enone
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Synthesis of (R)-(-)- and (S)-(+)-muscone of essentially 100percent enantiomeric excess (e.e.) by the conjugate addition of chiral methylcuprate to (E)-cyclopentadec-2-enone was accomplished by adding small amounts of tetrahydrofuran (THF) as an external ligand to a toluene solution of the chiral methylcuprate.
- Tanaka, Kazuhiko,Suzuki, Hitomi
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- Synthesis of (R)-(-)-muscone via enzymatic resolution of 3- methylcyclopentadecan-1-ol
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(R)-(-)-Muscone was synthesized efficiently by oxidation of 3-(R)- methylcyclopentadecan-1-(RS)-ol, which was obtained by lipase-catalyzed resolution of its diastereomeric mixture.
- Matsumura, Yasufumi,Fukawa, Hidemichi,Terao, Yoshiyasu
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- Practical optical resolution of dl-muscone using tartaric acid derivatives as a chiral auxiliary
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A simple and practical synthesis of (R)-(-)-muscone was achieved by optical resolution of dl-muscone using tartaric acid derivatives. The acetalization of dl-muscone with N,N′-dibenzyl-l-tartaramide in the presence of Sc(OTf)3 and methyl orthoformate furnished a diastereomeric mixture of acetals, which were readily separated by simple recrystallization. Diastereomerically pure acetal was hydrolyzed to give optically pure muscone and recovered N,N′-dibenzyl-l-tartaramide.
- Takabe, Kunihiko,Sugiura, Masataka,Asumi, Yuya,Mase, Nobuyuki,Yoda, Hidemi,Shimizu, Hiroyasu
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- A novel synthetic method for (R)- and (S)-muscones by enantioselective hydrogenation of (E)- and (Z)-3-methyl-2-cyclopentadecen-1-ones catalyzed by p-tolyl-BINAP-Ru(II) complexes
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A novel and practical synthesis of (R)- and (S)-muscones by the asymmetric hydrogenation of (E)- and (Z)-3-methyl-2-cyclopentadecen-1-ones catalyzed by p-tolyl-BINAP-Ru(II) complexes has been achieved in nearly complete enantioselectivity.
- Yamamoto, Takeshi,Ogura, Miharu,Kanisawa, Tsuneyoshi
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- Asymmetric Synthesis of (R)-Muscone by Enantioselective Addition of Chiral Methyl Cuprate to (E)-2-Cyclopentadecen-1-one
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(R)-(-)-Muscone was prepared in 89percent enantiomeric excess using newly devised chiral ligands such as (1R,2R,3S,4S)-3--1,7,7-trimethylbicycloheptan-2-ol in conjugate addition of methyl cuprate to (E)-2-cyclopentadecen-1-one.
- Tanaka, Kazuhiko,Ushio, Hideki,Suzuki, Hitomi
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- Enantioselective routes to (-)-(R)-muscone
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The macrocyclic ring of muscone was prepared by Pd-catalyzed cyclization of hexadeca-1,15-diyne, which was converted to cyclopentadec-2-enone. The stereogenic center was introduced by enantioselective Cu-catalyzed conjugate addition of dimethylzinc. Because the ee in this step was only moderate, a new route via cyclopentadeca-2,14-dienone was developed. Enantioselective conjugate addition to this substrate led to 14-methylcylodec-2-enone, which was hydrogenated to give (-)-(R)-muscone in high overall yield with up to 98% ee. Georg Thieme Verlag Stuttgart.
- Bulic, Bruno,Lücking, Ulrich,Pfaltz, Andreas
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- Asymmetric activation of tropos catalysts in the stereoselective catalytic conjugate additions of R2Zn to α,β-enones: An efficient synthesis of (-)-muscone
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The preparation of a new phosphoramidite starting from (R)-BINOL and a biphenylamine is presented. In such a compound the chirality is due only to atropisomerism and this molecule possesses a flexible biphenylamine residue. Therefore it can work as a tropos catalyst. The catalytic efficiency of this new phosphoramidite has been tested in some asymmetric conjugate additions of dialkylzinc reagents to α,β-enones and compared with that of an analogous already known non-tropos ligand. Interestingly, while comparable results were obtained in the addition of ZnEt2 to chalcone and cyclohexenone, in the case of the addition of ZnMe2 to (E)-cyclopentadec-2-en-1-one, the new ligand provides (-)-muscone, a valuable ingredient of the perfume industry, in 84% ee, while the non-tropos ligand gives a much lower (57%) ee value. Graphical Abstract
- Scafato, Patrizia,Cunsolo, Giovanni,Labano, Stefania,Rosini, Carlo
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- Method for preparing chiral musk ketone
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A method for preparing chiral muscone is provided. 3-methyl-cyclopentadecane-1,5-dione is adopted as an initial raw material, chiral rhodium and a Br nsted acid are adopted as catalysts, hydrogen is adopted as a reductant, and a chiral muscone product is synthesized in a one-pot manner through asymmetric hydrogenation, hydrogenolysis and other reactions. The method is short and simple in route, high in total yield, low in generation of three types of waste and suitable for industrial production of the chiral muscone.
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Paragraph 0041; 0042
(2021/02/09)
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- Method for preparing L-muscone
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The invention discloses a method for preparing L-muscone. The method comprises the following steps: (1) L-muscone in racemic muscone and a chiral hydroxybenzene compound generate L-enantiomer salt under laser irradiation; and (2) crystallization separation and hydrolysis are performed on the L-enantiomer salt to obtain a L-muscone product, wherein the step (1) is carried out in the presence of a Bronsted acid catalyst. Preferably, after hydrolysis in the step (2), separation, purification and other steps are carried out to obtain the L-muscone product. The raw material used in the method is the racemic muscone with a mature production process; batch production can be realized, diastereomer salifying resolution is carried out by adopting laser irradiation, the product selectivity is greatlyimproved, the method is green, pollution-free, and less in production of three wastes, the chiral hydroxybenzene compound is convenient to recover and reusable, the atom economy is high, the productselectivity is high, and the method is suitable for being used in the fields of biology, medical treatment, medicines, spices, cosmetics and the like.
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Paragraph 0046; 0049
(2020/04/02)
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- Preparation method for L-muscone
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The invention provides a preparation method for L-muscone. Dehydrogenated muscone is taken as a starting material, chiral amine is taken as an inducer, homogeneous phase iridium is taken as a catalyst, hydrogen is taken as a reducing agent, and the L-muscone product is synthesized through imine synthesis, asymmetric hydrogenation and hydrolysis reaction. The homogeneous phase iridium catalyst usedin the method has low dose and low cost; the synthetic route has high total yield and few three wastes and is suitable for industrial production of L-muscone.
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Paragraph 0013; 0046; 0049
(2019/05/08)
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- (E)-3-METHYL-2-CYCLOALKENONE COMPOUND, 3-HALO-3-METHYLCYCLOALKANONE COMPOUND AND METHOD FOR PRODUCING (R)-3-METHYLCYCLOALKANONE COMPOUND
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PROBLEM TO BE SOLVED: To provide novel (E)-3-methyl-2-cycloalkenone compounds and 3-halo-3-methylcycloalkanone compounds, and also provide a production method that can efficiently produce (R)-3-methylcycloalkanone compounds. SOLUTION: An (E)-3-methyl-2-cycloalkenone compound has a chemical structure represented by the following formula (1) (where n is an integer of 1-5, 7 or 8). SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0268-0271; 0290; 0291
(2018/06/29)
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- METHOD FOR PRODUCING (Z)-3-METHYL-2-CYCLOPENTADECENONE AND METHOD FOR PRODUCING (R)-(-)-3-METHYLCYCLOPENTADECANONE
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PROBLEM TO BE SOLVED: To provide a (Z)-3-methyl-2-cyclopentadecenone production method capable of highly selectively producing (Z)-3-methyl-2-cyclopentadecenone at a low cost. SOLUTION: A (Z)-3-methyl-2-cyclopentadecenone production method includes an addition step of adding a hydrogen halide to 3-methyl-2-cyclopentadecenone and 3-methyl-3-cyclopentadecenone in a mixture comprising 3-methyl-2-cyclopentadecenone and 3-methyl-3-cyclopentadecenone. In addition, the production method includes a desorption step of desorbing the hydrogen halide from a hydrogen halide addition product after the addition step to isomerize (E)-3-methyl-2-cyclopentadecenone and 3-methyl-3-cyclopentadecenone to (Z)-3-methyl-2-cyclopentadecenone. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0062-0063; 0064; 0070; 0075
(2017/05/12)
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- Fluorinated Musk Fragrances: The CF2Group as a Conformational Bias Influencing the Odour of Civetone and (R)-Muscone
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The difluoromethylene (CF2) group has a strong tendency to adopt corner over edge locations in aliphatic macrocycles. In this study, the CF2group has been introduced into musk relevant macrocyclic ketones. Nine civetone and five muscone analogues have been prepared by synthesis for structure and odour comparisons. X-ray studies indeed show that the CF2groups influence ring structure and they give some insight into the preferred ring conformations, triggering a musk odour as determined in a professional perfumery environment. The historical conformational model of Bersuker and co-workers for musk fragrance generally holds, and structures that become distorted from this consensus, by the particular placement of the CF2groups, lose their musk fragrance and become less pleasant.
- Callejo, Ricardo,Corr, Michael J.,Yang, Mingyan,Wang, Mingan,Cordes, David B.,Slawin, Alexandra M. Z.,O'Hagan, David
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supporting information
p. 8137 - 8151
(2016/06/13)
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- Synthesis of (R)-(-)-muscone from (R)-5-bromo-4-methylpentanoate: A chiron approach
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A synthesis of (R)-muscone (1), a valuable musk odorant, is presented. The stereogenic center of muscone was introduced from methyl (R)-5-bromo-4-methylpentanoate (5), a chiral pool molecule developed in our group, and the macrocyclic ring was prepared by ring-closing metathesis (RCM) reaction. Using methyl (R)-5-bromo-4-methylpentanoate, we have accomplished a synthesis of (R)-muscone, a natural macrocyclic musk, based on chiral pool strategy.
- Shen, Junwei,Shi, Yong,Tian, Weisheng
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p. 683 - 687
(2015/06/25)
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- Exaltone (=Cyclopentadecanone) from Isomuscone (=Cyclohexadecanone), a one-C-atom ring-contraction methodology via a stereospecific favorskii rearrangement: Regioselective application to (-)-(R)-muscone
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Treatment of cyclohexadecanone (1g; with I2 (2.2 mol-euqiv.) and KOH in MeOH) furnished the unsaturated (Z)-ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further treatment with 3-chloroperbenzoic acid (m-CPBA) afforded the unreported epoxy ester 3g (88% yield), which was cleaved in 33% yield to Exaltone (=cyclopentadecanone; 1f) with NaOH in MeOH/H2O and then HCl at 65°. This methodology was similarly extended to higher (C17) and lower (C15 to C11) cyclic ketone analogues, as well as regioselectively to (-)-(R)-muscone (5c) and homomuscone (5f) (Scheme 2). Olfactive properties of the corresponding macrocyclic 1-oxaspiro[2,n]alkanes and -alkenes 4 and 8, resulting from a Coreyi-Chaykovsky oxiranylation, are also presented. Copyright
- Chapuis, Christian,Robvieux, Fabrice,Cantatore, Carole,Saint-Leger, Christine,Maggi, Laurent
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experimental part
p. 428 - 447
(2012/05/07)
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- PROCESS FOR PRODUCTION OF 3-METHYL-CYCLOPENTADECENONE, PROCESS FOR PRODUCTION OF R/S-MUSCONE, AND PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE MUSCONE
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By intramolecular condensation reaction of 2,15-hexadecanedione in a gaseous phase with a compound of a Group II element of the Periodic Table as a catalyst, 3-methyl-cyclopentadecenones is generated. Magnesium oxide, calcium oxide, or zinc oxide is desirable as the catalyst for the intramolecular condensation reaction. (R)- and (S)-muscone is generated by subjecting 3-methyl-cyclopentadecenones obtained as above to hydrogenation by using a catalyst. Palladium catalyst is desirable as the hydrogenation catalyst. Optically active muscone is generated by separating 3-methyl-cyclopentadecenones into respective components thereof by means of precision distillation and subsequently subjecting the separated 3-methyl-cyclopentadecenones to asymmetric hydrogenation by using an optically active ruthenium complex catalyst. The production methods described above enable easy and economical production of 3-methyl-cyclopentadecenones, (R)-and (S)-muscone, and optically active muscone.
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(2012/02/14)
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- METHOD FOR PRODUCING 3-METHYL-CYCLOPENTADECENONES, METHOD FOR PRODUCING (R)- AND (S)- MUSCONE, AND METHOD FOR PRODUCING OPTICALLY ACTIVE MUSCONE
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By intramolecular condensation reaction of 2,15-hexadecanedione in a gaseous phase with a compound of a Group II element of the Periodic Table as a catalyst, 3-methyl-cyclopentadecenones is generated. Magnesium oxide, calcium oxide, or zinc oxide is desirable as the catalyst for the intramolecular condensation reaction. (R)- and (S)-muscone is generated by subjecting 3-methyl-cyclopentadecenones obtained as above to hydrogenation by using a catalyst. Palladium catalyst is desirable as the hydrogenation catalyst. Optically active muscone is generated by separating 3-methyl-cyclopentadecenones into respective components thereof by means of precision distillation and subsequently subjecting the separated 3-methyl-cyclopentadecenones to asymmetric hydrogenation by using an optically active ruthenium complex catalyst. The production methods described above enable easy and economical production of 3-methyl-cyclopentadecenones, (R)- and (S)-muscone, and optically active muscone.
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(2011/08/03)
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- A practical synthesis of (rac)-muscone and (R)-(-)-muscone
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A practical synthesis of (rac)-muscone in three steps is described, using commercially available 1,10-dibromodecane as the starting material. In the first step, an aldol reaction of 1,10-dibromodecane with ethyl acetoacetate affords the important intermediate 2,15-hexadecanedione in 70% yield. A cyclisation reaction in the second step aided by propyl zinc iodide gives dehydro-muscone in 84% yield. Hydrogenation of dehydro-muscone with Pd-C completes the synthesis of (rac)-muscone. Furthermore, (R)-(-)-muscone is enantioselectively prepared via the formation of a ketal intermediate from dehydro-muscone and 1,4-di-O-benzyl-D-threitol.
- Cheng, Chuanjie,Ding, Wei,Ding, Shaomin
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p. 195 - 197
(2011/07/30)
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- Catalytic asymmetric michael reactions of α,β-unsaturated ketones with sulfonyl-containing nucleophiles: Chiral synthesis of (R)-muscone and (S)-celery ketone
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An amine worth its salt: A highly enantioselective Michael addition reaction of α,β-unsaturated ketones with the sulfonyl-containing nucleophiles bis(phenylsulfonyl)methane and 1-(phenylsulfonyl)propan-2-one, catalyzed by a chiral primary amine salt, has been developed and gives excellent enantioselectivities (see scheme). The methodology has successfully demonstrated its synthetic utility in the chiral synthesis of (R)-muscone and (S)-celery ketone.
- Sun, Xiaomin,Yu, Feng,Ye, Tingting,Liang, Xinmiao,Ye, Jinxing
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supporting information; experimental part
p. 430 - 434
(2011/03/18)
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- (+)-(R,Z)-5-Muscenone and (-)-(R)-Muscone by enantioselective aldol reaction and grob fragmentation
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(+)-(R,Z)-5-Muscenone ((R)-1) was synthesized by an enantioselective aldol reaction, catalyzed by new ephedrine-type Ti reagents (up to 70% enantiomeric excess). Substrate-directed diastereoselective reduction of the aldol product and Grob fragmentation of the tosylate of the resultant 1,3-diol afforded (+)-1. This approach also gave access to (-)-(R,E)-5-muscenone and (-)-(R)-muscone.
- Fehr, Charles,Buzas, Andrea K.,Knopff, Oliver,De Saint Laumer, Jean-Yves
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experimental part
p. 2487 - 2495
(2010/06/16)
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- Olefinic-lactone cyclizations to macrocycles
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(Chemical Equation Presented) Olefinic-lactone cyclization reactions that result in the generation of macrocycles are described.
- Rohanna, John C.,Rainier, Jon D.
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supporting information; experimental part
p. 493 - 495
(2009/08/15)
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- PROCESS FOR PRODUCING LARGE CYCLIC KETONE AND INTERMEDIATE THEREFOR
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A process for producing muscone by methyl addition to the 1,4-conjugation of 2-cyclopentadecenone. By the process, muscone is produced in high yield not under reaction condition including an extremely low temperature and a low concentration but under practical condition. The process comprises subjecting 2-cyclopentadecenone to a 1,4-conjugation addition reaction with an organometallic methylation reagent in the presence of a copper or nickel catalyst and an enol anion scavenger to obtain a 3-methyl-1-cyclopentadecene derivative represented by General Formula (II) and then solvolyzing the enol moiety of the 3-methyl-1-cyclopentadecene derivative to obtain muscone.
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- Stereoselective and enantioselective syntheses of the four stereoisomers of muscol from (3RS)-muscone
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Two trans stereoisomers of 3-methylcyclopentadecanol (= muscol), (1R,3R)-2 and (1S,3S)-2, were efficiently synthesized from (3RS)-3- methylcyclopentadecanone (= muscone; (3RS)-1) by a highly stereoselective reduction (Scheme). L-Selectride (= lithium tri(sec-butyl)borohydride) was used, followed by the enantiomer resolution by lipase QLG (Alcaligenes sp.). The cis stereoisomers of muscol, (1S,3R)-2 and (1R,3S)-2, were obtained by the Mitsunobu inversion of (1R,3R)-2 and (1S,3S)-2, respectively (Scheme). The absolute configuration of (1R,3R)-2 was determined by X-ray crystal-structure analysis of its 3-nitrophthalic acid monoester, 2-[(1R,3R)-3- methylcyclopentadecyl hydrogen benzene-1,2-dicarboxylate ((1R,3R)-3b), and by oxidation of (1R,3R)-2 to (3R)-muscone.
- Yuasa, Yoshifumi,Fukaya, Haruhiko,Yuasa, Yoko
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p. 977 - 982
(2008/02/04)
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- OPTICALLY ACTIVE 3-METHYLCYCLOPENTADECANONE AND METHOD FOR PRODUCING INTERMEDIATE THEREOF
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Disclosed is a method for producing an optically active 3-methylcyclopentadecan-1-one which is characterized in that 2-cyclopentadecen-1-one is subjected to a 1,4-conjugate addition reaction of a methyl group by using a methylated organic metal in the presence of a copper catalyst, an enol anion scavenger and a specific optically active phosphoramidite for obtaining an optically active 3-methyl-1-cyclopentadecene derivative, and then the thus-obtained 3-methyl-1-cyclopentadecene derivative is subjected to a solvolysis.
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(2008/06/13)
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- PROCESS FOR PRODUCING LARGE CYCLIC KETONE AND INTERMEDIATE THEREFOR
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A process for producing muscone by methyl addition to the 1,4-conjugation of 2-cyclopentadecenone. By the process, muscone is produced in high yield not under reaction conditions including an extremely low temperature and a low concentration but under practical conditions. The process comprises subjecting 2-cyclopentadecenone to a 1,4-conjugation addition reaction with an organometallic methylation reagent in the presence of a copper catalyst or nickel catalyst and an enol anion-trapping agent to obtain a 3-methyl-1-cyclopentadecene derivative represented by the general formula (II): (II) and then solvolyzing the enol moiety of this 3-methyl-1-cyclopentadecene derivative to obtain muscone.
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(2008/06/13)
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- Process for producing muscone and its intermediate
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The present invention provides a process for producing a muscone represented by (1) by subjecting a citronellic acid derivative and an undecenoate to a Claisen condensation reaction to produce a keto ester compound represented by (2) decarboxylating the keto ester compound to produce 2,6-dimethyl-8-oxy-2,17-heptadecadiene, cyclizing the heptadecadiene using a metathesis catalyst to produce a 6-dehydromuscone represented by (3) and then hydrogenating the double bond. The present invention also provides the keto ester compound.
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Page/Page column 7
(2008/06/13)
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- A simplified synthesis of (R)-(-)-muscone using a ring-opening reaction of (R)-(+)-β-methyl-β-propiolactone
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A chiral macrocyclic precursor can be constructed via a ring-opening reaction of (R)-(+)-β-methyl-β-propiolactone with a functionalized organocuprate with no loss of enantiomeric excess. The carboxylic acid precursor was used as a chiral building block for the synthesis of chiral muscone and musky macrolactones.
- Morita, Motoaki,Mase, Nobuyuki,Yoda, Hidemi,Takabe, Kunihiko
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p. 3176 - 3182
(2007/10/03)
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- Ti-Crossed-Claisen condensation between carboxylic esters and acid chlorides or acids: A highly selective and general method for the preparation of various β-keto esters
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Ti-crossed-Claisen condensation between a 1:1 mixture of carboxylic esters and acid chlorides promoted by TiCl4-Bu3N-N-methylimidazole proceeded successfully to give various β-keto esters in good yields with excellent selectivities (19 examples, ~48-95% yield; cross/self-selectivity = ~96/4-99/1). The present method was extended to the condensation between a 1:1 mixture of carboxylic acids and carboxylic esters (six examples, ~70-92% yield; cross/self-selectivity = ~91/9-99/1). To demonstrate the utility of the present two Ti-crossed-Claisen condensations, we performed a couple of efficient short-step syntheses of two natural, representative, and useful perfumes, cis-jasmone and (R)-muscone. Copyright
- Misaki, Tomonori,Nagase, Ryohei,Matsumoto, Kunshi,Tanabe, Yoo
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p. 2854 - 2855
(2007/10/03)
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- Cp*Ru(PN) complex-catalyzed isomerization of allylic alcohols and its application to the asymmetric synthesis of muscone
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Highly efficient isomerization of allylic alcohols into saturated carbonyls is accomplished using the catalyst system of Cp*RuCl[Ph2P(CH2)2NH2-κ2-P,N]-KOt-Bu (Cp* = η5-C5(CH3)5) under mild conditions. Mechanistic consideration based on isotope-labeling experiments indicated the present reaction is applicable to the asymmetric isomerization of racemic sec-allylic alcohols with a prochiral olefin via dynamic kinetic resolution. A concise asymmetric synthesis of muscone has been achieved, where the asymmetric isomerization using an optically active ligand is a key reaction. Copyright
- Ito, Masato,Kitahara, Sachiko,Ikariya, Takao
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p. 6172 - 6173
(2007/10/03)
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- An efficient enantioselective synthesis of (+)-(R,Z)-5-muscenone and (-)-(R)-muscone - An example of a kinetic resolution and enantioconvergent transformation
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An efficient catalytic kinetic resolution by CBS reduction and an original enantioconvergent transformation involving a PdII-catalyzed position-selective cyclization are the key steps for the synthesis of the exceptional musk odorant (R,Z)-5-muscenone [(R)-1] and (R)-muscone [(R)-3]. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Fehr, Charles,Galindo, Jose,Etter, Olivier
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p. 1953 - 1957
(2007/10/03)
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- Highly enantioselective conjugate addition of AlMe3 to linear aliphatic enones by a designed catalyst
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2-Hydroxy-2′-alkylthio-1,1′-binaphthy compounds are catalytic promoters of the 1,4-addition of AlMe3 to linear aliphatic enones in THF at -40 to -48°C in the presence of [Cu(MeCN)4]BF4. At ligand loadings of 5-20 mol%, enantioselectivities of 80-93% are realised for most substrates. To attain these values, the use of highly pure AlMe3 is mandatory. The presence of methylalumoxane (MAO), derived by hydrolysis, leads to reduced enantioselectivity and a conjugate addition product.
- Fraser, Paul K.,Woodward, Simon
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p. 776 - 783
(2007/10/03)
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- Catalytic enantioselective conjugate addition of dialkyl zinc reagents to α,β-unsaturated ketones mediated by new phosphite ligands containing binaphthalene/1,2-diphenylethane moieties: A practical synthesis of (R)-(-)-muscone
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New diastereoisomeric phosphites based on either (R)- or (S)-2,2′-dihydroxy-1,1′-binaphthyl (BINOL) and having the chiral alcoholic moiety derived from the monobenzyl ether of (R,R)-1,2-diphenylethane- 1,2-diol have been prepared and used as chiral ligands in the enantioselective copper-catalyzed 1,4-addition of diethylzinc to chalcone and 2-cyclohexen-1-one (enantiomeric excesses up to 48%). With the (aR,R,R) ligand dimethylzinc adds enantioselectively to (E)-cyclopentadecen-2-en-1-one to give (R)-(-)-muscone (68% yield, 78% ee). This provides an efficient access to a valuable ingredient of the perfume industry. However, with the (aS,R,R) ligand, (S)-(+)-muscone is obtained with longer reaction times (37% yield and 10% ee) with a very high double diastereoselection effect being observed.
- Scafato, Patrizia,Labano, Stefania,Cunsolo, Giovanni,Rosini, Carlo
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p. 3873 - 3877
(2007/10/03)
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- Synthesis of (R)- and (S)- muscone
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(R)-(-)-Muscone (3-methylcyclopentadecanone, 1) the key perfumery component isolated from the male musk deer, Moschus moschiferus,* was synthesized from the easily available chiral building block, (R)-3-tert-butoxycarbonyl-2- methylpropanoic acid (2), by employing ring-closing olefin metathesis (RCM). Antipode (+)-1 was also synthesized in a similar manner from tert-butyl (S)-3-methoxycarbonylbutanoate (10). *(a) Walbaum, H. J. J. Prakt. Chem., 73, 488 (1906); (b) Ruzicka, L., Further considerations on the constitution of muscone. Helv. Chim. Acta, 9, 715, 1008-1017 (1926).
- Fujimoto, Satoko,Yoshikawa, Keisuke,Itoh, Masamichi,Kitahara, Takeshi
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p. 1389 - 1392
(2007/10/03)
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- Ring closing metathesis directed synthesis of (R)-(-)-muscone from (+)- citronellal
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A concise and simple synthesis of the valuable perfumery ingredient (R)- (-)-muscone 1 has been achieved through ring closing olefin metathesis (RCM) aided macrocyclization protocol as the key step. Commercially available starting material (R)-(+)-citronellal 3 has been employed as a building unit in preparing the acyclic diolefinic substrate 16, which in turn was exposed to bis(tricyclohexylphosphine)benzylideneruthenium dichloride catalyst 2 to afford the cyclic RCM reaction product 17 in 78% yield. Catalytic hydrogenation of 17 furnished enantiomerically pure (R)-(-)-muscone 1. (C) 2000 Elsevier Science Ltd.
- Kamat, Vijayendra P.,Hagiwara, Hisahiro,Katsumi, Tomoko,Hoshi, Takashi,Suzuki, Toshio,Ando, Masayoshi
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p. 4397 - 4403
(2007/10/03)
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- Chiral Amplification and the Catalytic Process in the Enantioselective Conjugate Addition of Chiral Alkoxydimethylcuprate to (E)-Cyclopentadec-2-en-1-one
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The stoichiometric conjugate addition with 60percent enantiomeric excess (e.e.), of a chiral alkoxydimethylcuprate prepared from an 80:20 mixture of (1R,2R,3S,4S)-3--1,7,7-trimethylbicycloheptan-2-ol and its enantiomer , to (E)-cyclopentdec-2-en-1-one 1 produced (R)-(-)-muscone 2 in 76percent e.e. and 82percent chemical yield.This chiral amplification can be explained by considering that the reaction proceeds via a homochiral dimeric cluster of the chiral alkoxydimethylcuprate.The catalytic conjugate addition was realized by adding methyllithium and the enone alternately to a toluene solution of the chiral alkoxydimethylcuprate prepared from a catalytic amount of the chiral ligand and copper(I) salt. (R)-(-)-Muscone with 99percent optical purity was obtained in 85percent chemical yield by the use of 0.36 equiv. of endo-(+)-MPATH and 0.33 equiv. of copper(I) iodide.This methodology provides not only the highest enentioselectivity, but also useful information on the structure and mechanism of the conjugate addition of the organocuprate prepared from the copper(I) salt and alkyllithium.
- Tanaka, Kazuhiko,Matsui, Junichi,Suzuki, Hitomi
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p. 153 - 158
(2007/10/02)
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- Catalytic Enantioselective Conjugate Addition of Chiral Alkoxydimethylcuprate to (E)-Cyclopentadec-2-enone
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Asymmetric 1,4-addition of methyllithium to (E)-cyclopentadec-2-enone was promoted by the chiral cuprate catalyst prepared from (1R,2R,3S,4S)-3--1,7,7-trimethylbicycloheptan-2-ol and copper(I) iodide to give (R)-(-)-muscone in 76percent chemical yield and 96percent enantiomeric excess.
- Tanaka, Kazuhiko,Matsui, Junichi,Suzuki, Hitomi,Watanabe, Akio
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p. 1193 - 1194
(2007/10/02)
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- Asymmetric Syntheses of (R)-(-)-Muscone based on Diastereoselective Conjugate Addition
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(R)-(-)-Muscone was synthesized in a stereocontrolled manner via the stereoselective conjugate addition to a cyclic α,β-unsatureted ester of (R,R)-cyclohexane-1,2-diol accompanied by spontaneous Dieckmann condensation.
- Ogawa, Tomoyuki,Fang, Cheng-Lin,Suemune, Hiroshi,Sakai, Kiyoshi
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p. 1438 - 1439
(2007/10/02)
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- Asymmetric Synthesis of (R)-(-)- and (S)-(+)-Muscone by Enantioselective Conjugate Addition of Chiral Dimethylcuprate to (E)-Cyclopentadec-2-en-1-one
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A variety of optically active secondary amino alcohols have been prepared from camphor and screened as chiral non-transferable cuprate ligands in conjugate addition reactions.The reactions of (E)-cyclopentadec-2-en-1-one with chiral dimethylcuprates derived from the ligand in toluene afforded muscone in enantiomeric excesses as high as 26 - 89 percent.The stereochemistry of the product correlates with the configuration of the chiral ligand used.Thus the conjugate addition using the ligand prepared from exo-3-monosubstituted-amino-exo-2-hydroxybornane gave (S)-(+)-muscone, while with endo-ligand, (R)-(-)-muscone was obtained in higher enantioselectivity.Muscone of essentially 100percent optical purity was obtained by the addition of small amounts of THF (tetrahydrofuran) (2 - 10 equiv.) to the toluene solution of the chiral cuprate reagent prepared from (1R,2R,3S,4S)-3--1,7,7-trimethylbicycloheptan-2-ol 23 (endo-MPATH).The effect of the stoichiometry of the chiral ligand and the cuprate reagent on the chemical yield and enantioselectivity was briefly investigated.
- Tanaka, Kazuhiko,Ushio, Hideki,Kawabata, Yasuyuki,Suzuki, Hitomi
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p. 1445 - 1452
(2007/10/02)
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- Construction of Medium- and Large-Sized Cyclic β-Keto Esters (or Nitriles) via One-Pot Three-Carbon Ring Expansion of Carbocyclic β-Keto Esters and Its Application to the Synthesis of (-)-Muscone
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A one pot, three-carbon ring expansion involving intramolecular aldol condensation and subsequent retro-aldol cleavage is induced by treatment of β-keto esters with potassium tert-butoxide in dimethyl sulfoxide to afford functionalized 8-,9-,10-, and 15-membered rings, respectively.The stereochemistry of intermediate 21 was established to be a cis-fused carbocyclic ring system with the methyl ketone in the cis position.The mechanism for the three-carbon ring expansion is explained by considering the dual function of the electron-withdrawing group (EWG).An iterativering expansion was accomplished by the facile conversion of 8 to 20.Application of this ring expansion method to the synthesis of (-)-muscone further attests to the generality of this reaction.
- Xie, Zhuo-Feng,Sakai, Kiyoshi
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p. 820 - 826
(2007/10/02)
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- Homochiral Ketals in Organic Synthesis. Enantioselective Synthesis of (R)-Muscone
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An efficient, enantioselective preparation of (R)-muscone employing a diastereoselective Simmons-Smith cyclopropanation is described.Cyclopropanation is directed via chelation control by a homochiral ketal protecting group derived from unnatural tartaric acid.The overall yield of (R)-muscone (>95percent R) from commercially available cyclopentadecanone is 60percent over seven steps.
- Nelson, Keith A.,Mash, Eugene A.
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p. 2721 - 2724
(2007/10/02)
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