- Catalytic Asymmetric Acyloin Rearrangements of α-Ketols, α-Hydroxy Aldehydes, and α-Iminols by N, N′-Dioxide-Metal Complexes
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A highly enantioselective acyloin rearrangement of cyclic α-ketols has been developed with a chiral Al(III)-N,N′-dioxide complex as catalyst. This strategy provided an array of optically active 2-acyl-2-hydroxy cyclohexanones in moderate to good yields with high enantioselectivities. The asymmetric isomerizations of acyclic α-hydroxy aldehydes and α-iminols were achieved as well under modified conditions, affording the corresponding chiral α-hydroxy ketones and α-amino ketones in moderate results. Moreover, further transformations of product to enantioenriched diols were carried out.
- Dai, Li,Li, Xiangqiang,Zeng, Zi,Dong, Shunxi,Zhou, Yuqiao,Liu, Xiaohua,Feng, Xiaoming
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p. 5041 - 5045
(2020/07/03)
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- Direct Asymmetric α-Hydroxylation of Cyclic α-Branched Ketones through Enol Catalysis
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Enantiopure α-hydroxy carbonyl compounds are common scaffolds in natural products and pharmaceuticals. Although indirect approaches towards their synthesis are known, direct asymmetric methodologies are scarce. Herein, we report the first direct asymmetric α-hydroxylation of α-branched ketones through enol catalysis, enabling a facile access to valuable α-keto tertiary alcohols. The transformation, characterized by the use of nitrosobenzene as the oxidant and a new chiral phosphoric acid as the catalyst, delivers a good scope and excellent enantioselectivities.
- Shevchenko, Grigory A.,Pupo, Gabriele,List, Benjamin
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- An Unexpected α-Oxidation of Cyclic Ketones with 1,4-Benzoquinone by Enol Catalysis
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The first direct and asymmetric α-aryloxylation of cyclic ketones via enol catalysis has been achieved using quinones as the reaction partners. Catalytic amounts of a phosphoric acid promote the exclusive formation of α,α-disubstituted ketones from the corresponding α-substituted ketones in good yields and enantioselectivities (up to 96.5:3.5 er). Preliminary mechanistic experiments suggest that this reaction proceeds via a proton-coupled electron transfer (PCET) followed by radical recombination.
- Shevchenko, Grigory A.,Oppelaar, Barry,List, Benjamin
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p. 10756 - 10759
(2018/08/17)
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- Synthesis of tetrahydrobiphenylene via Pd(0)-catalyzed C(sp2)-H functionalization
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Tetrahydrobiphenylene consists of cyclobutene fused with benzene and cyclohexene rings. In this paper, a direct method for synthesizing tetrahydrobiphenylenes based on a palladium (Pd)(0)-catalyzed C(sp2)-H functionalization was investigated. The developed method was applied to the synthesis of several tetrahydrobiphenylenes having an oxygen functionality at the ring juncture. The derivatization of a tetrahydrobiphenylene is also reported.
- Tsukano, Chihiro,Suetsugu, Satoshi,Muto, Nobusuke,Takemoto, Yoshiji
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p. 1167 - 1174
(2018/05/02)
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- Iron(iii) chloride hexahydrate-promoted selective hydroxylation and chlorination of benzyl ketone derivatives for the construction of hetero-quaternary scaffolds
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A novel and tunable α-hydroxylation/α-chlorination of benzyl ketone derivatives has been developed for the construction of hetero-quaternary carbon centers by iron(iii) chloride hexahydrate mediated selective transformations through the application of dif
- Chen, Tao,Peng, Rui,Hu, Wenxin,Zhang, Fu-Min
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supporting information
p. 9859 - 9867
(2016/10/31)
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- Oxidative cleavage of olefins by in situ-generated catalytic 3,4,5,6-tetramethyl-2-iodoxybenzoic acid/oxone
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Oxidative cleavage of a variety of olefins to the corresponding ketones/carboxylic acids is shown to occur in a facile manner with 3,4,5,6-tetramethyl-2-iodobenzoic acid (TetMe-IA)/oxone. The simple methodology involves mere stirring of the olefin and catalytic amount (10 mol %) of TetMe-IA and oxone in acetonitrile-water mixture (1:1, v/v) at rt. The reaction mechanism involves initial dihydroxylation of the olefin with oxone, oxidative cleavage by the in situ-generated 3,4,5,6-tetramethyl-2-iodoxybenzoic acid (TetMe-IBX), and oxidation of the aldehyde functionality to the corresponding acid with oxone. Differences in the reactivities of electron-rich and electron-poor double bonds have been exploited to demonstrate chemoselective oxidative cleavage in substrates containing two double bonds.
- Moorthy, Jarugu Narasimha,Parida, Keshaba Nanda
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p. 11431 - 11439
(2015/02/05)
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- Enantioselective titanium(III)-catalyzed reductive cyclization of ketonitriles
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Reduction, please! The title reaction affords ?-hydroxyketones, a common structural motif in biologically active natural products, in good yields and high enantioselectivities at room temperature. The commercially available ansa-titanocene 1 was found to be an efficient catalyst for this process, which presumably proceeds by addition of a ketyl radical to a nitrile.
- Streuff, Jan,Feurer, Markus,Bichovski, Plamen,Frey, Georg,Gellrich, Urs
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supporting information; experimental part
p. 8661 - 8664
(2012/09/21)
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- Improved methods for thermal rearrangement of alicyclic α-hydroxyimines to α-aminoketones: Synthesis of ketamine analogues as antisepsis candidates
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Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low doses of ketamine administrated to patients before incision significantly reduced post-operative inflammation as reflected by reduced interleukin-6 (IL-6) sera-levels. Our data demonstrated in a rat model of Gram-negative bacterial-sepsis that if we inject a low dose of ketamine following bacterial inoculation we reduce mortality from approximately 75% to 25%. Similar to what we have observed in operated patients, the levels of TNF-α and IL-6 in ketamine-treated rats were significantly lower than in septic animals not treated with ketamine. On the base of these results, we have designed and synthesized series of new analogues of ketamine applying a thermal rearrangement of alicyclic α-hydroxyimines to α-aminoketones in parallel arrays. One of the analogues (compound 6e) displayed high activity in down-regulating the levels of IL-6 and TNF-α in vivo as compared to ketamine.
- Elhawi, Hagit,Eini, Hadar,Douvdevani, Amos,Byk, Gerardo
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p. 6784 - 6807
(2012/09/07)
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- Mg-promoted facile and selective intramolecular cyclization of aromatic δ-ketoesters
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Treatment of various types of aromatic δ-ketoesters 2, 7, and 9 with Mg-turnings for Grignard reaction at -5 to 0 °C in N,N-dimethylformamide (DMF) containing trimethylsilyl chloride (TMSCl) brought about selective and reductive intramolecular cyclization
- Miyazaki, Takeshi,Maekawa, Hirofumi,Yonemura, Kazuaki,Yamamoto, Yoshimasa,Yamanaka, Yoshiko,Nishiguchi, Ikuzo
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experimental part
p. 1598 - 1602
(2011/03/22)
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- Asymmetric electrochemical oxidation of 1,2-diols, aminoalcohols, and?aminoaldehydes in the presence of chiral copper catalyst
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Asymmetric oxidation of 1,2-diols, aminoalcohols, and aminoaldehydes in the presence of copper(II) triflate and (R,R)-Ph-BOX was accomplished by electrochemical method using Br- as a mediator. This oxidation was applicable to kinetic resolution of racemic cis-cycloalkane-1,2-diols, aminoalcohols, and aminoaldehydes to afford optically active compounds with good to high enantioselectivity.
- Minato, Daishirou,Arimoto, Hitomi,Nagasue, Yoko,Demizu, Yosuke,Onomura, Osamu
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p. 6675 - 6683
(2008/12/20)
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- Asymmetric oxidation of 1,2-diols using N-bromosuccinimide in the presence of chiral copper catalyst
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Asymmetric oxidation of 1,2-diols using N-bromosuccinimide (NBS) in the presence of copper(II) triflate and (R,R)-Ph-BOX has been exploited. This oxidation was applicable to asymmetric desymmetrization of meso-hydrobenzoin and kinetic resolution of dl-hydrobenzoin and racemic-cycloalkane-cis-1,2-diols to afford optically active α-ketoalcohols with good to high enantiomeric excess.
- Onomura, Osamu,Arimoto, Hitomi,Matsumura, Yoshihiro,Demizu, Yosuke
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p. 8668 - 8672
(2008/04/13)
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- Oxidative cleavage of vicinal diols: IBX can do what Dess-Martin periodinane (DMP) can
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A study was conducted to demonstrate the similarity of reactivity between o-iodoxybenzoic acid (IBX), an oxidative agent of vicinal diols and Des-Martin periodinane (DMP). The study examined IBX-mediated oxidative cleavage of tert,tert-1,2-diols and discovered pathways that favored fragmentation of sec,sec-1,2-diols, which produce non-cleavage products. It was observed that IBX can be employed to perform oxidative cleavage of 1,2-diols similar to DMP by simple variation of solvent and temperature. It was also observed that protonation of 10-1-4 species of diols may suppress the nucleophilic attack, leading to the production of ketol to achieve oxidative cleavage of sec,sec-1,2-diols that yield non-cleavage products with IBX in DMSO. TFA was used as a significant source of protons and a better solvent of IBX to conduct protonation of diols. A variety of sec,sec,tert,tert and sec,tert syn-1,2-diols underwent oxidative cleavage effectively, using TFA as a solvent.
- Moorthy, Jarugu Narasimha,Singhal, Nidhi,Senapati, Kalyan
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p. 767 - 771
(2008/03/27)
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- Electroreductive acylation of aromatic ketones with acylimidazoles
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The intermolecular reductive coupling of aromatic ketones with acylimidazoles was effected by electroreduction in the presence of chlorotrimethylsilane and gave α-trimethylsiloxy ketones and esters. The best result was obtained using Bu4NPF6 as a supporting electrolyte and a Pb cathode in THF. The α-trimethylsiloxy-containing products were transformed to the corresponding α-hydroxy ketones and esters by treatment with TBAF in THF. This method was also effective for the intramolecular reductive coupling of δ- and ε-keto acylimidazoles.
- Kise, Naoki,Agui, Syun,Morimoto, Shinji,Ueda, Nasuo
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p. 9407 - 9410
(2007/10/03)
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- Mg-promoted mixed pinacol coupling
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Mg-promoted reduction of a mixture of aromatic ketones (or imines) and aliphatic carbonyl compounds in N,N-dimethylformamide (DMF) brought about unique mixed pinacol type of cross coupling to give unsymmetrical vicinal diols (or amino alcohols) or α-hydroxyketones in good to moderate yields. The reaction may be initiated by electron transfer from magnesium metal to an aromatic carbonyl compound possessing a less negative reduction potential. The difference of reduction potential between aromatic ketones (or imines) and aliphatic carbonyl compounds was found to be one of the important key factors in this selective cross coupling.
- Maekawa, Hirofumi,Yamamoto, Yoshimasa,Shimada, Hisashi,Yonemura, Kazuaki,Nishiguchi, Ikuzo
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p. 3869 - 3872
(2007/10/03)
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- Asymmetric catalysis. Part 153: Metal-catalysed enantioselective α-ketol rearrangement
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Promoted by catalytic amounts of Ni complexes tertiary α-hydroxyketones 1a, 3a-5a undergo rearrangement, forming chiral isomers 1b, 3b-5b. The best enantioselection was obtained with the model system 1-benzoylcyclopentanol 4a/2-hydroxy-2-phenylcyclohexanone 4b. In a ligand screening 2-[4-(S)-tert-butyloxazolin-2-yl]pyridine gave the highest enantiomeric excess of 46% (S)-4b. The analogous isomerisation reactions of α-hydroxyimines 6a, 7a forming chiral α-aminoketones 6b, 7b were established.
- Brunner, Henri,Kagan, Henri B.,Kreutzer, Georg
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p. 2177 - 2187
(2007/10/03)
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- Asymmetric catalysis. Part 137: Nickel catalysed enantioselective α-ketol rearrangement of 1-benzoylcycloalkanols
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Using catalytic amounts of Ni complexes the tertiary α-hydroxyketones 1-benzoylcyclobutanol 1 and 1-benzoylcyclopentanol 3 undergo α-ketol rearrangement. The use of the chiral ligand 2,6-bis[(4S)-isopropyl-2-oxazolin-2-yl]pyridine gave an enantiomeric exc
- Brunner, Henri,Kagan, Henri B.,Kreutzer, Georg
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p. 497 - 499
(2007/10/03)
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- Oxidative Cleavage of vic-Diols Using Copper(II) Bromide-Lithium t-Butoxide: A New Route to Unsymmetrical 1,5- and 1,6-Diketones
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Unsymmetrical 1,6-diketones were obtained by the copper(II) bromide-lithium t-butoxide oxidation of 1,2-disubstituted 1,2-cyclohexanediols. The diols were easily prepared by the addition of Grignard reagents to 2-trimethylsiloxy-2-cyelohexenone followed by the hydrolysis and treatment of the resulting 2-hydroxycyclohexanones with the second Grignard reagents. Similarly, 1,5-Diketones were obtained using 2-trimethylsiloxy-2-cyclopentenone as a starting material.
- Fujiwara, Tooru,Tsuruta, Yumiko,Arizono, Ko-Ichi,Takeda, Takeshi
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p. 962 - 964
(2007/10/03)
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- Preparation of cyclic α-hydroxy ketones from δ- and ε-keto acids induced by the generation of a novel acyl anion equivalent from the carboxyl group
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An improved method for the transformation of keto acids into cyclic α-hydroxy ketones, induced by the electrochemical generation of a novel acyl anion equivalent from the carboxyl group, has been developed. Both five- and six-membered rings were construct
- Maeda, Hatsuo,Ashie, Haruka,Maki, Toshihide,Ohmori, Hidenobu
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p. 1729 - 1733
(2007/10/03)
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- Preparation and Enantiomer Recognition Behaviour of Crown Ethers containing cis-1-Phenylcyclohexane-1,2-diol and trans-1,2-Diphenylcyclohexane-1,2-diol as a Chiral Subunit
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Pig liver esterase-mediated hydrolysis of (+/-)-cis-2-acetoxy-1-phenylcyclohexanol 5 gave (+)-cis-1-phenylcyclohexane-1,2-diol 4 of high optical purity, from which (-)-trans-1,2-diphenylcyclohexane-1,2-diol 8 has been prepared.Using these diols (+)-4 and
- Naemura, Koichiro,Miyabe, Hajime,Shingai, Yasuhiro,Tobe, Yoshito
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p. 1073 - 1078
(2007/10/02)
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- Synthesis and Enantiomer Recognition of Crown Ethers containing Cyclohexane-1,2-diol Derivatives as the Chiral Centre and Enzymatic Resolution of the Chiral Subunits
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The cyclohexane-1,2-diol derivatives 1 and 4 of high optical purity have been prepared by enantioselective hydrolysis of their acetates (+/-)-2 and (+/-)-5 using pig liver esterase.The enantiomer recognition behaviour of the chiral crown ethers 11, 14, 15
- Naemura, Koichiro,Miyabe, Hajime,Shingai, Yasuhiro
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p. 957 - 959
(2007/10/02)
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- α-Oxidation of ketones using n-cation radicals
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Six-membered ring ketones and acyclic ketones were oxidized by stable triarylamminium radical cations in moist acetonitrile at room temperature in the presence of a base to α-hydroxy ketones in good yield. Five-membered ring ketones gave the corresponding αβ-unsaturated compounds.
- Schulz, Manfred,Kluge, Ralph,Sivilai, Li,Kamm, Birgit
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p. 2371 - 2380
(2007/10/02)
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- Process for the preparation of α-hdroxyketones
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A process for the preparation of α-hydroxyketones STR1 having a high purity in a good yield from a compound STR2 by rearrangement reaction in aqueous alkaline solution, where R1 and R3 each represent an alkyl, alkenyl or aryl group,
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- Asymmetric Synthesis Using Chiral Acetals: Studies on the Nucleophilic Addition of Organometallics to Chiral α-Keto Acetals in Cyclic Systems
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Four chiral cyclic α-keto acetals (3a-d) were prepared through transacetalization of the α-hydroxydimethyl acetals with (-)-(2S,3S)-1,4-dimethoxy-2,3-butanediol or (-)-(2R,3R)-2,3-butanediol and reacted with organometallic reagents (Grignard reagents and organolithium reagents).The reactions of the α-keto acetals (3a, 3b) derived from 1 and (-)-(2S,3S)-1,4-dimethoxy-2,3-butanediol with Grignard reagents proceeded in a highly diastereoselective manner.Keywords-Asymmetric synthesis; diastereoselective nucleophilic addition; chiral cyclic α-keto-acetal; (-)-(2S,3S)-1,4-dimethoxy-2,3-butanediol; (-)-(2R,3R)-2,3-butanediol; Grignard reagent; organolithium reagent
- Tamura, Yasumitsu,Annoura, Hirokazu,Kondo, Hiroshi,Fuji, Masahiro,Yoshida, Takayuki,Fujioka, Hiromichi
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p. 2305 - 2313
(2007/10/02)
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- Diels-Alder Approach to Bicyclic α-Hydroxy Ketones. Facile Ketol Rearrangements of Strained α-Hydroxy Ketones
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The trimethylsiloxy-substituted dienophiles 1-benzoyl-1-(trimethylsiloxy)ethylene, 6, 1-carbomethoxy-1-(trimethylsiloxy)ethylene, 12, and 1-acetyl-1-(trimethylsiloxy)ethylene, 4, all reacted with cyclopentadiene to give adducts in which the carbonyl containing substituent of the major product occupied the exo position, in violation of the Alder rule.Desilylation of the Diels-Alder adducts of cyclopentadiene with 4 and 6 led to ring-expanded ketol rearrangement products on silica gel chromatography.This facile rearrangement was attributed to relief of strain in the star ting α-hydroxy ketone.Equilibration studies showed that in the rearranged 2-hydroxy-2-substituted bicyclooctan-3-one systems 24 and 30, the more stable isomer is the one in which the phenyl or methyl substituent is in the axial position.The presence of a strong intramolecular hydrogen bond of the equatorial hydroxyl group with the carbonyl group accounts for the greater stability of 24 and 30.Acetolysis of endo-2-benzoyl-exo-2-norbornyl mesylate, 2, occurred readily, giving mainly the rearranged product of internal return, 1-benzoyl-exo-norbornyl mesylate, 38.The high reactivity of 2 relative to the endo analogue and the α-H analogue was attributed to some transition-state carbonyl conjugation with the incipient α-keto cation center as well as possible neighboring ?-participation and/or steric rate enhancement.
- Creary, Xavier,Inocencio, Pamela A.,Underiner, Ted L.,Kostromin, Ray
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p. 1932 - 1938
(2007/10/02)
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