- Stereochemical Effects in the Gas-Phase Pinacol Rearrangement of cis- and trans-1,2-Dimethylcyclopentane-1,2-diol
-
The pinacol rearrangement of cis- and trans-1,2-dimethylcyclopentane-1,2-diol, promoted by the gaseous Broensted acids D3+, CH5+/C2H5+, and t-C4H9+, was studied by mass spectrometric and radiolytic methods.Dehydration of the protonated substrate is rate limiting, and competitive experiments with pinacol, carried out at high pressure (760 torr), showed that the cis rearranges more rapidly than the trans isomer, indicating participation of the migrating methyl group to the leaving water molecule.The results are compared with those concerning the same substrates in solution, where no evidence of anchimeric assistance was found.
- Petris, Giulia de,Giacomello, Pierluigi,Picotti, Tito,Pizzabiocca, Adriano,Renzi, Gabriele,Speranza, Maurizio
-
-
Read Online
- Preparation method of 2, 2-dimethyl cyclopentanone
-
The invention discloses a preparation method of 2, 2-dimethyl cyclopentanone, which comprises the following steps: methylating 2-methoxycarbonyl cyclopentanone to obtain a methylated product 2-methyl-2-methoxycarbonyl cyclopentanone, carrying out keto-carbonyl protection on the methylated product to obtain a protected product 2-methyl-2-methoxycarbonyl cyclopentanone ketal, carrying out ester group reduction on the protection product to obtain an alcohol product 2-hydroxymethyl-2-methyl cyclopentanone ketal, carrying out deprotection on the alcohol product under an acidic condition to obtain a deprotection product 2-hydroxymethyl-2-methyl cyclopentanone, and brominating the deprotection product to obtain 2-bromomethyl-2-methyl cyclopentanone. All raw materials adopted by the method are low in cost and easy to obtain in the market, and reactions in all steps are conventional reactions and easy to implement; the process is simple, mild in reaction condition and easy to operate; the reaction time is short, control is easy, the yield of each step is 90% or above, and industrial large-scale production is easy to achieve.
- -
-
Paragraph 0022
(2021/06/23)
-
- METHOD FOR INTRODUCING SUBSTITUENT INTO alpha,beta-UNSATURATED KETONE AND METHOD FOR SYNTHESIZING PROSTAGLANDIN USING THE SAME
-
The present invention provides a method for introducing substituents into the α-position and the β-position of an α,β-unsaturated ketone, which not only can be used for the synthesis of a prostaglandin by a three-component coupling process, but also enables synthesis of a prostaglandin in a high yield by one-pot operation without requiring the use of a large excess amount of any of the three components required for the synthesis or using a highly toxic heavy metal as a catalyst or a solvent that is highly toxic to living bodies, and a method for synthesizing a prostaglandin using the same technical means. The method for introducing substituents into an α,β-unsaturated ketone according to the present invention is a method for introducing substituents into the carbon at the α-position and the carbon at the β-position of an α,β-unsaturated ketone, including: a first step of mixing alkyllithium and trialkylalkenyl tin in which tin atom binds to the vinyl position of the alkenyl group; a second step of mixing the mixture of the first step and dialkylzinc; a third step of mixing the mixture of the second step and an α,β-unsaturated ketone; and a fourth step of mixing the mixture of the third step and a trifluoromethanesulfonate compound.
- -
-
Paragraph 0044-0046
(2021/11/20)
-
- Organozinc-aided, HMPA-free, stoichiometric three-component coupling for the general synthesis of prostaglandins and stable prostacyclin analogs with biological significance
-
A three-component coupling procedure was developed to construct the entire prostaglandin (PG) skeleton under HMPA-free and stoichiometric conditions via a combination of dimethylzinc-aided conjugate addition of an ω-side-chain vinyllithium with (R)-4-hydroxy-2-cyclopentenone and the direct trapping of the resulting enolate with an α-side-chain propargyl triflate. Dimethylzinc effectively regulated both the conjugate addition and alkynylation reactions. Thus, the method afforded protected 5,6-didehydro-PGE2, a common intermediate for the general synthesis of natural PGs and the stable artificial prostacyclin (PGI2) analog isocarbacyclin in 88% yield. The utility of the method was further applied to the syntheses of novel intermediates, which are useful for the straightforward synthesis of 15R-TIC and 15-deoxy-TIC in 79% and 86% yield, respectively.
- Koyama, Hiroko,Izumiseki, Atsuto,Suzuki, Masaaki
-
p. 1467 - 1470
(2019/05/07)
-
- Regioselective Dialkylations of N-(tert-Butyl)iminocyclopentane via Deprotonating One-Pot Procedures
-
The title compound (1) was chosen as a model for the α/α′-regioselectivity of deprotonation and subsequent alkylation adjacent to the C=N bond. With the bulky base lithium N,N-diisopropylamide (LDA) as a catalyst, the one-pot deprotonation steps can be performed through titration with methyllithium, using gas-volumetric observation of the liberated methane. In the first step with ensuing methylation by iodomethane, the primary product is born at ?40?°C in its metastable (Z) configuration (kinetic control) and may be either isolated or converted in?situ at 30?°C into its thermodynamically favored (E)-isomer via cis to trans stereoinversion at the N-atom. Being slow enough on the laboratory time scale, this stereoinversion process can serve to control the regioselectivity of the second deprotonation/alkylation sequence as follows. The α,α′-products are formed from the intermediate (Z)-imine, whereas α,α-products result from the intermediate (E)-imine; in either case, syn deprotonation (cis to tBu at nitrogen) by LDA is apparently disfavored by the tBu group, so that anti deprotonation becomes obligatory. If a third one-pot deprotonation step is too slow with LDA, it may be performed with the stronger base butyllithium/HMPA which, however, reacts regio-unselectively. Regioselective one-pot, LDA-catalyzed deprotonation with alkylation by oxiranes (alone, or alternatingly with iodomethane) opens a short access to spiro-[2.4]heptan-4-ones.
- Knorr, Rudolf,Neuner, Brigitte
-
-
- SUBSTITUTED HETEROCYCLIC AMINE COMPOUNDS AS CHOLESTRYL ESTER-TRANSFER PROTEIN (CETP) INHIBITORS
-
The present application relates to cycloalkylpyridin-2-amines derivates of formula (I) or stereoisomers thereof or pharmaceutically acceptable salts thereof. The present application also relates to the process for the preparation of compounds of formula (I). The present application further describes the compounds of formulat (I) as cholesteryl ester-transfer protein (CETP) inhibitors. The present application further relates to pharmaceutical compositions comprising compounds of formula (I) or stereoisomers thereof or pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 24; 25
(2013/03/26)
-
- Catalytic asymmetric synthesis of a tertiary benzylic carbon center via phenol-directed alkene hydrogenation
-
An expeditious synthetic approach to chiral phenol 1, a key building block in the preparation of a series of drug candidates, is reported. The strategy includes a cost-effective and readily scalable route to cyclopentanone 3 from isobutyronitrile (10). The sterically hindered and enolizable ketone 3 was subsequently employed in a challenging Grignard addition mediated by LaCl 3?2LiCl. A novel preparation of the lanthanide reagent required for this transformation is described. To complete the process, a highly enantioselective hydrogenation step afforded the target (1). The importance of the phenol group to the success of this asymmetric transformation is discussed.
- Caille, Seb,Crockett, Rich,Ranganathan, Krishnakumar,Wang, Xiang,Woo, Jacqueline C. S.,Walker, Shawn D.
-
experimental part
p. 5198 - 5206
(2011/08/09)
-
- Cyclic ketones, their preparation and their use in the synthesis of amino acids
-
A method is provided for making an enantiomerically pure of the formula: in which R and R′ represent C1?C10 alkyl, C2?C10 alkenyl or C3?C10 cycloalkyl and the wedges signify (S)- or (R)-stereochemistry, the substituents in compound (II) being trans. Conjugate addition is carried out between an organometallic nucleophile that provides a group R as defined above and (R)-4-acetoxycyclopent-2-en-1-one, (S)-4-acetoxycyclopent-2-en-1-one or a similar compound in which acetoxy is replaced by another leaving group to give, e.g. in the case of the acetoxy compound, a trans 3,4-disubstituted addition product of formula III or IV; The acetyl group is eliminated from the addition product to give an (R)- or (S)-4-alkyl or 4-alkenyl cyclopent-2-en-1-one the compound of formula is then to be hydrogenated to give a cyclopentanone of formula (I) or conjugate addition of a second organometallic nucleophile that provides a group R′ as defined above to the compound of the above formula may be carried out to give a trans 3,4-disubstituted addition product of formula (II). One of the above compounds may be converted e.g. via an intermediate (XV)-(XVIII) (in which the substituents R and R′ and the wedges have the meanings indicated above) to a gabapentin analogue of one of the formulae shown below: in which the substituents R and R′ and the wedges also have the meanings indicated above.
- -
-
-
- Cyclic amino acids and derivatives thereof useful as pharmaceutical agents
-
The invention is a novel series of cyclic amino acids which are useful in the treatment of epilepsy, faintness attacks, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, gastrointestinal disorders such as irritable bowel syndrome (IBS), and inflammation, especially arthritis. A pharmaceutical composition containing a compound of the invention as well as methods of preparing the compounds and novel intermediates useful in the preparation of the final compounds are included.
- -
-
-
- Amidino derivatives useful as nitric oxide synthase inhibitors
-
The current invention discloses useful pharmaceutical compositions containing amidino derivative useful as nitric oxide synthase inhibitors.
- -
-
-
- Preparation of cyclic ketones
-
Cyclic ketones, notably cyclopentanone and 2,2-dimethylcyclopentanone, are simply, economically and efficiently prepared, even on an industrial scale, by decarboxylating/cyclizing a dicarboxylic acid, in liquid phase, in the presence of a catalytically effective amount of a metal or compound thereof selected from among boron, aluminum, gallium, indium, thallium, tin, antimony, bismuth, molybdenum, rubidium, cesium and vanadium.
- -
-
-
- Regioselective synthesis of α,α-dialkylcyclopentanones from 1-hydroxycyclobutanecarboxylic acid or from O-protected cyclobutanone cyanohydrin
-
1-(1-Hydroxyalkyl)cyclobutanols 4a-f, readily available either from 1-hydroxycyclobutane carboxylic acid or from O-protected cyclobutanone cyanohydrin, appeared the most suitable precursors for a regioselective synthesis of cyclopentanones α,α- disubstituted with various similar or different alkyl, alkenyl, aryl or cycloalkyl groups. The key steps consist of acid or Grignard reagent induced C4→C5 ring expansions.
- Estieu, Karine,Ollivier, Jean,Salauen, Jacques
-
p. 8075 - 8090
(2007/10/03)
-
- Amidino dervatives useful as nitric oxide synthase inhibitors
-
The current invention discloses useful pharmaceutical compositions containing azepine derivatives useful as nitric oxide synthase inhibitors.
- -
-
-
- Regioselective synthesis of 2,2-dimethylcyclopentanone using 2-pyrrolidone magnesium salt as electrogenerated base
-
An efficient, direct and regioselective preparation of 2,2-dimethylcyclopentanone, via its enolate precursor regioselectively obtained using the 2-pyrrolidone magnesium salt, a base electrogenerated in DME/HMPA, is reported.
- Bonafoux, Dominique,Bordeau, Michel,Biran, Claude,Dunogues, Jacques
-
-
- Highly regioselective alkylation at the more hindered α-site of unsymmetrical ketones by use of their potassium enolates. A comparative study with lithium enolates
-
Alkylation of regioisomeric potassium enolates 4 and 6 obtained from corresponding silyl enol ethers 2 and 3 occurs at the most substituted site affording ketones 8. Alkylation of corresponding lithium enolates 5 and 7 occurs at the expected site affording ketones 8 or 9. As an application the one pot synthesis of spiroketones 13 from silyl enol ethers 12 is described.
- Quesnel, Yannick,Bidois-Sery, Laure,Poirier, Jean-Marie,Duhamel, Lucette
-
p. 413 - 415
(2007/10/03)
-
- Catalytic C-alkylation of ketones
-
Ketones having at least one hydrogen atom or ester group in the α-position with respect to a ketonic carbonyl group thereof, for example cyclopentanone, 2-methylcyclopentanone and other substituted cyclopentanones, are effectively C- or α-alkylated, especially on an industrial scale, by reacting same with an alkylating agent in the presence of a catalytically effective amount of a condensed or uncondensed orthophosphate anion.
- -
-
-
- β-Enolization in α-phenyl-α,α',α'-trimethylcycloalkanones
-
Ring expansion through β-proton abstraction from α-methyl groups has been observed for the α-phenyl-α,α',α'-trimethyl derivatives of cyclopentanone and cyclohexanone upon treatment with t-BuO(1-)/t-BuOH/185 deg C.This contrasts with the lack of rearrangement found for the α,α,α',α'-tetramethyl derivatives but is analogous to the behavior of some α-phenyl acyclic ketones.However, this process is reversible in the cyclic systems, but irreversible in the acyclic cases.For all of these α-phenyl substituted ketones, rearrangement is in competition with Haller-Bauer type cleavage.In the cyclic systems, a minor process was ob served whereby some of the ring-expanded product is reduced to the corresponding secondary alcohol but there was no evidence of rearrangement through γ-enolate formation involving phenyl proton abstraction, which is a minor process in the α-phenyl acyclic systems.
- Sifton, Wendy,Stothers, J. B.,Thomas, Shirley E.
-
p. 1274 - 1280
(2007/10/02)
-
- A Regioselective and Stereospecific Synthesis of Allylsilanes from Secondary Allylic Alcohol Derivatives
-
Primary and secondary allylic acetates and benzoates react with the dimethyl(phenyl)silyl-cuprate reagent to give allylsilanes, provided that the THF in which the cuprate is prepared is diluted with ether before addition of the allylic ester.The reaction is reasonably regioselective in some cases: (i) when the allylic system is more-substituted at one end than the other, as in the reactions 4->5 and 9->10; (ii) when the steric hindrance at one end is neopentyl-like, as in the reactions 15->16; and (iii) when the disubstituted double bond has the Z configuration, as in th e reactions Z-19->E-21 or, better, because the silyl group is becoming attached to the less-sterically hindered end of the allylic system, Z-20->E-22.The regioselectivity is better if a phenyl carbamate is used in place of the ester, and a three-step protocol assembling the mixed cuprate on the leaving group is used, as in the reactions 23->24 and E- or Z-29->E-21, or, best of all, because the silyl group is again becoming attached to the less-sterically hindered end of the allylic system, E- or Z-30->E-22.This sequence works well to move the silyl group onto the more substituted end of an allyl system, but only when the move is from a secondary allylic carbamate to a tertiary allylsilane, as in the reaction 38->39.Allyl(trimethyl)silanes can be made using alkyl- or aryl-cuprates on trimethylsilyl-containing allylic esters and carbamates, as in the reactions 40->41, and 43->44.The reaction of the silyl-cuprate with allylic esters and the three-step sequence with the allylic carbamates are stereochemically complementary, the former being stereospecifically anti and the latter stereospecifically syn.Homochiral allylsilanes can be ma de by these methods with high levels of stereospecificity, as shown by the synthesis of the allylsilanes 54, 58 and 59.
- Fleming, Ian,Higgins, Dick,Lawrence, Nicholas J.,Thomas, Andrew P.
-
p. 3331 - 3350
(2007/10/02)
-
- An Organozinc Aid in Alkylation and Acylation of Lithium Enolates
-
The presence of dimethylzinc in the reaction of lithium enolates and electrophiles effectively suppresses undesired α-proton exchange reaction and enhances the efficiency of enolate alkylation and acylation.
- Morita, Yasushi,Suzuki, Masaaki,Noyori, Ryoji
-
p. 1785 - 1787
(2007/10/02)
-
- CYCLIZATION OF UNSATURATED ALDEHYDES CATALYZED BY (PPh3)2Co(Ph2PCH2CH2PPh2)
-
Catalytic cyclization of γ,δ-unsaturated aldehydes (intramolecular hydroacylation) in the presence of (PPh3)2Co(Ph2PCH2CH2PPh2) gives four-membered and five-membered cycloalkanones.Depending on aldehyde structure the selectivity is 90-97percent at 10-100percent aldehyde conversion.
- Vinogradov, M. G.,Tuzikov, A. B.,Nikishin, G. I.
-
p. 2353 - 2356
(2007/10/02)
-
- Trisubstituted Stannyllithium as a Double Electron Equivalent. Reaction with α,β-Enones
-
β-Stannyl ketones, easily available by the conjugate addition of (trimethylstannyl)lithium to α,β-enones, produced two types of ketones depending upon the substitution pattern by the treatment with titanium(IV) chloride.All the reactions proceeded through an intermediacy of cyclopropanol derivatives.The reaction involving the carbon skeleton rearrangement is promising as a synthetic method.
- Sato, Tadashi,Watanabe, Masami,Watanabe, Toshiyuki,Onoda, Yasuo,Murayama, Eigoro
-
p. 1894 - 1899
(2007/10/02)
-
- Original Syntheses of Carbonyl Compounds and gem-Dihalocyclopropanes from β-Hydroxylalkylselenides
-
β-hydroxyalkylselenides possessing two alkyl substituents on the carbon bearing the selenyl moiety react with dihalocarbenes generated from haloforms and thallous ethoxide or under phase transfer catalysis to produce ring enlarged ketones as the sole product in the first case, as the main product in the second.The reaction takes another course when the dihalocarbenes generated from haloforms and tBuOK or from trihalomethylphenylmercury are employed and leads inter alias to dihalocyclopropanes.
- Krief,A.,Laboureur, J. L.,Dumont, W.
-
p. 1549 - 1552
(2007/10/02)
-
- Branched amides of L-aspartyl-D-amino acid dipeptides
-
Amides of L-aspartyl-D-amino acid dipeptides of the formula STR1 and physiologically acceptable cationic and acid addition salts thereof wherein Ra is CH2 OH or CH2 OCH3 ; R is a branched member selected from the group consisting of fenchyl, diisopropylcarbinyl, d-methyl-t-butylcarbinyl, d-ethyl-t-butylcarbinyl, di-t-butylcarbinyl, 2-methylthio-2,4-dimethylpentan-3-yl, STR2 where at least one of R3, R4, R5, R6 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms, X is O, S, SO, SO2, C=O or CHOH; m is zero or 1-4, n and p are each zero, 1, 2 or 3 where the sum of n+p is not greater than 3 and the sum of the carbon atoms in R3, R4, R5 and R6 is not greater than six, and when both of R3 and R4 or R5 and R6 are alkyl they are methyl or ethyl, STR3 where one of R7, R8, R9 is alkyl having from one to four carbon atoms and the remainder are hydrogen or alkyl having from one to four carbon atoms and the sum of the carbon atoms in R7, R8 and R9 is not greater than six, m and q are the same or different and each have the values previously defined for m; STR4 where each of R12 and R13 are methyl or ethyl, or R12 is hydrogen and R13 is alkyl having from one to four carbon atoms, Z is O or NH and t is 1 or 2, STR5 where W is 1-4, R14 and R16 are each alkyl having from one to four carbon atoms, R15 is H, OH, methyl or ethyl and the sum of the carbon atoms in R14, R15 and R16 is not greater than six and when both of R14 and R15 are alkyl they are methyl or ethyl, and STR6 where R17 and R19 are alkyl having from one to four carbon atoms, R18 and R20 are H or alkyl having one to two carbon atoms, A is OH and B is H, OH or CH3 and taken together A and B are STR7 where the sum of the carbon atoms in R17, R18, R19 and R20 is not greater than six and when both of R17 and R18 or R19 and R20 are alkyl they are methyl or ethyl; said amides are potent sweeteners having advantages over the prior art, edible compositions containing them, methods for their use in edible compositions and novel amide intermediates useful in their production.
- -
-
-
- Nucleophilic substitution of 5,5-dimethyl-2-cyclopentenyl derivatives. Lack of SN2' reaction
-
Treatment of tetramethyl-1,3-cyclobutadienone with two equivalents of allyl oxide anion at 140 deg C yields 2,2-dimethyl-4-pentenoic acid which is cyclized via the acid chloride whith aluminium chloride to 5,5-dimethyl-2-cyclopentenone 4.Reduction of 4 with aluminium hydride provides 5,5-dimethyl-2-cyclopentenol 1-OH which is pyrolyzed to 5,5-dimethyl-1,3-cyclopentadiene in dimethylsulfoxide.Reduction of 4 with tri-t-butoxyaluminium hydride at -70 deg C gives 2,2-dimethylcyclopentanone.The 2,6-dichlorobenzoate ester of 1-OH failed to yield SN2' products under a variety of conditions.The rate constants for solvolysis of the p-nitrobenzoate esters of 1-OH, 2-cyclopentenol and Z-2-methyl-4-hexene-3-ol in 80 percent ethanol at 80 deg C are 20.2, 523, and 0.63 x 1E-6s-1, respectively, and the main products of solvolysis are 5-ethoxy-3,3-dimethylcyclopentene, 3-ethoxycyclopentene, and E-2-ethoxy-5-methyl-3-hexene, respectively.There is steric hindrance to solvatation during ionization of the p-nitrobenzoate of 1-OH.
- Kopecky, Karl R.,Levine, Cyril
-
p. 3273 - 3279
(2007/10/02)
-