- N-(chloromethyloxycarbonyl)pyrrolidine as a source of the HOCH2- synthon
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The reaction of N-(chloromethyloxycarbonyl)pyrrolidine (1) with lithium powder and a catalytic amount of DTBB (2.5 mol %) in the presence of different electrophiles [Me3SiCl, Bu(i)CHO, Bu(t)CHO, PhCHO, Et2CO, (CH2)5CO, PhCOMe, Ph2CO] in THF at -78°C leads, after hydrolysis with water, to the expected functionalised carbamates 2. Deprotection of the acetophenone derivative 2g with DIBALH at THF reflux yields, after hydrolysis, the corresponding 1,2-diol 3g.
- Guijarro, Albert,Yus, Miguel
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Read Online
- SN2 Reactions at Tertiary Carbon Centers in Epoxides
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Described herein is a novel concept for SN2 reactions at tertiary carbon centers in epoxides without activation of the leaving group. Quantum chemical calculations show why SN2 reactions at tertiary carbon centers are proceeding in these systems. The reaction allows flexible synthesis of 1,3-diol building blocks for natural product synthesis with excellent control of the relative and absolute configurations.
- Zhang, Yong-Qiang,Poppel, Christina,Panfilova, Anastasia,Bohle, Fabian,Grimme, Stefan,Gans?uer, Andreas
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supporting information
p. 9719 - 9722
(2017/08/08)
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- Selective transition-metal-free vicinal cis-dihydroxylation of saturated hydrocarbons
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A transition-metal-free cis-dihydroxylation of saturated hydrocarbons under ambient reaction conditions has been developed. The described approach allows a direct and selective synthesis of vicinal diols. The new reaction thereby proceeds via radical iodination and a sequence of oxidation steps. A broad scope of one-pot dual C(sp3)-H bond functionalization for the selective synthesis of vicinal syn-diols was demonstrated.
- Bering, Luis,Antonchick, Andrey P.
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p. 452 - 457
(2016/12/30)
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- Homogeneous and heterogeneous photoredoxcatalyzed hydroxymethylation of ketones and keto esters: Catalyst screening, chemoselectivity and dilution effects
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The homogeneous titanium- and dye-catalyzed as well as the heterogeneous semiconductor particle-catalyzed photohydroxymethylation of ketones by methanol were investigated in order to evaluate the most active photocatalyst system. Dialkoxytitanium dichlorides are the most efficient species for chemoselective hydroxymethylation of acetophenone as well as other aromatic and aliphatic ketones. Pinacol coupling is the dominant process for semiconductor catalysis and ketone reduction dominates the Ti(OiPr)4/methanol or isopropanol systems. Application of dilution effects on the TiO2 catalysis leads to an increase in hydroxymethylation at the expense of the pinacol coupling.
- Griesbeck, Axel G.,Reckenthaeler, Melissa
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supporting information
p. 1143 - 1150
(2014/06/09)
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- Mild deprotection of methylene acetals in combination with trimethylsilyl triflate-2,2′-bipyridyl
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The facile deprotection of methylene acetal protection of diols under mild conditions is established. The combination of trimethylsilyl triflate (TMSOTf) and 2,2′-bipyridyl followed by a weakly acidic hydrolysis was effective and the substrates having acid sensitive functional groups can be tolerated under the stated conditions. The selective deprotection between methylene acetal and benzophenone ketal was achieved.
- Fujioka, Hiromichi,Senami, Kento,Kubo, Ozora,Yahata, Kenzo,Minamitsuji, Yutaka,Maegawa, Tomohiro
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experimental part
p. 426 - 428
(2011/02/26)
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- Dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: Mechanistic comparators for artemisinin in the context of reaction pathways with iron(II)
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Single electron reduction of the 1,2,4-trioxane heterocycle of artemisinin (1) forms primary and secondary carbon-centered radicals. The complex structure of 1 does not lend itself to a satisfactory dissection of the electronic and steric effects that influence the formation and subsequent reaction of these carbon-centered free radicals. To help demarcate these effects, we characterized the reactions of achiral dispiro-1,2,4-trioxolane 4 and dispiro-1,2,4-trioxanes 5-7 with ferrous bromide and 4-oxo-TEMPO. Our results suggest a small preference for attack of Fe(II) on the nonketal peroxide oxygen atom of 1. For 4, but not for 5 and 6, there was a strong preference for attack of Fe(II) on the less hindered peroxide bond oxygen atom. The steric hindrance afforded by a spiroadamantane in a five-membered trioxolane is evidently much greater than that for a corresponding six-membered trioxane. Unlike 1, 5-7 fragment by entropically favored β-scission pathways forming relatively stable α-oxa carbon-centered radicals. These data suggest that formation of either primary or secondary carbon-centered radicals is a necessary but insufficient criterion for antimalarial activity of 1 and synthetic peroxides.
- Tang, Yuanqing,Dong, Yuxiang,Wang, Xiaofang,Sriraghavan, Kamaraj,Wood, James K.,Vennerstrom, Jonathan L.
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p. 5103 - 5110
(2007/10/03)
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- 2,3,5-TRISUBSTITUTED PYRIDINES AS INHIBITORS OF CYCLOOXYGENASE-2
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The invention encompasses the novel compound of Formula (I) as well as a method of treating cyclooxygenase-2 mediated diseases comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound of Formula (I). The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula (I).
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- Efficient o-trimethylsilylation of alcohols and phenols with trimethylsilyl azide catalyzed by tetrabutylammonium bromide under neat conditions
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A very efficient procedure for the trimethylsilylation of a wide variety of alcohols, including primary, allylic, benzylic, secondary, hindered secondary, tertiary, and phenols is reported. The reactions were carried out under neat conditions with trimethylsilyl azide (TMSN3) and, when necessary, in the presence of a catalytic amount (20 mol %) of tetrabutylammonium bromide (TBABr) at 30 or 70 °C. Under catalytic conditions, the yields of the corresponding trimethylsilyl ethers were greater than 91%. This procedure also allows the selective protection of primary and secondary alcohols in the presence of tertiary ones.
- Amantini,Fringuelli,Pizzo,Vaccaro
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p. 6734 - 6737
(2007/10/03)
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- Pyridyl group assisted deprotonation of a methyl group on silicon: Complex induced proximity effect and novel hydroxymethylation
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A novel methodology for the deprotonation of a methyl group on silicon has been developed. This newly developed α-lithiation protocol is based on the intramolecular pyridyl group coordination to stabilize the α-silyl carbanion together with the inherent silicon α effect. It was found that the deprotonation (t-BuLi/Et2O/-78 °C) occurs with 2-pyridyltrimethylsilane but not with other related silanes such as phenyltrimethylsilane, 3-pyridyltrimethylsilane, and 4-pyridyltrimethylsilane. It seems that this deprotonation proceeded through the agency of the complex-induced proximity effect (CIPE) of a 2-pyridyl group on silicon. 1H NMR analysis of (2-pyridyldimethylsilyl)methyllithium revealed the intramolecular coordination of a pyridyl group to lithium. (2-Pyridyldimethylsilyl)-methyllithium was found to react with chlorosilanes, hydrosilanes, chlorostannanes, bromine, iodine, organic bromides, aldehydes, and ketones in good to excellent yields. The resultant adducts were further oxidized with H2O2/KF to give the corresponding alcohols in excellent yields. Thus, this two-step transformation provides an efficient method for the nucleophilic hydroxymethylation.
- Itami,Kamei,Mitsudo,Nokami,Yoshida
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p. 3970 - 3976
(2007/10/03)
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- Tri-n-butyl[2-(trimethylsilyl)-ethoxymethoxymethyl]stannane: A convenient hydroxymethyl anion equivalent
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Tri-n-butyl[2-(trimethylsilyl)-ethoxymethoxymethyl]stannane 3 was used as a protected precursor for a hydroxymethyl anion which was added to various carbonyl and carboxyl electrophiles.
- Fernández-Megía, Eduardo,Ley, Steven V.
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p. 455 - 458
(2007/10/03)
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- N-(α-chloroalkyloxycarbonyl)pyrrolidines as a source of oxygenated d1- reagents
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Reaction of the N-(α-chloroalkyloxycarbonyl)pyrrolidines 1 with lithium powder and a catalytic amount of 4,4'-di-tertbutylbiphenyl (DTBB, 2.5 mol-%) in the presence of different electrophiles [iBuCHO, tBuCHO, PhCHO, Et2CO, (CH2)5CO, PhCOMe, Ph2CO, MeaSiCl], in THF at temperatures ranging between -78 and -60°C leads after hydrolysis with water, to the expected functionalized carbamates 2. Deprotection of compounds 2, derived from carbonyl compounds, with lithium hydroxide in a mixture of ethanol and water at 80°C affords the corresponding 1,2-diols 3.
- Ortiz, Javier,Guijarro, Albert,Yus, Miguel
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p. 3005 - 3012
(2007/10/03)
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- (2-Pyridyldimethylsilyl)methyl lithium as a novel hydroxymethylating reagent
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(2-Pyridyldimethylsilyl)methyl lithium was found to react with organic bromides, aldehydes, ketones, and hydrosilanes in good to excellent yields. The resultant adducts were further oxidized with H2O2/KF to give the corresponding alcohols in excellent yields. Thus, this two-step transformation provides an efficient method for hydroxymethylation.
- Itami, Kenichiro,Mitsudo, Koichi,Yoshida, Jun-ichi
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p. 5537 - 5540
(2007/10/03)
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- Practical hydroxymethylation of aldehydes and ketones via pinacol cross-coupling reactions with paraformaldehyde
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A general and practical method for the direct hydroxymethylation of aldehydes and ketones via pinacol cross-coupling with paraformaldehyde is described. The reaction is promoted by vanadium(II) ions which are conveniently generated from the reduction of VCl3(THF)3 with zinc dust. Excellent yields of terminal diols are obtained and stereoselective coupling is observed with some chiral aldehydes and ketones.
- Park, Jeonghan,Pedersen, Steven F.
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p. 2069 - 2080
(2007/10/02)
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- A DIRECT PREPARATION OF 1,2-DIACETATES FROM ALDEHYDES AND KETONES PROMOTED BY SAMARIUM DIIODIDE
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In a mild reaction mediated by samarium diiodide, ketones and aldehydes have been converted into 1,2-diacetates from commercially available bromomethyl acetate in a single synthetic transformation.
- Enholm, Eric J.,Satici, Hikmet
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p. 2433 - 2436
(2007/10/02)
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- Cyclic Ether Formation in Superacid Media
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The formation of ethers in superacids by interaction of a primary hydroxy group with a carbocation centre has been investigated by a study of cyclisation of suitable substrates, mainly 1-(2-hydroxyethyl)cyclohexanols to give hydrobenzofurans.Cyclisation traps thermodynamically stable ionic species, with rates of reaction dependent upon the size of the ether ring formed.Three- and four-membered ether rings were not formed, five-membered ether rings formed readily, the reaction being comparable in rate with a 1,2-methyl shift.Six-membered rings formed a little less readily and seven-membered rings less readily still, though a yield of 34 percent from a suitable substrate has been recorded.An unexpected feature of the reactions was their stereospecificity; in one case, this is believed to result from a methyl shift concerted with attack of the primary hydroxy group, the reaction proceeding through hindered transition state, in which methyl loss, probably as CH3+, competes with a 1,2-methyl shift.
- Carr, Graham,Whittaker, David
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p. 359 - 366
(2007/10/02)
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- SILAFUNCTIONAL COMPOUNDS IN ORGANIC SYNTHESIS. 27. (ISOPROPOXYDIMETHYLSILYL)METHYL GRIGNARD REAGENT: A NEW NUCLEOPHILIC HYDROXYMETHYLATING AGENT FOR ALDEHYDES AND KETONES
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Nucleophilic hydroxymethylation of aldehydes and ketones has been achieved by the reaction with the (isopropoxydimethylsilyl)methyl Grignard reagent and the subsequent oxidative cleavage of the carbon-silicon bond.
- Tamao, Kohei,Ishida, Neyoshi
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p. 4245 - 4248
(2007/10/02)
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- α-Oxygenation of Aldehydes and Cyclic Ketones by Acylation-Rearrangement of Nitrones
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The reaction of N-tert-butylnitrones (1a-e) of aldehydes and N-methylnitrones (2 and 3) of cyclic ketones with acid chlorides in the presence of triethylamine afforded α-acyloxy imines by rearrangement of N-vinyl-O-acylhydroxylamine intermediates.Hydrolysis of the α-acyloxy imines gave α-acyloxy aldehydes and ketones.The acylation-rearrangement reaction offers a new method for α-oxygenation of carbonyl compounds.
- Cummins, Clark H.,Coates, Robert M.
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p. 2070 - 2076
(2007/10/02)
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- Doubly Metalated Methanol. - Alcohol d1- and d3-Reagents
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The nucleophilic counterpart of the electrophilic hydroxymethylating protonated formaldehyde B is the hypothetical tautomer A, R = H, of methoxide.Experiments are described in which the generation of doubly metalated methanol C (= formaldehyde ketyl dianion) and its use as methanol d1-reagent are attempted.Treatment of stannylated methanol 1 with two equivalents of butyllithium furnishes a pentane-soluble reagent which hydroxymethylates electrophilic centers in moderate yields (umpolung of the formaldehyde a1-reactivity), see eq. (1) and table 3.Attempted isolation, 1H- and 13C-NMR measurements, and careful product analysis of the reaction with benzaldhyde (scheme 1 and table 2) support the view that the new reagent is actually not free lithium lithiomethoxide (2) but a tin derivative, see for instance 9 in eq. (2). - The O-silylated derivative 18 (= A, R = SiMe3) is likewise generated by Sn-Li-transmetallation, but cannot be trapped externally by electrophiles due to rapid Wittig rearrangement (-> 19 -> 20).The readily accessible dilithio derivatives 21a and 23a can be employed as direct propanol and allyl alcohol d3-reagents, respectively.
- Meyer, Norbert,Seebach, Dieter
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p. 1290 - 1303
(2007/10/02)
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- Metal-Catalyzed Organic Photoreactions. Titanium(IV) Chloride Catalyzed Photoreaction of Saturated Ketones with Methanol and Its Application to the Synthesis of Frontalin
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Photoreaction of acyclic and cyclic saturated ketones in methanol in the presence of TiCl4 afforded 1,2-diols as the main products.The effect of the substituents on the stereochemical course of the photoreaction was examined with substituted cyclohexanones.Further, the present reaction was applied for the synthesis of a pheromone, frontalin.
- Sato, Tadashi,Kaneko, Hirokazu,Yamaguchi, Shinichi
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p. 3778 - 3782
(2007/10/02)
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- Studies on the Autoxidation of Some Monocyclic Olefins
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The autoxidations of cyclopentene, cyclohexene, cycloheptene, cyclooctene, cycloocta-1,5-diene, 1-methylcyclopentene, 1-methylcyclohexene, 1-methylcycloheptene, 1-methylcyclooctene, methylene cyclopentene, and methylene cyclohexene with pure oxygen under normal pressure were studied.The epoxides formed were determined gaschromatographically.In most cases also the products of allylic oxidation were analyzed and their structures elucidated after reduction to the corresponding allyl alcohols.The portions of high boiling or polymeric products which could not be detected gaschromatographically and also the real yields of epoxides were determined by balance experiments in the presence of inert internal standards.
- Blau, K.,Mueller, U.,Pritzkow, W.,Schmidt-Renner, W.,Sedshaw, Z.
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p. 915 - 932
(2007/10/02)
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