- Stereoselective Alkylation of Chiral Titanium(IV) Enolates with tert-Butyl Peresters
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Here, we present a new stereoselective alkylation of titanium(IV) enolates of chiral N-acyl oxazolidinones with tert-butyl peresters from Cα-branched aliphatic carboxylic acids, which proceeds through the decarboxylation of the peresters and the subsequent formation of alkyl radicals to produce the alkylated adducts with an excellent diastereoselectivity. Theoretical calculations account for the observed reactivity and the outstanding stereocontrol. Importantly, the resultant compounds can be easily converted into ligands for asymmetric and catalytic transformations.
- Pérez-Palau, Marina,Sanosa, Nil,Romea, Pedro,Urpí, Fèlix,López, Rosa,Gómez-Bengoa, Enrique,Font-Bardia, Mercè
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supporting information
p. 8852 - 8856
(2021/11/17)
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- Synthesis of enantioenriched α-chiral bicyclo[1.1.1]pentanes
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Bicyclo[1.1.1]pentanes (BCPs), useful surrogates for para-substituted arenes, alkynes, and tert-butyl groups in medicinal chemistry, are challenging to prepare when featuring stereogenic centers adjacent to the BCP. We report the development of an efficie
- Wong, Marie L. J.,Mousseau, James J.,Mansfield, Steven J.,Anderson, Edward A.
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supporting information
p. 2408 - 2411
(2019/03/26)
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- Asymmetric Total Synthesis and Evaluation of Antitumor Activity of Ophiorrhisine A and Its Derivatives
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The first asymmetric total synthesis of ophiorrhisine A (1), a new cyclic tetrapeptide isolated from Ophiorrhiza nutans, was accomplished via an intramolecular aromatic nucleophilic substitution reaction (IMSNAr) of a linear tripeptide to construct a 14-membered paracyclophane ring, resulting in confirmation of its structure and absolute configuration. The structure-activity relationship study of 1 and its derivatives demonstrated that some derivatives possessed cytotoxicity toward human cancer cell lines A549, HT29, and HCT116.
- Onozawa, Tadayoshi,Kitajima, Mariko,Kogure, Noriyuki,Takayama, Hiromitsu
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p. 15312 - 15322
(2019/01/03)
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- Stereoselective Oxidation of Titanium(IV) Enolates with Oxygen
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A novel approach to synthesize enantiomerically pure α-hydroxy carboxylic derivatives is reported. A highly stereoselective oxidation of titanium(IV) enolates from chiral N -acyloxazolidinones is performed with oxygen under simple experimental conditions
- Gómez-Palomino, Alejandro,Romea, Pedro,Urpí, Fèlix
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p. 2721 - 2726
(2018/06/08)
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- Stereoselective aminoxylation of biradical titanium enolates with TEMPO
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A highly efficient and straightforward aminoxylation of titanium(IV) enolates from (S)-N-acyl-4-benzyl-5,5-dimethyl-1,3-oxazolidin-2-ones with TEMPO has been developed. A wide array of functional groups on the acyl moiety, including alkyl and aryl substituents, olefins, esters, or α-cyclopropyl, as well as α-trifluoromethyl groups, are well tolerated. This transformation can therefore produce the α-aminoxylated adducts in excellent yields with high diastereomeric ratios (d.r.). In turn, parallel additions to the α,β-unsaturated N-acyl counterparts give the corresponding γ-adducts with complete regioselectivity in moderate to good yields. Removal of the piperidinyl moiety or the chiral auxiliary converts the resultant adducts into enantiomerically pure α-hydroxy carboxyl derivatives, alcohols, or esters in high yields under mild conditions. Finally, a new mechanistic model based on the biradical character of the titanium(IV) enolates has been proposed.
- Gomez-Palomino, Alejandro,Pellicena, Miquel,Romo, Juan Manuel,Sola, Ricard,Romea, Pedro,Urpi, Felix,Font-Bardia, Merce
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supporting information
p. 10153 - 10159
(2014/08/18)
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- Asymmetric radical addition of TEMPO to titanium enolates
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A mild method for a-hydroxylation of N-acyl oxazolidinones by asymmetric radical addition of the 2,2,6,6-tetramethylpiperidine N-oxy (TEMPO) radical to titanium enolates was developed. The high diastereoselectivity and broad scope of the reaction show synthetic utility for the a-hydroxylation of substrates that are not tolerant to strongly basic conditions.
- Mabe, Phillip J.,Zakarian, Armen
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supporting information
p. 516 - 519
(2014/04/03)
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- A simple method for asymmetric trifluoromethylation of N-acyl oxazolidinones via Ru-catalyzed radical addition to zirconium enolates
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A Ru-catalyzed direct thermal trifluoromethylation and perfluoroalkylation of N-acyloxazolidinones has been developed. The reaction is experimentally simple and requires inexpensive reagents while providing good yields of products with good levels of stereocontrol. Preliminary studies have shown notable compatibility with functional groups, aromatics, and certain heteroaromatic substituents. The described method provides a useful alternative for the synthesis of fluorinated materials in an experimentally convenient manner.
- Herrmann, Aaron T.,Smith, Lindsay L.,Zakarian, Armen
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p. 6976 - 6979
(2012/06/15)
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- Dihydroxylation-based approach for the asymmetric syntheses of hydroxy-γ-butyrolactones
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A method of preparing enantiopure hydroxy-γ-butyrolactones containing multiple contiguous stereocenters in high yield with good diastereoselectivity has been developed. Osmium tetroxide mediated dihydroxylation of a range of β-alkenyl-β-hydroxy-N-acyloxazolidin-2-ones results in formation of triols that undergo spontaneous intramolecular 5-exo-trig cyclization reactions to provide hydroxy-γ-butyrolactones. The stereochemistry of these hydroxy-γ-butyrolactones has been established using NOE spectroscopy, which revealed that 1-substituted, 1,1-disubstituted, (E)-1,2-disubstituted, (Z)-1,2-disubstituted, and 1,1,2-trisubstituted alkenes undergo dihydroxylation with anti-diastereoselectivity, while 1,2,2-trisubstituted systems afford syn-diastereoisomers. The synthetic utility of this methodology has been demonstrated for the asymmetric synthesis of the natural product 2-deoxy-d-ribonolactone. Published 2011 by the American Chemical Society.
- Peed, Jennifer,Davies, Iwan R.,Peacock, Lucy R.,Taylor, James E.,Kociok-Koehn, Gabriele,Bull, Steven D.
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p. 543 - 555
(2012/02/04)
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- Catalytic enantioselective Steglich rearrangements using chiral N-heterocyclic carbenes
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The evaluation of a range of enantiomerically pure NHCs, prepared in situ from imidazolinium or triazolium salt precatalysts, to promote the catalytic enantioselective Steglich rearrangement of oxazolyl carbonates to their C-carboxyazlactones, is reported. Modest levels of enantioselectivity (up to 66% ee) are observed using oxazolidinone derived NHCs.
- Campbell, Craig D.,Concellon, Carmen,Smith, Andrew D.
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p. 797 - 811
(2011/08/06)
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- Enantioselective preparation of P-chiral phosphine oxides
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A highly efficient chiral auxiliary-based strategy for the asymmetric synthesis of P-chiral phosphine oxides in >98:2 er has been developed. The methodology involves the highly stereoselective formation of P-chiral oxazolidinones that then undergo displacement with a variety of Grignard reagents to prepare the desired phosphine oxides.
- Adams, Harry,Collins, Rebecca C.,Jones, Simon,Warner, Christopher J. A.
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p. 6576 - 6579
(2012/01/15)
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- Synthesis of azide-alkyne fragments for 'click' chemical applications. formation of chiral 1,4-disubstituted-(β-alkyl) γ- 1,2,3-triazole scaffolds from orthogonally protected chiral β-alkyl-trialkylsilyl γ- Pentynyl azides and chiral β-alkyl γ- Pentynyl-alcohols
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A library of chiral γ-pentynyl alcohols and γ-pentynyl azides was made using the SuperQuat auxiliary. Coupling of the free alkynes with the azides by Huisgen 1,3-dipolar cycloaddition provided chiral oligomeric 1,4-disubstituted-1,2,3-triazoles as possible peptidomimetic compounds.
- Montagnat, Oliver D.,Lessene, Guillaume,Hughes, Andrew B.
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body text
p. 1541 - 1549
(2011/09/16)
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- A temporary stereocentre approach for the asymmetric synthesis of chiral cyclopropane-carboxaldehydes
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A novel way of combining chiral auxiliaries and substrate directable reactions is described that employs a three-step sequence of aldol/cyclopropanation/retro-aldol reactions for the asymmetric synthesis of enantiopure cyclopropane-carboxaldehydes. In the first step, reaction of the boron enolate of (S)-N-propionyl-5,5-dimethyl-oxazolidin-2-one with a series of α,β-unsaturated aldehydes affords their corresponding syn-aldol products in high de. In the second step, directed cyclopropanation of the alkene functionalities of these syn-aldols occurs under the stereodirecting effect of their 'temporary'β-hydroxyl stereocentres to give a series of cyclopropyl-aldols in high de. Finally, retro-aldol cleavage of the lithium alkoxide of these cyclopropyl-aldols results in destruction of their temporary β-hydroxy stereocentres to afford the parent chiral auxiliary and chiral cyclopropane-carboxaldehydes in >95% ee. The potential of this methodology has been demonstrated for the asymmetric synthesis of the cyclopropane containing natural product cascarillic acid in good yield.
- Cheeseman, Matt,Davies, Iwan R.,Axe, Phil,Johnson, Andrew L.,Bull, Steven D.
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scheme or table
p. 3537 - 3548
(2010/01/06)
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- Efficient asymmetrie synthesis of chiral hydroxy-y-butyrolactones
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Treatment of β-vinyl-β-hydroxy-N-acyloxazolidin-2-ones with VO(acac)2 and tert-butyl hydroperoxide results In formation of unstable epoxides that are ring-opened by intramolecular nucleophilic attack of their exocyclic carbonyl fragments to aff
- Davies, Iwan R.,Cheeseman, Matt,Green, Rachel,Mahon, Mary F.,Merritt, Andrew,Bull, Steven D.
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scheme or table
p. 2896 - 2899
(2009/12/06)
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- Stereocontrolled total synthesis of (-)-kainic acid
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A stereocontrolled total synthesis of (-)-kainic acid is described. A fully functionalized trisubstituted pyrrolidine ring was constructed by ring-closing metathesis of an acrylate derivative followed by an intramolecular Michael addition of the resultant
- Sakaguchi, Hiroshi,Tokuyama, Hidetoshi,Fukuyama, Tohru
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p. 1635 - 1638
(2008/02/02)
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- A SuperQuat glycolate aldol approach to the asymmetric synthesis of hexose monosaccharides
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A stereoselective two-carbon homologation protocol has been developed and applied to the asymmetric synthesis of the hexose monosaccharides D-galactose, D-fucose, D-idose, D-6-deoxyidose, D-talose and D-6-deoxytalose.
- Davies, Stephen G.,Nicholson, Rebecca L.,Smith, Andrew D.
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p. 348 - 359
(2007/10/03)
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- SuperQuat N-acyl-5,5-dimethyloxazolidin-2-ones for the asymmetric synthesis of α-alkyl and β-alkyl aldehydes
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The proclivity of α-branched N-2′-benzyl-3′-phenylpropionyl derivatives of (S)-4-benzyl-5,5-dimethyl-, (S)-4-phenyl-5,5-dimethyl-, (S)-4-isopropyl-5,5-dimethyl-, (S)-4-benzyl- and (S)-4-benzyl-5,5-diphenyl-oxazolidin-2-ones to generate directly 2-benzyl-3-phenylpropionaldehyde upon hydride reduction with DIBAL is investigated. The (S)-4-benzyl-5,5-dimethyl-derivative proved optimal for inhibition of endocyclic nucleophilic attack, giving 2-benzyl-3-phenylpropionaldehyde in good yield upon reduction. Application of this methodology for the asymmetric synthesis of chiral aldehydes via diastereoselective enolate alkylation of a range of (S)-N-acyl-4-benzyl-5,5-dimethyloxazolidin-2-ones to afford an array of α-substituted-N-acyl-5,5-dimethyloxazolidin-2-ones (85-94% de) and subsequent reduction with DIBAL afforded directly non-racemic α-substituted aldehydes without loss of stereochemical integrity (87-94% ee). The extension of this protocol for the asymmetric synthesis of β-substituted aldehydes is demonstrated, via the diastereoselective conjugate addition of a range of organocuprates to (S)-N-acyl-4-phenyl-5,5-dimethyloxazolidin-2-ones which proceeds with high diastereoselectivity (generally >95% de). Reduction of the conjugate addition products with DIBAL gives non-racemic β-substituted aldehydes in high yields and in high ee (generally >95% ee). This methodology is exemplified by the asymmetric synthesis of (R)-3-isopropenylhept-6-enal, which has previously been used in the synthesis of (3Z,6R)-3-methyl-6-isopropenyl-3,9-decadien-1-yl acetate, a component of the sex pheromones of the California red scale.
- Bull, Steven D.,Davies, Stephen G.,Nicholson, Rebecca L.,Sanganee, Hitesh J.,Smith, Andrew D.
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p. 2886 - 2899
(2007/10/03)
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- SuperQuat, (S)-4-benzyl-5,5-dimethyl-oxazolidin-2-one for the asymmetric synthesis of α-substituted-aldehydes
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Reduction of α-substituted-(S)-N-acyl-4-benzyl-5,5-dimethyl-oxazolidin-2-ones with DIBAL-H in CH2Cl2 affords α-substituted aldehydes with no loss of stereochemical integrity at their α-centre. Copyright (C) 2000 Elsevier Science Ltd.
- Bull, Steven D.,Davies, Stephen G.,Nicholson, Rebecca L.,Sanganee, Hitesh J.,Smith, Andrew D.
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p. 3475 - 3479
(2007/10/03)
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- N-carbamylamino alcohols as the precursors of oxazolidinones via nitrosation-deamination reaction
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Oxazolidinones were effectively prepared from N-carbamylamino alcohols by treatment with nitrous acid, via N-nitroso compound as the intermediate. A new route to (R)-4-benzyloxazolidinone was developed starting from DL- phenylalanine, utilizing D-hydantoinase-catalyzed enantioselective hydrolysis of 5-benzylhydantoin under the dynamic kinetic resolution conditions, and the subsequent reduction to the precursor for the above-mentioned cyclization reaction, by taking advantage of the intermediates bearing an N-carbamylamino functionality.
- Suzuki, Masumi,Yamazaki, Takahiro,Ohta, Hiromichi,Shima, Kyoko,Ohi, Katsuhide,Nishiyama, Shigeru,Sugai, Takeshi
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p. 189 - 192
(2007/10/03)
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- Total synthesis of (-)-epothilone A
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The total synthesis of (-)-epothilone A by a convergent route is reported. The synthesis of the required key intermediates has been improved with respect to stereoselectivity and availability. The access to ethyl ketone 2 has been significantly improved b
- Schinzer, Dieter,Bauer, Armin,Boehm, Oliver M.,Limberg, Anja,Cordes, Martin
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p. 2483 - 2491
(2007/10/03)
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- The 'SuperQuat' (R)-4-phenyl-5,5-dimethyl oxazolidin-2-one as an effective chiral auxiliary for conjugate additions: Asymmetric synthesis of (-)-aplysillamide B.
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(R)-4-Phenyl-5,5-dimethyl-oxazolidin-2-one, readily available from D- phenylglycine, is shown to be an effective chiral auxiliary for stereoselective conjugate additions to attached α,β-unsaturated N-acyl moieties. Its utility is demonstrated by the asymmetric synthesis of the antifungal, antibacterial (-)-Aplysillamide B.
- Davies, Stephen G.,Sanganee, Hitesh J.,Szolcsanyi, Peter
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p. 3337 - 3354
(2007/10/03)
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- Chiral auxiliaries
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This invention relates to novel compounds of general formula (I): STR1 wherein the two R1 groups are identical lower alkyl groups or together form a lower alkylene group; R2 and R3 are both different and are selected from hydrogen atoms or organic groups; X and X', which may be the same or different, are selected from O, S and NR, where R represents an organic group; and the asterisk denotes that the configurations of R2 and R3 are such that the compound (I) is in substantially enantiomerically pure 4R- or 4S-form. The compounds are useful chiral auxiliaries to which a wide range of, for example, acyl groups containing prochiral centers may be readily and reversibly coupled to the 3-position amino group.
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- A practical procedure for the multigram synthesis of the SuperQuat chiral auxiliaries
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An efficient and simple synthesis of oxazolidin-2-one SuperQuat chiral auxiliaries is described which provides rapid access to multigram quantities of the auxiliaries.
- Bull, Steven D.,Davies, Stephen G.,Jones, Simon,Polywka, Mario E. C.,Shyam Prasad,Sanganee, Hitesh J.
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p. 519 - 521
(2007/10/03)
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- 4-Substituted-5,5-Dimethyl Oxazolidin-2-ones as Effective Chiral Auxiliaries for Enolate Alkylations and Michael Additions
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4-(Methyl, phenyl, benzyl, and i-propyl)-5,5-dimethyl-oxazolidin-2-ones, readily available from α-amino acids, are shown to be effective chiral auxiliaries for stereoselective enolate alkylations and conjugate additions of attached N-acyl moieties.
- Davies, Stephen G.,Sanganee, Hitesh J.
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p. 671 - 674
(2007/10/02)
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