A Catalytic Enantioselective Electron Transfer Reaction: Titanocene-Catalyzed Enantioselective Formation of Radicals frommeso-Epoxides

Gansäuer, Andreas; Lauterbach, Thorsten; Bluhm, Harald; Noltemeyer, Mathias

doi:10.1002/(sici)1521-3773(19991004)38:19<2909::aid-anie2909>3.0.co;2-y

Cited by 148 publications

(36 citation statements)

References 2 publications

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“…[20] It should be noted that in TS-13 a the steric destabilization is larger than in TS-12 a* since the group containing the secondary hydroxy group (TS-13 a) is bulkier than the n-alkyl chain (TS-12 a*). [20] It should be noted that in TS-13 a the steric destabilization is larger than in TS-12 a* since the group containing the secondary hydroxy group (TS-13 a) is bulkier than the n-alkyl chain (TS-12 a*).…”

Section: Methodsmentioning

confidence: 99%

Synthetic and Computational Evaluation of Regiodivergent Epoxide Opening for Diol and Polyol Synthesis

Gansäuer¹,

Karbaum²,

Schmauch³

et al. 2014

Chemistry An Asian Journal

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In a combined synthetic and computational study, the factors governing the selectivity of the titanocene(III)-catalyzed regiodivergent epoxide opening (REO) with Kagan's complex via electron transfer leading to derivatives of 1,2-, 1,3-, and 1,4-diols were investigated. In this manner, valuable building blocks for the synthesis of 1,3- and 1,4-diols were identified. The computational study provides crucial structural features and energies of the transition states of ring opening that are important for the design of more selective catalysts.

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Section: Methodsmentioning

confidence: 99%

Synthetic and Computational Evaluation of Regiodivergent Epoxide Opening for Diol and Polyol Synthesis

Gansäuer¹,

Karbaum²,

Schmauch³

et al. 2014

Chemistry An Asian Journal

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“…Alternatively, chiral Ti III complexes have been employed to reductively open meso-epoxides to furnish enantiomerically enriched radical anions, which were then trapped with either hydrogen donors or alkenes. [7] The nucleophilic addition of amines to meso-epoxides currently proceeds with only moderate enantioselectity in most cases; [8] the catalytic, enantioselective addition of aliphatic alcohols to meso-epoxides has not been reported at all to date. We report here a novel chiral metal complex capable of catalyzing the alcoholysis as well as aminolysis of meso-epoxides with good yields and in part excellent enantioselectivities.The starting point for our investigations was the observation made by Crotti and co-workers that lanthanide triflates such as Yb(OTf) 3 are effective catalysts for the aminolysis of 1,2-epoxides, presumably because they are able to exert their exceptional Lewis acidity even under protic reaction conditions.…”

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Scandium–Bipyridine‐Catalyzed Enantioselective Addition of Alcohols and Amines to meso‐Epoxides

2004

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“…In contrast, there has been limited success in developing analogous transformations with nucleophilic carbon-centred radicals. While a few examples of metal-catalysed enantioselective radical conjugate additions have been reported [12][13][14][15] , none of these approaches provide for the formation of sterically demanding quaternary carbons. Our herein-reported work was prompted by the desire to address this gap in catalytic enantioselective methodology.…”

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Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals

Murphy

Bastida

Paria

et al. 2016

Nature

375

159

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A central goal of modern organic chemistry is to develop novel catalytic enantioselective carbon-carbon bond-forming strategies for forging quaternary stereogenic centres. While considerable advances have been achieved in the realm of polar reactivity 1 , radical transformations have found very limited application 2 . This is despite the fact that open-shell intermediates are intrinsically primed for connecting structurally congested carbons, as their reactivity is only marginally affected by steric factors 3 . Herein we demonstrate how the combination of photoredox 4 and asymmetric organic catalysis 5 enables enantioselective radical conjugate additions to β,β-disubstituted cyclic enones to set quaternary carbon stereocentres with high fidelity. Key to our success was the design of a chiral organic catalyst, purposely adorned with a redox-active carbazole moiety, which drives the stereoselective interception of photochemically-generated carbon-centred radicals by means of an electron-relay mechanism. We demonstrate the generality of this organocatalytic radical-trapping strategy with two sets of open-shell intermediates, formed through unrelated light-triggered pathways from readily available substrates and photoredox catalysts. To the best of our knowledge, this method represents the first application of iminium ion activation 6 (a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.Organic chemists generally rely on polar reactivity to address the challenge of forging quaternary carbon stereocentres in a catalytic enantioselective fashion 1 . Of the synthetic methods available, metal-catalysed conjugate additions of organometallic nucleophilic species to trisubstituted unsaturated carbonyl substrates have recently emerged as a powerful technology [7][8][9][10][11] (Fig. 1a). These are reliable and stereoselective processes, but they generally require controlled reaction conditions and preformed organometallic reagents 7-10 . In contrast, there has been limited success in developing analogous transformations with nucleophilic carbon-centred radicals. While a few examples of metal-catalysed enantioselective radical conjugate additions have been reported [12][13][14][15] , none of these approaches provide for the formation of sterically demanding quaternary carbons. Our herein-reported work was prompted by the desire to address this gap in catalytic enantioselective methodology.Our initial motivation stems from the notion that, due to the long incipient carbon-carbon bond in the early transition state 16 , additions of radicals to electron-deficient olefins are rather insensitive to steric hindrance 3 . This makes radical reactivity particularly suited to connecting structurally complex carbon fragments while forging quaternary carbons, as testified to by literature synthesis of a natural product facilitated by radical conjugate additions 17 .

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A Catalytic Enantioselective Electron Transfer Reaction: Titanocene-Catalyzed Enantioselective Formation of Radicals frommeso-Epoxides

Abstract: A rationally designed titanium(III) catalyst allows the opening of epoxides with high enantioselectivity. This reaction [Eq. (1)] constitutes the first example of an enantioselective transition metal catalyzed radical reaction that proceeds by electron transfer.

Cited by 148 publications

References 2 publications

Synthetic and Computational Evaluation of Regiodivergent Epoxide Opening for Diol and Polyol Synthesis

Synthetic and Computational Evaluation of Regiodivergent Epoxide Opening for Diol and Polyol Synthesis

Scandium–Bipyridine‐Catalyzed Enantioselective Addition of Alcohols and Amines to meso‐Epoxides

Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals

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