Unconventional Biradical Character of Titanium Enolates

Moreira, Ibério de P. R.; Bofill, Josep María; Anglada, Josep M.; Solsona, Joan G.; Nebot, Joaquim; Romea, Pedro; Urpı́, Fèlix

doi:10.1021/ja076625f

Cited by 47 publications

(39 citation statements)

References 14 publications

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“…The stabilization of free radicals is necessary to avoid these problems. Fortunately, the introduction of a transition metal into the radical combination reactions provides an efficient approach to stabilize the radicals and protect them from being quenched by homo-coupling or fragmentation1011121314. Moreover, the interplay between a transition metal and radicals would be able to tune the reactivity of radicals and enable specific radical–radical cross-combination10151617.…”

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Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

Zhu

Bai

et al. 2017

Sci Rep

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Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C–N radical–radical cross-coupling reaction. The concerted coupling pathway, in which a C–N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)–N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)–N species before C–N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)–N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)–N intermediate. The higher activation free energy for N–N radical–radical homo-coupling is attributed to the mismatch of Cu(II)–N species with the nitrogen radical because the electrophilicity for both is strong.

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confidence: 99%

Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

Zhu

Bai

et al. 2017

Sci Rep

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“…11 Although encouraging results were obtained with silyl ketene acetals (~50% yields, ds 3:1), the recent characterization of valence tautomerism in titanium enolates provided a conceptual foundation for the development of a direct radical chloroalkylation of N -acyl oxazolidinones. 12,13…”

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Valence Tautomerism in Titanium Enolates: Catalytic Radical Haloalkylation and Application in the Total Synthesis of Neodysidenin

et al. 2010

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A direct ruthenium-catalyzed radical chloroalkylation of N-acyl oxazolidinones capitalizing on valence tautomerism of titanium enolates has been developed. The chloroalkylation method served as the centerpiece in the enantioselective total synthesis of trichloroleucine-derived marine natural product neodysidenin.Among more than four thousand halogenated natural products identified to date, 1 neodysidenin and other trichloroleucine-derived marine metabolites comprise a unique group. 2 For the majority of chlorinated natural products, a reasonable biosynthetic pathway involving an electrophilic chlorination can be proposed. 3 On the other hand, the trichloromethyl group in neodysidenin and related compounds arises from a remarkable direct chlorination of the pro-R methyl group of L-leucine carried out by nonheme Fe II halogenases requiring oxygen, chloride, and α-ketoglutarate for their activity. 4 In contrast, availability of synthetic methods for stereoselective trichloromethylation is highly limited, 5 whereas chlorinated natural products are attracting increasing attention as targets for chemical synthesis. 6 In this communication we describe a practical, efficient method for highly stereoselective direct chloroalkylation of titanium enolates and its application in the total synthesis of neodysidenin zakarian@chem.ucsb.edu. Supporting Information Available:Experimental procedures and copies of 1 H and 13 C NMR spectra. This information is available free of charge via the Internet at http://pubs.acs.org. that can be readily adopted for the synthesis of other bioactive natural products in this class. 7 Guided by an extension of the classic Kharasch reaction8 described by Eguchi and coworkers, 9 our early efforts involved Ru(II)-catalyzed 10 redox trichloromethylation of trimethylsilyl enol ethers generated from chiral N-acyl oxazolidinones such as 1 (Scheme 1). 11 Although encouraging results were obtained with silyl ketene acetals (~50% yields, ds 3:1), the recent characterization of valence tautomerism in titanium enolates provided a conceptual foundation for the development of a direct radical chloroalkylation of N-acyl oxazolidinones. NIH Public Access 12,13The unconventional biradical character of titanium enolates described by Moreira and coworkers suggests that these intermediates should be efficient radical acceptors. 7 Indeed, when the Ti enolate derived from 1 14 was treated with BrCCl 3 in the presence of [Ph 3 P] 3 RuCl 2 as a readily available redox catalyst (7 mol%), product 2 was obtained in an essentially quantitative yield with exquisite stereocontrol (Scheme 1). The the mechanistic hypothesis in Scheme 1 is based on well-established redox activity of [Ph 3 P] 3 RuCl 2 widely used in atom-transfer radical polymerization (ATRP) 15 and is similar to that proposed by Eguchi for a related process with silyl enol ethers.9 A major advantage, however, is that the radical addition product should be stabilized by electron delocalization onto titanium, not feasible with silyl enol ethers. Th...

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“…Moreira et al showed based on NMR, EPR, and computational studies that titanate enolates generated from TiCl 4 /a-alkoxy ketone complexes and tertiary amines display considerable biradical character. [12] These enolates must thus be considered unconventional valencetautomeric tetrachlorotitanate(IV) enolate/tetrachlorotitanate(III) a-carbonyl radical pairs 12/13 (Scheme 4).…”

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Perhaloalkylation of Metal Enolates—Unconventional and Versatile

Amatov

Jahn

2011

Angew Chem Int Ed

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Unconventional Biradical Character of Titanium Enolates

Abstract: Experimental and theoretical studies evidence an unconventional biradical character for the titanium enolates derived from α-alkoxy ketones and TiCl4. EPR experiments and ab initio calculations suggest that these titanium enolates have an open shell electronic ground state.

Cited by 47 publications

References 14 publications

Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

Valence Tautomerism in Titanium Enolates: Catalytic Radical Haloalkylation and Application in the Total Synthesis of Neodysidenin

Perhaloalkylation of Metal Enolates—Unconventional and Versatile

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