Directed ortho metalation of N,N-diethylbenzamides. Silicon protection of ortho sites and the o-methyl group

Mills, Robert J.; Taylor, Nicholas J.; Snieckus, Victor

doi:10.1021/jo00279a028

Cited by 142 publications

(74 citation statements)

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“…Consequently, the processes are competitive and, as such, result from the presence of similar directing agents. Recently, ring substitution and lateral-group branching [5] have been employed, in addition to the use of a-silyl lateral groups, [6] as means of controlling the regioselectivity of deprotonation. The use of deuterium as a protecting group at kinetically acidic positions has been reported both for amides [7] and N-heterocyclic systems.…”

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confidence: 99%

Controlling Chemoselectivity in the Lithiation of Substituted Aromatic Tertiary Amides

Armstrong

Boss

Clayden³

et al. 2004

Angew Chem Int Ed

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Aromatic compounds can be elaborated by directed lithiation in a number of ways [1] and both ortho and lateral metallation have been employed as synthetic tools generally [2] and in a host of recent total syntheses specifically. [3,4] Whereas ortho metallation occurs both because the directing group can inductively raise the acidity of the ortho hydrogen atom and also because the incoming organometallic substrate closely approaches this position, lateral metallation results from the directing function coordinating an organometallic substrate whilst conjugatively withdrawing electrons from a benzylic group. Consequently, the processes are competitive and, as such, result from the presence of similar directing agents. Recently, ring substitution and lateral-group branching [5] have been employed, in addition to the use of a-silyl lateral groups, [6] as means of controlling the regioselectivity of deprotonation. The use of deuterium as a protecting group at kinetically acidic positions has been reported both for amides [7] and N-heterocyclic systems. [8] Overall, studies to date have clearly established that, for either class of reaction, amide-type groups are among the most useful directors of reaction.[2]Transformations of ortho-and laterally lithiated tertiary amides have been investigated, [9] with directing effects having been attributed to the rate-determining deprotonation of a substrate-organolithium complex. [10][11][12] However, it is only very recently that solid-state structural evidence has been presented in support of the nature of lithiated intermediates in either reaction pathway. For 1 and 2 ortho lithiation has led to the characterization of solid-state dimers, 3, and isostructural N,N-diisopropyl-2-lithionaphthamide-THF complex, 4, respectively. These are based on core C···Li interactions, support of the metals coming from (amide)OÀLi bonding with concomitant modulation of the sterically induced twist angle between the amide and the plane of the aromatic ring.[13] Contrastingly, the laterally deprotonated salt of 5 reveals a tris(thf) solvate, 6, in which the metal center is only coordinated by O atoms with no C···Li interaction, thus allowing the amide and aromatic planes to be near to perpendicular in the solid state.[14] These data suggest a link between the number of donor atoms per solvent molecule (solvent denticity) and reaction chemoselectivity and lead us to report here on the competitive deprotonation of 2-ethyl-N,N-diisopropyl-1-benzamide, 7.Treatment of 7 in THF/toluene at À78 8C with 1 equivalent of tBuLi gave a maroon solution from which, on storage at À30 8C, crystals were deposited. Surprisingly, in light of previous work, [2,12,15] these were identified as N,N-diisopropyl-2-ethyl-6-lithiobenzamide-THF, 8, by X-ray crystallography. [16] In accordance with our own recent studies, [13] 8 forms a solid-state dimer based on the stabilization of each metal component in a {(CLi) 2 } core (C2ÀLi1 = 2.345(5) , C2A À Li1 = 2.187(5) ] by an amide-O center (O1 À Li1 = 1.972(5) ) and one THF m...

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confidence: 99%

Controlling Chemoselectivity in the Lithiation of Substituted Aromatic Tertiary Amides

Armstrong

Boss

Clayden³

et al. 2004

Angew Chem Int Ed

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“…[13] We chose the ortho-protected O- (4-[2.2]paracyclophanyl) diisopropylcarbamates 3a and 3b for studies of this homologous anionic Fries rearrangement, since the trialkylsilyl groups are easily removable by fluoride sources. [10,14] Compounds 3a and 3b were readily prepared from 4-hydroxy- [2.2]paracyclophane [15] (1) by carbamoylation to 2 followed by standard directed ortho-metalation (DoM) [14] and silylation with TMSCl and TESCl, respectively (Scheme 1). The application of the DoM strategy to O-( [2.2]paracycloScheme 1.…”

Section: Rearrangement Of Ortho-protected O-([22]paracyclophanyl) DImentioning

confidence: 99%

“…[2,9] In contrast, Snieckus et al showed that prior silicon protection of preferred ortho-metalation sites makes alternate ring remote deprotonation possible. [10,11] An application of this methodology is the synthesis of dibenzo[bd]pyranones from O-(o-biaryl) carbamates by a remote anionic Fries rearrangement. [11] Here we report two methods for the stereoselective functionalization of one ethano bridge in monosubstituted [2.2]paracyclophanes.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Lateral Functionalization of Monosubstituted [2.2]Paracyclophanes by Directedortho-Metalation−Homologous Anionic Fries Rearrangement

et al. 2001

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“…Preparation of the iodide 5 was achieved according to Snieckus's procedure. [12] The coupling reaction of 5 with alkenylstannane 8 gave the desired alkenylated product in good yield. OsO 4 -catalyzed dihydroxylation and silylation proceeded smoothly to give the type B compound 9 b.…”

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Importance of Interaction between C1 Domain and Lipids in Protein Kinase Cα Activation: Hydrophobic Side Chain Direction in Isobenzofuranone Ligands Controls Enzyme Activation Level

et al. 2007

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Directed ortho metalation of N,N-diethylbenzamides. Silicon protection of ortho sites and the o-methyl group

Cited by 142 publications

References 0 publications

Controlling Chemoselectivity in the Lithiation of Substituted Aromatic Tertiary Amides

Controlling Chemoselectivity in the Lithiation of Substituted Aromatic Tertiary Amides

Stereoselective Lateral Functionalization of Monosubstituted [2.2]Paracyclophanes by Directedortho-Metalation−Homologous Anionic Fries Rearrangement

Importance of Interaction between C1 Domain and Lipids in Protein Kinase Cα Activation: Hydrophobic Side Chain Direction in Isobenzofuranone Ligands Controls Enzyme Activation Level

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