Allylic CH Alkylation of Unactivated α‐Olefins: Serial Ligand Catalysis Resumed

Young, Andrew J.; White, M. Christina

doi:10.1002/anie.201101654

Cited by 138 publications

(37 citation statements)

References 50 publications

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“…The predominance of unbound Pd(OAc) 2 in the presence of PhS(O)C 2 H 4 S(O)Ph has also been observed experimentally. 56,57 In contrast, the Pd(OAc) 2 /4,5-diazafluorenone complex is exergonic by 4.2 kcal/mol with respect to unbound Pd(OAc) 2 , indicating that the latter is not the resting state in this catalytic system (see the Supplementary Information for details). We also considered the involvement of a Lewis base-coordinated Pd-π-allyl species in these studies of theoretical binding affinities (see the Supplementary Information for further details).…”

Section: Resultsmentioning

confidence: 99%

Non-directed allylic C–H acetoxylation in the presence of Lewis basic heterocycles

Malik¹,

Taylor

Kerrigan³

et al. 2014

Chem. Sci.

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We outline a strategy to enable non-directed Pd(II)-catalyzed C–H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen of two Pd-catalyzed C–H acetoxylation reactions, addition of a variety of N-containing heterocycles is found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest. We pursue two approaches in parallel that allow product conversion in this representative system: Lewis acids are found to be effective in situ blocking groups for the Lewis basic site, and a pre-formed pyridine N-oxide is shown to enable high yield of allylic C–H acetoxylation. Computational studies with density functional theory (M06) of binding affinities of selected heterocycles to Pd(OAc)2 provide an inverse correlation of the computed heterocycle–Pd(OAc)2 binding affinities with the experimental conversions to products. Additionally, 1H NMR binding studies provide experimental support for theoretical calculations.

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Section: Resultsmentioning

confidence: 99%

Non-directed allylic C–H acetoxylation in the presence of Lewis basic heterocycles

Malik¹,

Taylor

Kerrigan³

et al. 2014

Chem. Sci.

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“…Within recent years, our laboratory has introduced electrophilic Pd(II)/sulfoxide catalysis as a general platform for allylic C–H activation that enables direct allylic esterification, 12 amination, 13 and alkylation 14 of terminal olefins through the intermediacy of a π-allylPd species. We hypothesized that a dehydrogenation reaction of terminal olefins could also be developed using this reaction manifold by promoting β-hydride elimination from the π-allylPd intermediate, in the absence of nucleophile.…”

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confidence: 99%

“…18 While the use of Pd(OAc) 2 resulted in only recovered starting material (entry 1), Pd(II)/phenylbis-sulfoxide catalyst 1 provided initial dehydrogenation reactivity, albeit in low yield (6% yield of 3a , entry 2). After a survey of ligands, it was found that 10 mol% of the Pd(II)/benzylbis-sulfoxide catalyst 2 12a,14b,14c resulted in higher catalytic turnover, leading to 28% diene product (4:1 E:Z selectivity, entry 3). Longer reaction times led to significantly diminished yields, indicating that the 1,3-butadiene product was not stable to the reaction conditions.…”

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confidence: 99%

Molecular Complexity via C–H Activation: A Dehydrogenative Diels–Alder Reaction

2011

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Traditionally, C–H oxidation reactions install oxidized functionality onto a preformed molecular skeleton, resulting in a local molecular change. The use of C–H activation chemistry to construct complex molecular scaffolds is a new area with tremendous potential in synthesis. We report a Pd(II)/bis-sulfoxide catalyzed dehydrogenative Diels-Alder reaction that converts simple terminal olefins into complex cycloadducts in a single operation.

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“…3,4 Unfortunately, C–H alkylation methods have been limited in scope to disubstituted methylene nucleophiles bearing two electron-withdrawing groups (Scheme 1A). Previous reports employing tertiary nucleophiles in allylic C–H alkylation reactions have been limited with respect to either olefin scope (i.e., only 1,4-dienes) or nucleophile scope (i.e., tetralones) (Scheme 1B).…”

Section: Introductionmentioning

confidence: 99%

General Allylic C–H Alkylation with Tertiary Nucleophiles

et al. 2014

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A general method for intermolecular allylic C–H alkylation of terminal olefins with tertiary nucleophiles has been accomplished employing palladium(II)/bis(sulfoxide) catalysis. Allylic C–H alkylation furnishes products in good yields (avg. 64%) with excellent regio- and stereoselectivity (>20:1 linear:branched, >20:1 E:Z). For the first time, the olefin scope encompasses unactivated aliphatic olefins as well as activated aromatic/heteroaromatic olefins and 1,4-dienes. The ease of appending allyl moieties onto complex scaffolds is leveraged to enable this mild and selective allylic C–H alkylation to rapidly diversify phenolic natural products. The tertiary nucleophile scope is broad and includes latent functionality for further elaboration (e.g., aliphatic alcohols, α,β-unsaturated esters). The opportunities to effect synthetic streamlining with such general C–H reactivity are illustrated in an allylic C–H alkylation/Diels–Alder reaction cascade: a reactive diene is generated via intermolecular allylic C–H alkylation and approximated to a dienophile contained within the tertiary nucleophile to furnish a common tricyclic core found in the class I galbulimima alkaloids.

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Allylic CH Alkylation of Unactivated α‐Olefins: Serial Ligand Catalysis Resumed

Cited by 138 publications

References 50 publications

Non-directed allylic C–H acetoxylation in the presence of Lewis basic heterocycles

Non-directed allylic C–H acetoxylation in the presence of Lewis basic heterocycles

Molecular Complexity via C–H Activation: A Dehydrogenative Diels–Alder Reaction

General Allylic C–H Alkylation with Tertiary Nucleophiles

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