Driving Catalyst Reoxidation in Wacker Cyclizations with Acetal-Based Metal-Hydride Abstractors

Cochrane, Nikki A.; Brookhart, Maurice; Gagné, Michel R.

doi:10.1021/om2001958

Cited by 10 publications

(13 citation statements)

References 34 publications

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“…Given the noncoordinating feature of oxocarbenium ions, a classic inner‐sphere model could not explain this reaction. The ionic hydrogenation pattern is therefore highly favored in this case . The H 2 activation and hydride transfer are two key steps involved in the mechanism of hydrogenation reactions.…”

Section: Resultsmentioning

confidence: 90%

“…Anion binding by thiourea with substrates assists to achieve high efficiencies and high enantioselectivities in homogeneous hydrogenation of cationic C=N bonds present in iminium, (iso)quinolinium, and indolinium ions . We envisioned that this type of highly reactive intermediate could be captured by thiourea and be reduced by metal hydride complexes in an ionic hydrogenation manner . Herein, we report an iridium‐catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans smoothly with high enantioselectivities.…”

Section: Introductionmentioning

confidence: 99%

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Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

et al. 2020

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Ionic hydrogenation has not been extensively explored, but is advantageous for challenging substrates such as unsaturated intermediates. Reported here is an iridium‐catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans with high enantioselectivities. A variety of functionalities are compatible with this catalytic system. In the presence of a catalytic amount of the Brønsted acid HCl, an α‐chloroether is generated in situ and subsequentially reduced. Kinetic studies suggest first‐order kinetics in the substrate and half‐order kinetics in the catalyst. A positive nonlinear effect, together with the half kinetic order, revealed a dimerization of the catalyst. Possible reaction pathways based on the monomeric iridium catalyst were proposed and DFT computational studies revealed an ionic hydrogenation pathway. Chloride abstraction and the cleavage of dihydrogen occur in the same step.

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Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

et al. 2020

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“…Theionic hydrogenation pattern is therefore highly favored in this case. [16,27] TheH 2 activation and hydride transfer are two key steps involved in the mechanism of hydrogenation reactions.Here,wereport the results of our DFT calculations for the reaction mechanism. Fors implicity,t he results for some unfavorable pathways are given in the Supporting Information.…”

Section: Dft Calculations To Reveal An Ionic Hydrogenation Mechanismmentioning

confidence: 99%

“…[14] We envisioned that this type of highly reactive intermediate could be captured by thiourea [15] and be reduced by metal hydride complexes in an ionic hydrogenation manner. [16] Herein, we report an iridium-catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans smoothly with high enantioselectivities.…”

Section: Introductionmentioning

confidence: 99%

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

et al. 2020

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“…34 Under conditions analogous to the TrOMe reaction conditions, aromatic acetals like benzaldehyde dimethyl acetal and dimethoxymethane were effective (Scheme 3), and in the latter case provided Me 2 O as an easily removed volatile byproduct.…”

Section: Catalytic Oxidative Cascade Cyclizationsmentioning

confidence: 99%

Electrophilic Pt(II) Complexes: Precision Instruments for the Initiation of Transformations Mediated by the Cation–Olefin Reaction

2014

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A discontinuity exists between the importance of the cation–olefin reaction as the principal C–C bond forming reaction in terpene biosynthesis and the synthetic tools for mimicking this reaction under catalyst control; that is, having the product identity, stereochemistry, and functionality under the control of a catalyst. The main reason for this deficiency is that the cation–olefin reaction starts with a reactive intermediate (a carbocation) that reacts exothermically with an alkene to reform the reactive intermediate; not to mention that reactive intermediates can also react in nonproductive fashions. In this Account, we detail our efforts to realize catalyst control over this most fundamental of reactions and thereby access steroid like compounds. Our story is organized around our progress in each component of the cascade reaction: the metal controlled electrophilic initiation, the propagation and termination of the cyclization (the cyclase phase), and the turnover deplatinating events. Electrophilic Pt(II) complexes efficiently initiate the cation–olefin reaction by first coordinating to the alkene with selection rules that favor less substituted alkenes over more substituted alkenes. In complex substrates with multiple alkenes, this preference ensures that the least substituted alkene is always the better ligand for the Pt(II) initiator, and consequently the site at which all electrophilic chemistry is initiated. This control element is invariant. With a suitably electron deficient ligand set, the catalyst then activates the coordinated alkene to intramolecular addition by a second alkene, which initiates the cation–olefin reaction cascade and generates an organometallic Pt(II)-alkyl. Deplatination by a range of mechanisms (β-H elimination, single electron oxidation, two-electron oxidation, etc.) provides an additional level of control that ultimately enables A-ring functionalizations that are orthogonal to the cyclase cascade. We particularly focus on reactions that combine an initiated cyclization reaction with a turnover defining β-hydride elimination, fluorination, and oxygenation. These latter demetalation schemes lead to new compounds functionalized at the C3 carbon of the A-ring (steroid numbering convention) and thus provide access to interesting potentially bioactive targets. Progress toward efficient and diverse polycyclization reactions has been achieved by investing in both synthetic challenges and fundamental organometallic reactivity. In addition to an interest in the entrance and exit of the metal catalyst from this reaction scheme, we have been intrigued by the role of neighboring group participation in the cyclase phase. Computational studies have served to provide nuance and clarity on several key aspects, including the role (and consequences) of neighboring group participation in cation generation and stabilization. For example, these calculations have demonstrated that traversing carbonium ion transition states significantly impacts the kinetics of competitive 6-endo and 5-exo A-ring for...

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Driving Catalyst Reoxidation in Wacker Cyclizations with Acetal-Based Metal-Hydride Abstractors

Cited by 10 publications

References 34 publications

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

Electrophilic Pt(II) Complexes: Precision Instruments for the Initiation of Transformations Mediated by the Cation–Olefin Reaction

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