Synthetic applications of hydride abstraction reactions by organic oxidants

Miller, Jenna; Lawrence, Jean-Marc I A; Rey, Freddy O. Rodriguez del; Floreancig, Paul E.

doi:10.1039/d1cs01169c

Cited by 29 publications

(24 citation statements)

References 222 publications

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“…It has been reported that heteroatom-containing substrates can be oxidized by DDQ to generate oxocarbenium or iminium ion species through a hydride abstraction mechanism. 27 Thus, hydride abstraction of THIQ 4 by DDQ in the presence of TFA forms iminium-trifluoroacetate complex Int-1 , which undergoes allylation to afford the desired product 5 . For catalytic cycle, molecular oxygen plays a critical role to form NO 2 , which could oxidize DDQH 2 back to DDQ.…”

Section: Resultsmentioning

confidence: 99%

“…A possible mechanism of the DDQ-catalyzed allylation under aerobic condition is proposed in Scheme . It has been reported that heteroatom-containing substrates can be oxidized by DDQ to generate oxocarbenium or iminium ion species through a hydride abstraction mechanism . Thus, hydride abstraction of THIQ 4 by DDQ in the presence of TFA forms iminium-trifluoroacetate complex Int-1 , which undergoes allylation to afford the desired product 5 .…”

Section: Resultsmentioning

confidence: 99%

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Stereoselective Synthesis of Benzo[a]quinolizidines via Aerobic DDQ-Catalyzed Allylation and Reductive Cyclization

et al. 2022

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Stereoselective synthesis of C 4 -substituted benzo[ a ]quinolizidines via redox-controlled catalytic C–C-bond-forming reactions was carried out. Aerobic DDQ-catalyzed allylation of N -Cbz tetrahydroisoquinolines efficiently provided α-allylated products 5 , which were transformed to enones 6 via cross-metathesis reactions using the second-generation Hoveyda–Grubbs catalyst. Palladium-catalyzed hydrogenation of 6 prompted alkene reduction, protecting group removal, and intramolecular reductive amination in one step to afford the desired benzo[ a ]quinolizidines 7 as single diastereomers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Stereoselective Synthesis of Benzo[a]quinolizidines via Aerobic DDQ-Catalyzed Allylation and Reductive Cyclization

et al. 2022

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“…15 We envisioned that changing the oxidative C−H bond-cleavage pathway from HAT to direct hydride abstraction would be beneficial to diastereoselective reaction design. 13 Common organic hydride abstracting agents include quinones, oxoammonium ions, and triarylmethyl (trityl) cations. 16 Accordingly, these three types of hydride abstracting agents have been comprehensively explored during the methodology development process.…”

Section: Diastereoselective Intermolecular Oxidative C−h Functionaliz...mentioning

confidence: 99%

“…), and long reaction times, all of which are generally disadvantageous for achieving stereoselective variants . We envisioned that changing the oxidative C–H bond-cleavage pathway from HAT to direct hydride abstraction would be beneficial to diastereoselective reaction design …”

Section: Hydride-abstraction-initiated Diastereoselective Intermolecu...mentioning

confidence: 99%

Hydride-Abstraction-Initiated Catalytic Stereoselective Intermolecular Bond-Forming Processes

Liu

2022

Acc. Chem. Res.

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Conspectus The stereoselective intermolecular bond-forming reactions through the direct manipulation of ubiquitous yet inert C(sp3)–H bonds represent an important and long-standing goal in chemistry. In particular, developing such a stereoselective bimolecular transformation involving carbocation intermediates generated via site-selective hydride abstraction or formal hydride abstraction by organic oxidants would avoid the preinstallation of directing groups and is therefore attractive. Hydride-abstraction-initiated bimolecular transformations have received considerable attention, but existing examples lack stereoselective studies. Prevalent stereoselective studies typically suffer from the narrow substrate scope of specific and highly reactive N-aryl amines and diarylmethanes together with limited synthetic utility. This Account describes our recent advances in the development and synthetic application of hydride-abstraction-initiated stereoselective intermolecular C–C and C–H bond-forming processes with significantly expanded scopes involving structurally diverse N-acyl amines and ethers together with nitriles, esters, and perfluoroalkyl moieties. We first explored hydride-abstraction-initiated stereoselective intermolecular C–C bond-forming processes. Utilizing triarylmethyl cations or oxoammonium ions as hydride abstractors, we accomplished the diastereoselective oxidative C–H functionalization of structurally diverse N-acyl amines and ethers with a range of organoboranes and C–H components, efficiently installing a series of alkyl, alkenyl, aryl, and alkynyl species into the α-position of heteroatoms with good levels of diastereocontrol. Subsequently, we developed an “acetal pool” strategy as the toolbox to regulate the stability of cationic intermediates and the compatibility of organic oxidants with a delicate asymmetric catalysis system. Utilizing this strategy, we achieved the catalytic enantioselective oxidative C–H alkenylation, arylation, alkynylation, and alkylation of diverse N-acyl heterocycles with a range of boronates and C–H components. Simultaneously, we extended this strategy to the asymmetric oxidative C–H alkylation of ethers. Notably, the method allows solvents that are used daily, such as tetrahydrofuran, tetrahydropyran, and diethyl ether, to be facilely transformed to high-value-added optically pure bioactive molecules. We further expanded the scope of this challenging area from the C(sp3)–H bond adjacent to electron-donating heteroatoms to valuable electron-withdrawing functional groups including nitriles, esters, and perfluoroalkyl moieties for the stereoselective construction of single and vicinal quaternary carbon stereocenters, respectively. We studied hydride-abstraction-initiated catalytic asymmetric intermolecular C–H bond-forming processes, known as redox deracemization. Utilizing the acetal pool strategy, we reported the first redox deracemization of cyclic benzylic ethers. Later, we disclosed an aerobic one-pot deracemization of diverse α-amino acid derivatives with excellent ...

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“…Based on the known ability of lithium amides (e.g., 1 ) to undergo imine formation (e.g., 2 ) upon reducing simple ketones, , a process that we have found to be rapid for lithium amides derived from alicyclic amines, we recently developed a new strategy for amine α-C–H bond functionalization (Scheme d) . Various α-functionalized amines can be accessed with this approach.…”

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confidence: 99%

Regioselective α-Cyanation of Unprotected Alicyclic Amines

Valles

Chen

et al. 2022

Org. Lett.

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Secondary alicyclic amines are converted to α-aminonitriles via addition of TMSCN to their corresponding imines, intermediates that are produced in situ via the oxidation of amine-derived lithium amides with simple ketone oxidants. Amines with an existing α-substituent undergo regioselective α′cyanation even if the C−H bonds at that site are less activated. Amine α-arylation can be combined with α′-cyanation to generate difunctionalized products in a single operation.

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Synthetic applications of hydride abstraction reactions by organic oxidants

Abstract: Organic oxidants, including quinones, oxoammonium ions, and trityl cations, abstract hydride ions to form carbocations. This review describes the mechanistic foundations for these processes and the vast array of their applications in synthesis.

Cited by 29 publications

References 222 publications

Stereoselective Synthesis of Benzo[a]quinolizidines via Aerobic DDQ-Catalyzed Allylation and Reductive Cyclization

Stereoselective Synthesis of Benzo[a]quinolizidines via Aerobic DDQ-Catalyzed Allylation and Reductive Cyclization

Hydride-Abstraction-Initiated Catalytic Stereoselective Intermolecular Bond-Forming Processes

Regioselective α-Cyanation of Unprotected Alicyclic Amines

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