Enantioselective Organocatalytic Addition of Nitromethane to Trifluoromethyl Aryl Ketimines Promoted by Electron‐Rich Bifunctional Iminophosphoranes

Krstić, Marija; Benaglia, Maurizio; Gazzotti, M.; Colombo, Eleonora; Sanz, Miguel Á.

doi:10.1002/adsc.202201297

Cited by 5 publications

(6 citation statements)

References 43 publications

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“…No product was detected without a base (Table 1, entry 23). The absolute stereochemistry of 3a was determined to be S by comparing its optical rotation with the reported value (Krstic et al, 2023).…”

Section: Resultsmentioning

confidence: 99%

“…Wang (Xie et al, 2011), Liu (Zhang et al, 2011;Li et al, 2019), and Nenajdenko (Kutovaya et al, 2015) have reported several notable contributions to this field. In addition, Duan (Wang et al, 2019a) and Krstic et al (2023) reported Frontiers in Chemistry frontiersin.org the asymmetric aza-Henry reaction of trifluoromethyl ketimines using different kinds of ion-pair catalysts (Schemes 1A, and B). Despite these advances, the synthesis of chiral trifluoromethyl amines using readily prepared catalysts with low catalyst loading still remains a challenging goal for organic chemists (Onyeagusi and Malcolmson, 2020).…”

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confidence: 99%

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Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Ren,

Du,

Peng

et al. 2024

Front. Chem.

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Amino acid-derived quaternary ammonium salts were successfully applied in the asymmetric aza-Henry reaction of nitromethane to N-Boc trifluoromethyl ketimines. α-Trifluoromethyl β-nitroamines were synthesized in good to excellent yields with moderate to good enantioselectivities. This reaction is distinguished by its mild conditions, low catalyst loading (1 mol%), and catalytic base. It also proceeded on a gram scale without loss of enantioselectivity. The products were transformed to a series of adamantane-type compounds containing chiral trifluoromethylamine fragments. The potent anticancer activities of these compounds against liver cancer HepG2 and melanoma B16F10 were evaluated. Six promising compounds with notable efficacy have potential for further development.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Ren,

Du,

Peng

et al. 2024

Front. Chem.

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“…In our own work (Scheme 1, D1), phenol nucleophiles were used in the desymmetrization step under ureidopeptide [148][149][150][151][152][153][154] bifunctional iminophosphorane (BIMP) catalysis, [155][156][157][158][159][160][161][162][163][164][165][166][167][168] however, to obtain high levels of enantioselectivity, phenol nucleophiles bearing an ortho-substituent were required, inherently limiting the scope of the reaction. Additionally, the optimal leaving group, 2-nitro-6-methyl-phenolate, 169 is a relatively weak Brønsted base, rendering the turnover of the optimal superbasic BIMP catalyst inefficient, which, in turn, forces an excessive 15 mol% catalyst loading to ensure high conversion of the starting material to product.…”

Section: Methodsmentioning

confidence: 99%

Second Generation Catalytic Enantioselective Nucleophilic Desymmetrization at P(V): Improved Generality, Efficiency and Modularity

Formica,

Ferko,

Marsh

et al. 2023

Preprint

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A second generation catalytic two-phase strategy for the enantioselective synthesis of chiral at P(V) compounds is described. This protocol, consisting of a bifunctional iminophosphorane (BIMP) catalyzed nucleophilic desymmetrization of prochiral, bench stable P(V) precursors and subsequent enantiospecific substitution allows for divergent access to a wide range of C-, N-, O- and S- substituted P(V) containing compounds from a handful of enantioenriched precursors. A new catalyst/leaving group combination allowed for a far wider substrate scope and increased reaction efficiency and practicality over previously established protocols. The resulting enantioenriched intermediates could then be converted to an even greater range of distinct classes P(V) of compounds by displacement of the remaining leaving group as well as allowing for even further diversification downstream. Density functional theory (DFT) calculations were performed to pinpoint the origin of enantioselectivity for the BIMP-catalyzed desymmetrization, to rationalize how a superior catalyst/leaving group combination leads to increased generality in our second-generation catalytic system, as well as to shed light onto observed retention and inversion pathways when performing late-stage enantiospecific SN2@P reactions with Grignard reagents.

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“…Interestingly, the bifunctional iminophosphorane−thioureabased iminophosphorane (BIMP) organocatalyst featuring a BIDIME iminophosphorane unit and thiourea motif was able to mediate the enantioselective addition of nitromethane to trifluoromethyl aryl ketimines to furnish α-trifluoromethyl-βnitroamines in good yields and enantioselectivities (Scheme 60). 116…”

Section: Asymmetric Addition To C−n Double Bondsmentioning

confidence: 99%

“…Scheme 60. Enantioselective Organocatalytic Addition of Nitromethane to Trifluoromethyl Aryl Ketimines116 …”

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confidence: 99%

Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

Cao,

He,

Tang

2024

Org. Process Res. Dev.

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P-Chiral phosphorus ligands received little attention in organic chemistry until Knowles made his landmark contribution in asymmetric hydrogenation by developing the P-chiral ligands CAMP and DIPAMP. The development of P-chiral phosphorus ligands accelerated in the end of the last century with the advent of some highly efficient and renowned ligands for asymmetric hydrogenation, including BisP*, TangPhos, QuinoxP*, DuanPhos, et al. However, most reported ligands were airsensitive, difficult to make, or lacked structural modularity, hampering their availability and applicability. The development of sterically and electronically tunable P-chiral phosphorus ligands is particularly desirable. Over the past decade, a family of sterically hindered, electron-rich, structurally tunable, and air-stable P-chiral dihydrobenzooxaphosphole ligands emerged that proved to be efficient and versatile for various asymmetric transformations. The last 5 years witnessed an increasing number of studies related to these ligands with the discovery of their unprecedented catalytic properties in various transformations. This review highlights the unique properties of P-chiral dihydrobenzooxaphosphole ligands in catalysis and their applications in the synthesis of natural products and therapeutic agents.

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Enantioselective Organocatalytic Addition of Nitromethane to Trifluoromethyl Aryl Ketimines Promoted by Electron‐Rich Bifunctional Iminophosphoranes

Cited by 5 publications

References 43 publications

Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Asymmetric aza-Henry reaction toward trifluoromethyl β-nitroamines and biological investigation of their adamantane-type derivatives

Second Generation Catalytic Enantioselective Nucleophilic Desymmetrization at P(V): Improved Generality, Efficiency and Modularity

Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

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