Nickel-Catalyzed Asymmetric Transfer Hydrogenation and α-Selective Deuteration of<i>N</i>-Sulfonyl Imines with Alcohols: Access to α-Deuterated Chiral Amines

Yang, Peng; Zhang, Li; Fu, Kaiyue; Sun, Yaxin; Wang, Xiuhua; Yue, Jie-Yu; Ma, Yu; Tang, Bo

doi:10.1021/acs.orglett.0c02921

Cited by 23 publications

(38 citation statements)

References 62 publications

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“…The latter substrate class has been subject of further studies, 272,273 resulting in the development of a photoredoxcatalyzed reduction using phenyl disulfide as HAT catalyst along with deuterium oxide (Scheme 88c) 274 as well as a nickelcatalyzed methodology for the enantioselective preparation of α-deuterated chiral N-tosyl-protected amines (Scheme 88d). 273 For the latter case, using deuterated isopropanol as deuterium source and a chiral ligand, an intermediary nickel deuteride complex selectively delivers the deuterium atom to the polarized sulfonylimine carbon atom in a stepwise manner, affording excellent yield, deuterium incorporation, and enantioselectivity. An external reductant is not needed as isopropanol additionally acts as a sacrificial reductant, affording acetone as the byproduct of the reduction.…”

Section: Reductive Deuteration Of Carbonyl Groupsmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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Organic compounds labeled with hydrogen isotopes play a crucial role in numerous areas, from materials science to medicinal chemistry. Indeed, while the replacement of hydrogen by deuterium gives rise to improved absorption, distribution, metabolism, and excretion (ADME) properties in drugs and enables the preparation of internal standards for analytical mass spectrometry, the use of tritium-labeled compounds is a key technique all along drug discovery and development in the pharmaceutical industry. For these reasons, the interest in new methodologies for the isotopic enrichment of organic molecules and the extent of their applications are equally rising. In this regard, this Review intends to comprehensively discuss the new developments in this area over the last years (2017−2021). Notably, besides the fundamental hydrogen isotope exchange (HIE) reactions and the use of isotopically labeled analogues of common organic reagents, a plethora of reductive and dehalogenative deuteration techniques and other transformations with isotope incorporation are emerging and are now part of the labeling toolkit.

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Section: Reductive Deuteration Of Carbonyl Groupsmentioning

confidence: 99%

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

et al. 2022

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“…In contrast, catalytic asymmetric deuteration approaches using prochiral or racemic substrates are still limited, mainly due to the challenges associated with identifying a chiral catalyst capable of binding with the commonly used deuterating reagents such as deuterium gas, deuterium oxide, and deuterated solvents. While the use of chiral transition metal complexes [14][15][16][17] , enzymes [18][19][20] , and small-molecule catalysts such as chiral phosphoric acids [21][22][23] have met with some success, deuterations are mostly restricted to benzylic positions in these studies. Moreover, from a mechanistic perspective, the deuteration event in the existing approaches typically proceeds through a two-electron manifold where the deuterium atom is introduced to stereocenters as a formal deuteride (D -) or deuteron (D + ) (Fig.…”

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confidence: 99%

Visible-light mediated catalytic asymmetric radical deuteration at non-benzylic positions

et al. 2022

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Site- and enantioselective incorporation of deuterium into organic compounds is of broad interest in organic synthesis, especially within the pharmaceutical industry. While catalytic approaches relying on two-electron reaction manifolds have allowed for stereoselective delivery of a formal deuteride (D–) or deuteron (D+) at benzylic positions, complementary strategies that make use of one-electron deuterium atom transfer and target non-benzylic positions remain elusive. Here we report a photochemical approach for asymmetric radical deuteration by utilizing readily available peptide- or sugar-derived thiols as the catalyst and inexpensive deuterium oxide as the deuterium source. This metal-free platform enables four types of deuterofunctionalization reactions of exocyclic olefins and allows deuteration at non-benzylic positions with high levels of enantioselectivity and deuterium incorporation. Computational studies reveal that attractive non-covalent interactions are responsible for stereocontrol. We anticipate that our findings will open up new avenues for asymmetric deuteration.

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“…Unfortunately, neither high conversion nor more than 34% ee could be achieved with Noyori-type, 12 iridium, 13 aluminum, 14 or nickel 15 catalysts and various reducing agents such as borohydrides, borane-complexes, or silanes with modified amino acids. 16 After unsuccessful attempts, the idea of asymmetric reduction was discarded.…”

Section: Special Topic Synthesismentioning

confidence: 99%

Synthesis of Racemic and Enantiopure Forms of β-Carboline Alkaloid Brevicolline

Milen¹,

Szabó²,

Görür³

et al. 2022

Synthesis

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A new total synthesis of the pharmacologically active β-carboline alkaloid brevicolline is described. The new synthetic approach is based on a commercially available and inexpensive starting material and reagents leading to a practical synthesis of the racemic target molecule, the natural (S)-enantiomer, and its antipode. Initially, the construction of the β-carboline skeleton and functionalization at the C(4) position have been accomplished. The formation of dihydropyrrole structural unit was obtained as the result of an Au-catalyzed hydroamination reaction, which was followed by a reduction that led to the chiral intermediate. The synthetic route described here is developed to ensure the sustainable access of the racemic brevicolline in 11 steps with improved 48% overall yield compared to the previously reported methods.

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Nickel-Catalyzed Asymmetric Transfer Hydrogenation and α-Selective Deuteration ofN-Sulfonyl Imines with Alcohols: Access to α-Deuterated Chiral Amines

Cited by 23 publications

References 62 publications

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

Visible-light mediated catalytic asymmetric radical deuteration at non-benzylic positions

Synthesis of Racemic and Enantiopure Forms of β-Carboline Alkaloid Brevicolline

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