Oxidative Kinetic Resolution of Cyclic Benzylic Ethers

et al. 2022

Nat Commun

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Catalytic nonenzymatic kinetic resolution (KR) of racemates remains one of the most powerful tools to prepare enantiopure compounds, which dominantly relies on the manipulation of reactive functional groups. Moreover, catalytic KR of organic azides represents a formidable challenge due to the small size and instability of the azido group. Here, an effective KR of cyclic benzylic azides through site- and enantioselective C(sp3)–H oxidation is described. The manganese catalyzed oxidative KR reaction exhibits good functional group tolerance, and is applicable to a range of tetrahydroquinoline- and indoline-based organic azides with excellent site- and enantio-discrimination. Computational studies elucidate that the effective chiral recognition is derived from hydrogen bonding interaction between substrate and catalyst.

Section: Introductionmentioning

confidence: 99%

Kinetic resolution of cyclic benzylic azides enabled by site- and enantioselective C(sp3)–H oxidation

Feng

et al. 2022

Nat Commun

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“…In addition, some 1,3‐dihydroisobenzofuran derivatives can be used as inhibitors of a variety of biological enzymes, such as peptide deformylase, [1b] glutathione S‐transferase [1c] (Figure 1). In the past few decades, strategies for the synthesis of 1,3‐dihydroisobenzofurans have been intensively developed, most of which involve the use of transition‐metals such as Rh, Pd, Au, Ag, Cu and Mn through a cyclization process [2–7] . Besides, some metal‐free synthetic methods of 1,3‐dihydroisobenzofurans have also been disclosed [8–10] .…”

Section: Introductionmentioning

confidence: 99%

“…In the past few decades, strategies for the synthesis of 1,3-dihydroisobenzofurans have been intensively developed, most of which involve the use of transitionmetals such as Rh, Pd, Au, Ag, Cu and Mn through a cyclization process. [2][3][4][5][6][7] Besides, some metal-free synthetic methods of 1,3-dihydroisobenzofurans have also been disclosed. [8][9][10] On the other hand, indanones constitute the core structure of many natural products, biologically active molecules, and functional materials.…”

Section: Introductionmentioning

confidence: 99%

DBU/AgOTf Relay‐Catalysis Enabled One‐Pot Synthesis of 1,3‐Dihydroisobenzofurans and Its Conversion to Indanones

Huang

et al. 2022

Adv Synth Catal

A DBU/AgOTf relay-catalyzed one-pot reaction of 2-alkynylbenzaldehydes and α-diazo esters for the efficient construction of 1,3-dihydroisobenzofuran derivatives has been documented. This protocol can tolerate a wide range of substrates and its scalability is demonstrated by the gram-scale reaction. Moreover, the obtained 1,3-dihydroisobenzofurans can be converted to indanone derivatives by a AgOTf-catalyzed ring recombination process. Both of the resulting products, 1,3-dihydroisobenzofurans and indanones, are important structural units of a variety of pharmaceuticals and natural products, and their structures are clearly confirmed by single crystal X-ray diffraction analysis.

“…Oxygen atom transfer (OAT) reaction is ubiquitous in biological systems, organic synthesis, and industrial processes 19 – 23 . Current asymmetric OAT studies predominantly focused on oxygenation of alkenes and sulfides involving C–O and S–O bond formation 24 – 34 . We envisioned that asymmetric OAT to secondary amines to produce enantiopure hydroxylamines involving N–O bond formation would be an ideal template for KR design based on economical and environmental factors (Fig.…”

Section: Introductionmentioning

confidence: 99%

Kinetic resolution of indolines by asymmetric hydroxylamine formation

et al. 2021

Nat Commun

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Catalytic kinetic resolution of amines represents a longstanding challenge in chemical synthesis. Here, we described a kinetic resolution of secondary amines through oxygenation to produce enantiopure hydroxylamines involving N–O bond formation. The economic and practical titanium-catalyzed asymmetric oxygenation with environmentally benign hydrogen peroxide as oxidant is applicable to a range of racemic indolines with multiple stereocenters and diverse substituent patterns in high efficiency with efficient chemoselectivity and enantio-discrimination. Late-stage asymmetric oxygenation of bioactive molecules that are otherwise difficult to synthesize was also explored.