Alkene <i>Syn</i>- and <i>Anti</i>-Oxyamination with Malonoyl Peroxides

Curle, Jonathan M.; Perieteanu, Marina C.; Humphreys, P. G.; Kennedy, Alan R.; Tomkinson, Nicholas C. O.

doi:10.1021/acs.orglett.0c00253

Cited by 11 publications

(8 citation statements)

References 47 publications

(33 reference statements)

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“…In these cases, the regioselectivity of oxyimination was guided by the stability of the radical after the addition of the O-radical to the alkene. Fascinatingly, successful dearomatization of a benzothiophene skeleton was achieved by employing this oxyimination protocol (24,25). The anti-geometry between the carbonate and iminyl functionality was confirmed from the crystal structure of 24 (Supplementary Figure 11).…”

Section: Reaction Scopementioning

confidence: 92%

“…48 Next, a series of disubstituted alkenes were evaluated in our oxyimination conditions. Different symmetrical as well as unsymmetrical 1,2-disubstituted olefins gave their desired products in respectable yields (21)(22)(23)(24)(25)(26). In these cases, the regioselectivity of oxyimination was guided by the stability of the radical after the addition of the O-radical to the alkene.…”

Section: Reaction Scopementioning

confidence: 99%

“…This further supports the proposed initial attack of the alkoxycarbonyloxyl radical to the alkene followed by the radical-radical cross coupling with the iminyl radical from the opposite, sterically accessible side. As a consequence, high diastereoselectivity was observed for different cyclic alkenes (21,22,24,25,26). Furthermore, six different 1,1-disubstituted alkenes were investigated in order to synthesise 2-amino-1-alcohols with a tertiary alkylamine centre (27)(28)(29)(30)(31)(32).…”

Section: Reaction Scopementioning

confidence: 99%

“…Alternatively, a two-step aziridination of alkene followed by nucleophilic ring opening can also deliver a similar regioselective outcome. [23][24][25] However, low nucleophilicity of alcohols poses a significant challenge.…”

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confidence: 99%

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Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

et al. 2021

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The 1,2-aminoalcohol motif is one of the most prevalent structural components found in high-value organic molecules including pharmaceuticals and natural products. Generally, their preparation requires pre-functionalised substrates and manipulations of one functional group at a time to achieve the desired regioisomer. Herein, we describe a metal-free photosensitisation protocol for the installation of both amine and alcohol functionalities into alkene feedstocks in a single step. This approach is enabled by the identification of oxime carbonate as a suitable bifunctional source of both oxygen-and nitrogen-centred radicals for addition across alkenes with complementary regioselectivity compared to Sharpless aminohydroxylation. Use of orthogonal protection for amine and alcohol functionalities enables direct synthetic diversifications of one functional handle without influencing the other. With the use of readily available starting materials, convergent synthesis and mild reaction conditions, this process is well suited for use in various synthetic endeavors.The vicinal aminoalcohol motif is one of the most abundant structural units in natural products, pharmaceuticals, agrochemicals and privileged ligands. [1][2][3] Synthetic routes to this motif rely typically on multistep, iterative manipulations of functional groups to introduce both amine and alcohol functionalities in their desired positions. [4][5][6] Usually transition metal-catalysed directed β-C-H functionalisation of alcohols or amines offers a synthetic alternative with the necessity of a preinstalled directing group. [7][8][9][10] Nevertheless, all these approaches involve manipulation of one functional group at a time (Fig. 1a). By comparison, aminohydroxylation of alkenes is the most straightforward yet powerful approach for the synthesis of 1-amino-2-alcohols allowing simultaneous introduction of both functionalities into the molecule in a single step, as pioneered by Sharpless. 11,12 The generality of this approach however is often plagued by poor regioselectivity and the need for N-haloamides. 13 The use of a similar concept to synthesise 2-amino-1-alcohol skeleton requires a complete regioselectivity switch and remains a challenge to date (Fig. 1b). 14,15 So far, transient N-centred radical initiated aminohydroxylation strategy has been exploited in different intramolecular cyclisation context through ingenious substrate design to generate 2-amino-1-alcohol framework. [16][17][18][19] Clearly, lack of substrate generality and intramolecular nature of these transformations obviates there widespread use. In this regard, Yoon has elegantly utilized high strain of oxaziridine ring in aminal synthesis with analogous regioselectivity. [20][21][22] However, the requirement for initial radical attack by the alkene substrate to the copper-activated oxaziridine limits the use of unactivated alkenes in this aminohydroxylation approach. Alternatively, a two-step aziridination of alkene followed by nucleophilic ring opening can also deliver a similar regiosel...

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Section: Reaction Scopementioning

confidence: 92%

Section: Reaction Scopementioning

confidence: 99%

Section: Reaction Scopementioning

confidence: 99%

mentioning

confidence: 99%

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Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

et al. 2021

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“…Despite its effectiveness, particularly for enantioselective versions, the high toxicity of osmium limits the application of this method. Therefore, many groups have developed alternative protocols using different families of amine precursors and catalysts, mainly based on palladium, rhodium, and copper. , In order to promote a more sustainable approach, the development of methods based on the use of iron as a cheap, highly abundant, and nontoxic metal appears highly desirable. Iron-catalyzed oxyamination procedures have thus been recently investigated.…”

Section: Introductionmentioning

confidence: 99%

Iron-Catalyzed Intermolecular Oxyamination of Terminal Alkenes Promoted by HFIP Using Hydroxylamine Derivatives

2023

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An atom-economical intermolecular iron-catalyzed oxyamination of alkenes is described herein. The insertion of oxygenated and nitrogenated moieties from the hydroxylamine substrate was observed with full regio-and chemo-selectivity for terminal alkenes in good yields. HFIP as a solvent appeared to have a synergistic effect with the iron catalyst to promote the formation of the oxyaminated products. Preliminary mechanistic studies suggest a pathway going through an aziridination reaction followed by an in situ ring opening.

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Transition‐Metal‐Catalyzed Aminooxygenation of Alkenes

Chemler¹,

Chen²,

Karyakarte³

et al. 2021

Organic Reactions

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Alkene aminooxygenation reactions provide vicinal amino alcohol derivatives, moieties that frequently appear in catalysts, drugs, and other valuable molecules. This Chapter reviews transition‐metal‐catalyzed aminooxygenations of alkenes and aims to serve as a guide in the selection of appropriate reagents and procedures for specific substrate classes and desired transformations. Inter‐ and intramolecular aminooxygenation reactions catalyzed by osmium, palladium, platinum, gold, copper, iron, iridium, rhodium, ruthenium, and manganese are presented, as is a discussion of the factors involved in reactivity and selectivity. A brief section on non‐metal catalyzed alkene aminohydroxylation is also included. A complete set of alkene aminooxygenation reactions through mid‐2020 is provided in the Tabular Survey.

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Alkene Syn- and Anti-Oxyamination with Malonoyl Peroxides

Cited by 11 publications

References 47 publications

Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

Iron-Catalyzed Intermolecular Oxyamination of Terminal Alkenes Promoted by HFIP Using Hydroxylamine Derivatives

Transition‐Metal‐Catalyzed Aminooxygenation of Alkenes

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