Alkene oxyamination using malonoyl peroxides: preparation of pyrrolidines and isoxazolidines

Carla Alamillo-Ferrer; Jonathan M Curle; Stuart C Davidson; Simon C C Lucas; Stephen J Atkinson; Matthew Campbell; Alan R Kennedy; Nicholas C O Tomkinson

doi:10.1021/acs.joc.8b00392

Alkene oxyamination using malonoyl peroxides: preparation of pyrrolidines and isoxazolidines

Carla Alamillo-Ferrer, Jonathan M Curle, Stuart C Davidson, Simon C C Lucas, Stephen J Atkinson, Matthew Campbell, Alan R Kennedy, Nicholas C O Tomkinson

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Abstract

Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.

Original language	English
Pages (from-to)	6728-6740
Number of pages	13
Journal	Journal of Organic Chemistry
Volume	83
Issue number	12
Early online date	29 May 2018
DOIs	https://doi.org/10.1021/acs.joc.8b00392
Publication status	Published - 15 Jun 2018

Keywords

alkenes
organic synthesis
dihydroxylation

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10.1021/acs.joc.8b00392

Alamillo-Ferrer-etal-JOC-2018-Alkene-oxyamination-using-malonoyl-peroxides-preparation-of-pyrrolidinesAccepted author manuscript, 1.14 MB

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title = "Alkene oxyamination using malonoyl peroxides: preparation of pyrrolidines and isoxazolidines",

abstract = "Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.",

keywords = "alkenes, organic synthesis, dihydroxylation",

author = "Carla Alamillo-Ferrer and Curle, {Jonathan M} and Davidson, {Stuart C} and Lucas, {Simon C C} and Atkinson, {Stephen J} and Matthew Campbell and Kennedy, {Alan R} and Tomkinson, {Nicholas C O}",

year = "2018",

month = jun,

day = "15",

doi = "10.1021/acs.joc.8b00392",

language = "English",

volume = "83",

pages = "6728--6740",

journal = "Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society",

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TY - JOUR

T1 - Alkene oxyamination using malonoyl peroxides

T2 - preparation of pyrrolidines and isoxazolidines

AU - Alamillo-Ferrer, Carla

AU - Curle, Jonathan M

AU - Davidson, Stuart C

AU - Lucas, Simon C C

AU - Atkinson, Stephen J

AU - Campbell, Matthew

AU - Kennedy, Alan R

AU - Tomkinson, Nicholas C O

PY - 2018/6/15

Y1 - 2018/6/15

N2 - Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.

AB - Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.

KW - alkenes

KW - organic synthesis

KW - dihydroxylation

U2 - 10.1021/acs.joc.8b00392

DO - 10.1021/acs.joc.8b00392

M3 - Article

C2 - 29812939

SN - 0022-3263

VL - 83

SP - 6728

EP - 6740

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 12

ER -

Alkene oxyamination using malonoyl peroxides: preparation of pyrrolidines and isoxazolidines

Abstract

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