Hydroxy-Group Directivity in the Nitroso Ene Reaction:  Diastereo- and Regioselective Amination of Chiral Allylic Alcohols

Photooxygenation involving the first excited singlet state of molecular oxygen is a versatile method for the generation of a multitude of oxy-functionalized target molecules often with high regio- and stereoselectivities. The efficiency of singlet-oxygen reactions is largely dependent on the nonradiative deactivation paths, mainly induced by the solvent and the substrate intrinsically. The intrinsic (physical) quenching properties as well as the selectivity-determining factors of the (chemical) quenching can be modified by adjusting the microenvironment of the reactive substrate. Tetraarylporphyrins or protoporphyrin IX were embedded in polystyrene (PS) beads and in polymer films or covalently linked into PS during emulsion polymerization. These polymer matrices are suitable for a broad variety of (solvent-free) photooxygenation reactions. One specific example discussed in detail is the ene reaction of singlet oxygen with chiral allylic alcohols yielding unsaturated β-hydroperoxy alcohols in (threo) diastereoselectivities, which depended on the polarity and hydrogen-bonding capacity of the polymer matrix. These products were applied for the synthesis of mono- and spirobicyclic 1,2,4-trioxanes, molecules that showed moderate to high antimalarial properties. Subsequent structure optimization resulted in in vitro activities that surpassed that of the naturally occurring sesquiterpene-peroxide artemisinin.

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Hydroxy-directed diastereoselective ene reaction of triazolinediones with chiral allylic alcohols

Tetrahedron Letters ◽

10.1016/s0040-4039(98)00222-6 ◽

1998 ◽

Vol 39 (17) ◽

pp. 2625-2628 ◽

Cited By ~ 5

Author(s):

Waldemar Adam ◽

Bernd Nestler ◽

Aurelia Pastor ◽

Thomas Wirth

Keyword(s):

Allylic Alcohols ◽

Ene Reaction

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ChemInform Abstract: μ-OXO-BIS(CHLOROTRIPHENYLBISMUTH): A MILD REAGENT FOR THE OXIDATION OF THE HYDROXY GROUP, ESPECIALLY IN ALLYLIC ALCOHOLS

Chemischer Informationsdienst ◽

10.1002/chin.197917159 ◽

1979 ◽

Vol 10 (17) ◽

Author(s):

D. H. R. BARTON ◽

J. P. KITCHIN ◽

W. B. MOTHERWELL

Keyword(s):

Hydroxy Group ◽

Allylic Alcohols

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ChemInform Abstract: Solvent Effects in the Stereoselectivity of the Ene Reaction of Singlet Oxygen with Allylic Alcohols.

ChemInform ◽

10.1002/chin.199701095 ◽

2010 ◽

Vol 28 (1) ◽

pp. no-no

Author(s):

M. STRATAKIS ◽

M. ORFANOPOULOS ◽

C. S. FOOTE

Keyword(s):

Singlet Oxygen ◽

Solvent Effects ◽

Allylic Alcohols ◽

Ene Reaction

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ChemInform Abstract: Hydroxy-Directed Diastereoselective Ene Reaction of Triazolinediones with Chiral Allylic Alcohols.

ChemInform ◽

10.1002/chin.199830144 ◽

2010 ◽

Vol 29 (30) ◽

pp. no-no

Author(s):

W. ADAM ◽

B. NESTLER ◽

A. PASTOR ◽

T. WIRTH

Keyword(s):

Allylic Alcohols ◽

Ene Reaction

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Synthesis of spiroannulated and 3-arylated 1,2,4-trioxanes from mesitylol and methyl 4-hydroxytiglate by photooxygenation and peroxyacetalization

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.6.61 ◽

2010 ◽

Vol 6 ◽

Cited By ~ 5

Author(s):

Axel G Griesbeck ◽

Lars-Oliver Höinck ◽

Jörg M Neudörfl

Keyword(s):

Singlet Oxygen ◽

Lewis Acid ◽

Allylic Alcohols ◽

Ene Reaction ◽

X Ray ◽

X Ray Crystallography ◽

Homoallylic Alcohols ◽

Acid Catalyzed ◽

Benzaldehyde Derivatives

Cycloalkanones were utilized in the Lewis acid catalyzed peroxyacetalization of ß-hydroperoxy homoallylic alcohols (prepared by the ene reaction of the allylic alcohols mesitylol and methyl 4-hydroxytiglate, respectively, with singlet oxygen) to give spiroannulated 1,2,4-trioxanes 5a–5e and 9a–9e, respectively. A second series of 3-arylated trioxanes 10a–10h, that are available from the hydroperoxy alcohol 4 and benzaldehyde derivatives, was investigated by X-ray crystallography.

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