Synlett 2009(15): 2412-2416  
DOI: 10.1055/s-0029-1217734
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Thieme Chemistry Journal Awardees - Where Are They Now? Aldol Synthesis by anti-Markovnikov Hydration of Propargyloxy Substrates: Feasibility, Stereospecifity, and Reiterative Alkynylation-Hydration

Lukas Hintermann*, Thomas Kribber, Aurélie Labonne, Eva Paciok
Institut für Organische Chemie, RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany
Fax: +49(241)8092391; e-Mail: lukas.hintermann@oc.rwth-aachen.de;
Further Information

Publication History

Received 5 June 2009
Publication Date:
27 August 2009 (online)

Abstract

Aldol derivatives have been synthesized by redox-neutral catalytic anti-Markovnikov hydration of propargyloxy substrates. A reiterative sequence of aldehyde alkynylation and alkyne hydration leads to 1,3-polyol derivatives.

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The idea of synthesizing aldols in this way has been expressed by others, see ref. 8b and ref. 14.

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Hydration experiments with IndRuCl(PPh3)2 were attempted in either i-PrOH-H2O or an aqueous micellar system, with several alkynes. GC-MS analysis usually revealed the presence of starting alkyne. Among minor reaction products, we found traces of 2-octanone and heptene (from 1-octyne), and products of alkyne trimerization. In addition, decomposition of the ruthenium complex to indene and Ph3P was observed and tenside decomposition products (dodecanol, dodecene, chlorododecane from sodium dodecyl sulfate).

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See the Supporting Information for experimental details and additional information.

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Catalyst loadings of 3 mol% gave conversions of only
20-30%.

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A solvent screen had indicated the superiority of acetone over i-PrOH, EtOH, MeOH, and THF.

26

See the Supporting Information for experimental data.

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These conditions are characterized by use of the reaction medium acetone-H2O (4:1) and will be discussed elsewhere.

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The Supporting Information to this article contains experiment descriptions, analytical data, and additional information.