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

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.

Key words

addition reactions - aldehydes - alkynes - homogeneous catalysis - ruthenium

References and Notes

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11

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

15

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).

17

See the Supporting Information for experimental details and additional information.

24

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

25

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

26

See the Supporting Information for experimental data.

32

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

34

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