Michael G.
Edwards
a,
Rodolphe F. R.
Jazzar
a,
Belinda M.
Paine
a,
Duncan J.
Shermer
a,
Michael K.
Whittlesey
*a,
Jonathan M. J.
Williams
*a and
Dean D.
Edney
b
aDepartment of Chemistry, University of Bath, Claverton Down, Bath, UK BA2 7AY. E-mail: chsmkw@bath.ac.uk; chsjmjw@bath.ac.uk
bGlaxoSmithKline Research & Development, Old Powder Mills, Tonbridge, Kent, UK TN11 9AN
First published on 18th November 2003
Ruthenium complexes have been shown to perform efficient transfer hydrogenation reactions between alcohols and alkenes; in combination with an in situ Wittig reaction, indirect formation of C–C bonds has been achieved from alcohols.
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Scheme 1 Catalytic electronic activation: indirect Wittig reaction upon alcohols. |
Our previous attempts at achieving this reaction using an iridium-based system required heating at 150 °C for 72 h.2 Herein we report on a ruthenium-catalysed approach requiring milder reaction conditions. The use of a ruthenium N-heterocyclic carbene complex allows the reaction to be carried out at significantly lower temperatures and reaction times. We have recently reported the facile C–H bond activation of the N-heterocyclic carbene 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) in Ru(IMes)(PPh3)2(CO)H2 (1) at room temperature in the presence of a sacrificial alkene (Scheme 2).4 The C–H cleavage product 2 readily reforms the starting dihydride upon reaction with H2. The rapid hydrogenation of alkenes5 and the reversibility of the pathway illustrated in Scheme 2 prompted us to investigate the suitability of alcohols as hydrogen donors in this process.6
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Scheme 2 Reversible dehydrogenation/hydrogenation pathway of complex 1. |
It was subsequently demonstrated that vinyltrimethylsilane (3) could be completely hydrogenated by complex 1 at 70 °C to provide ethyltrimethylsilane (4) with isopropanol acting as the hydrogen donor (Scheme 3). Indeed, the crossover transfer hydrogenation7 reaction between one equivalent of alcohol and one equivalent of alkene could also be readily achieved (Scheme 3). (±)-Phenethyl alcohol (6) and tert-butyl cinnamate (5) were converted solely into acetophenone (8) and tert-butyl dihydrocinnamate (7) using 5 mol% of complex 1.
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Scheme 3 Transfer hydrogenation reactions with complex 1. |
The ability to effect a crossover transfer hydrogenation is critical to the success of the indirect Wittig reaction identified in Scheme 1. In the absence of crossover hydrogenation the cycle is unable to proceed once the initial catalyst has been exhausted. Following the success of these transfer hydrogenation reactions the catalytic activity of complex 1 in the indirect Wittig process was examined (Scheme 4, Table 1). Table 1 shows the performance of complex 1 (5 mol% loading) for reaction of benzyl alcohol (9) with the ester ylide (10) in toluene solution at 80 °C. In all cases 5 mol% of vinyltrimethylsilane (3) was added to accomplish the initial dehydrogenation of the catalyst required for the reaction to proceed. The reaction catalysed by complex 1 afforded 90% of the dihydrocinnamate product (11) after 24 hours (entry 1). The complex Ru(PPh3)3(CO)H2 also proved to be successful in the indirect Wittig reaction, although it proved to be inferior to complex 1 over the same reaction period (entry 2).8
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Scheme 4 Ruthenium catalysed indirect Wittig reactions with benzyl ester ylide 10. |
Entry | Precursor (5 mol%) | Ligand (mol%) | Conversion (%)b |
---|---|---|---|
a The reactions were carried out on a 0.5 mmol scale in toluene (1.5 mL) at 80 °C for 24 hours using 1.1 equivalents of ylide 10. b Determined by 1H NMR spectroscopy. c The precursor and IMes were heated at 70 °C for 1.5 hours in toluene before addition of the remaining reagents. | |||
1 | 1 | — | 90 |
2 | Ru(PPh3)3(CO)H2 | — | 80 |
3 | Ru(PPh3)3(CO)H2 | IMes (5) | 87 |
4c | Ru(PPh3)3(CO)H2 | IMes (5) | 86 |
The highest levels of activity of complex 1 are associated with isolated material; however in situ generation of the catalyst proved to be successful (entries 3 and 4). Thus, whilst the carbene complex 1 is the most successful catalyst, commercially available complex Ru(PPh3)3(CO)H2 was also reasonably effective.
We further demonstrated that the indirect Wittig reaction catalysed by 1 could be successfully achieved in high yield by the use of alternative phosphorane ester ylides with other alcohol substrates (Scheme 5). Using optimised reaction conditions (1 mol% 1, 1.00 M concentration, 80 °C) the indirect Wittig adducts 11, 12, 13, 15 and 17 were obtained in good to excellent isolated yields following column chromatography (70–84%). These results demonstrate that complex 1 displays high catalytic activity for C–C bond formation via this route at moderately low temperatures (80 °C). In contrast, the previously reported2 iridium catalysed reactions afforded indirect Wittig adducts in lower yield, 47–71%, even under extremely forcing reaction conditions (150 °C, 72 hours) and at considerably higher catalyst loadings (5 mol%). In addition, the results indicate that the presence of an N-heterocyclic carbene ligand is beneficial for improved reactivity in comparison with other complexes.
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Scheme 5 Synthesis of indirect Wittig reaction adducts (1 mol%
1, 1.1 equiv. Ph3P![]() ![]() |
In conclusion, we have demonstrated that ruthenium complexes act as catalysts for the formation of C–C bonds from alcohol substrates via an intriguing indirect Wittig reaction.
We thank the EPSRC, GlaxoSmithKline and the University of Bath for financial support and Johnson Matthey plc for the loan of ruthenium trichloride.
Footnote |
† Electronic Supplementary Information (ESI) available: Experimental procedures and characterization data for compounds 1, 11, 12, 13, 15 and 17 along with general experimental procedures. See http://www.rsc.org/suppdata/cc/b3/b312162c/ |
This journal is © The Royal Society of Chemistry 2004 |