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Organic Catalysts Get Better and Better |
by John
Emsley
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WHAT'S
HOT IN CHEMISTRY |
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Rank |
Paper |
Citations
This Period (Jan-
Feb 07) |
Rank
Last Period (Nov-Dec 06) |
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1 |
A.J.A. Cobb, et al., "Organocatalysis with proline derivatives: improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions," Org. & Biomolec. Chem.,
3(1): 84-96, 7 January 2005. [U. Cambridge, U.K.] *879SC |
17 |
† |
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2 |
X. Wang, et al., "A general strategy for
nanocrystal synthesis," Nature, 437(7055): 121-4, 1 September 2005. [Tsinghua University, Beijing, China; Natl. Ctr. Nanosci.
& Nanotech., Beijing] *960AC |
16 |
2 |
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3 |
Y. Hayashi, et al., "Diphenylprolinol silyl ethers as efficient organocatalysts for the asymmetric Michael reaction of aldehydes and nitroalkenes," Angew. Chem. Int. Ed., 44(27): 4212-5, 4 July 2005. [Tokyo U. Sci.,
Japan] *943LC |
16 |
† |
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4 |
D. Enders, et al., "Control of four stereocentres in a triple cascade organocatalytic reaction," Nature, 441(7095): 861-3, 15 June 2006. [Aachen
U., Germany] *052SL |
16 |
† |
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5 |
M. Law, et al., "Nanowire dye-sensitized
solar cells," Nature Materials,
4(6): 455-9, June 2005. [U. Calif., Berkeley; Lawrence Berkeley Natl. Lab.,
CA] *931RL |
15 |
† |
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6 |
Y. Huang, et al., "Enantioselective organo-cascade catalysis," J. Am. Chem. Soc.,
127(43): 15051-3, 2 November 2005. [Caltech, Pasadena] *979HV |
15 |
† |
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7 |
N. Mase, et al., "Organocatalytic direct Michael reaction of ketones and aldehydes with BETA-nitrostyrene in brine," J. Am. Chem. Soc., 128(15): 4966-7, 19 April 2006. [Shizuoka U., Hamamatsu,
Japan; Scripps Res. Inst., La Jolla, CA] *034GN |
13 |
† |
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8 |
Z.L. Wang, J. Song, "Piezoelectric nanogenerators based on zinc oxide nanowire arrays," Science,
312(5771): 242-6, 14 April 2006. [Georgia Inst. Tech., Atlanta; Peking U.,
Beijing, China] *032HK |
12 |
† |
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9 |
J. Xiang, et al., "Ge/Si nanowire heterostructures as high-performance field-effect transistors," Nature,
441(7092): 489-93, 25 May 2006. [Harvard U., Cambridge, MA] *045YP |
12 |
† |
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10 |
P.X. Gao, et al., "Conversion of zinc oxide nanobelts into superlattice-structured nanohelices," Science, 309(5741): 1700-4, 9 September 2005. [Georgia Inst. Tech., Atlanta; Peking U., China; Natl. Ctr. Nanosci.
& Nanotech., Beijing, China] *963WK |
11 |
† |
SOURCE:
Thomson Scientific's Hot
Papers Database.
Read
the Legend. |
 he ability of the amino acid proline not only to catalyze organic reactions but to favor a particular enantiomer was first noted more than 30 years ago. It excited little interest. Proline’s potential was rediscovered around seven years ago, and now there is a flourishing field of so-called organocatalysis.
Proline is somewhat limited as a catalyst. It is a highly polar molecule, which means it needs highly polar solvents, such as water or methanol, and clearly these limit its use by being non-compatible with reactants or reaction products. Organic chemists have sought ways to surmount this difficulty, and Steve Ley and his group in the Department of Chemistry at the University of Cambridge, have succeeded brilliantly. Their findings are reported in paper #1. This describes three types of modified proline, each with an alternative group in place of its polar carboxylic acid group. One variant has a tetrazole ring, and the other two have either a methyl, or phenyl, acyl sulfonamide group. The rationale behind these modifications was to retain an acidic proton in the group while
increasing the solubility in a wider range of solvents.
Having designed these alternative proline compounds, Ley then used them on three types of reaction widely used in organic synthesis: the asymmetric Mannich reaction, the nitro-Michael reaction, and the aldol reaction. In all cases the new catalysts outperformed proline.
For example, the Mannich reaction between cyclohexanone and an imino ethyl glyoxalate was performed in dichloromethane as the non-polar solvent. The addition of 5% proline catalyst resulted in no product being formed after two hours, whereas the addition of a similar amount of the tetrazole catalyst gave a yield of product after two hours of 65% and it was overwhelmingly a single enantiomer (>99%). Equally interesting was that reducing the amount of catalyst to 1%—and more in keeping with what one expects for a catalyst—the reaction still gave a high yield, albeit taking 16 hours, and again the product was the single enantiomer. The sulfonamide catalysts performed equally well, the phenyl version giving excellent and equally selective yields in dichloromethane, methanol, dimethyl sulfoxide, and tetrahydrofuran. In this case the amount of catalyst was increased to 20%.
The other studied reactions gave more variable yields and selectivities. These reactions were the nitro-Michael reaction of cyclohexanone and
β-nitrostyrene, and the asymmetric aldol reaction where a range of ketones were studied. Excellent enantioselectivities were observed for straight chain ketones, but cyclic ketones gave less impressive results.
More recently Ley has used the tetrazole catalyst for the conjugative addition of malonates to enones (K.R. Knudsen,
et al., Chem. Commun., 1: 66-8, 2006) and of nitroalkanes to enones (C.E.T. Mitchell,
et al., Chem. Commun., 42: 5346-8, 2005), again with excellent results. Other syntheses using the catalysts reported in paper #1 have been the formation of chiral 3,6-dihydropyridazines from aldehydes (A.J. Oelke,
et al., Synlett, 16: 2548-52; 2006) and the conjugate addition of nitroalkanes to unsaturated cyclic and acyclic systems (C.E.T. Mitchell,
et al., Org. Biomol. Chem., 4[10]: 2039-49; 2006).
Paper #1 is not the only paper on the list dealing with organocatalysis. Paper #3 comes from the laboratory of Yujiro Hayashi of Tokyo University and reports on the asymmetric Michael reaction of aldehydes and nitroalkenes catalyzed by a trimethylsilyl derivative of diphenyl-2-pyrrolidonemethanol. The catalyst loading was 10-20%, yields were in the range 70-85%, and enantiomeric selectivity was 99%. Hayashi even speculated on a possible transition state for the catalyst and the nitroalkene.
Why is organocatalysis generating so much interest? For decades the best catalysts for organic reactions have been metal based, and this made sense in that reacting molecules would orientate themselves as ligands and so be brought near together. Clearly organic molecules must also be able to bring reacting molecules into close proximity with one another. As the subject develops, we might well see more exciting catalysts being discovered. Maybe one day there will be direct evidence of exactly how they work their magic.
Until then, all we can do is wait for the next remarkable paper. 
Dr. John Emsley is based at the Department of
Chemistry,
Cambridge University, U.K.
Science
Watch®, July/August 2007, Vol. 18, No. 4
Citing URL:
http://www.sciencewatch.com/july-aug2007/sw_july-aug2007_page7.htm |
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