Archive for the ‘enantiomer’ Category

December 9, 2007

ts2.pngI have carried out simplified analysis of some recent papers on organocatalysis. The first example comes from a paper from the Jacobsen group (Raheem et al. J. Am. Chem. Soc. 2007, 13404, 10.1021/ja076179w) which describes a “H-bond donor” catalyst that effects an enantioselective Pictect-Spengler type reaction. Jacobsen attributes the selectivity to the substrate-halide-catalyst complex shown on the left. However, leaving the halide out of the complex yields an ion pair or perhaps a covalently bound intermediate as shown on the right. This brings the catalyst and substrate into closer contact than the halide-containing complex.

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A ground-state model of the des-halide intermediate appears to work in explaining the enantioselectivity of the reaction as shown in the pictures below. In intermediate I, which leads to the minor enantiomer, the indole ring is not able to cyclize onto the acyliminium ion since it is being blocked by an appendage projecting from the catalyst. In contrast when the catalyst is bound to the other face of the acyliminium ion, as in intermediate II, the indole is free to cyclize which leads to the observed dominant enantiomer. Although Jacobsen indicates that some of their experimental work on the mechanism of catalysis makes the direct interaction of the catalyst with the acyliminium less likely, this intermediate is consistent, at least qualitatively, with the stereoselectivity reported for the paper. I am eager to see more details concerning the mechanism to see if this my interpretation holds up.

Intermediate I

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Intermediate II

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Word of the week…Racemate

March 29, 2007

The definition of racemate, an equimolar mixture of enantiomers, is old hat to most of us having learned it in our introductory organic chemistry courses. And so it was for me until recently.

Being a synthetic chemist, I don’t have much time or energy to gain a deep understanding of physicochemical properties. Therefore, I was not surprised to find that I was ignorant of the fact that in the solid state racemates come in two flavors and that the IUPAC has developed specefic nomenclature to define each. There is a “racemic compound” where the two enantiomers are co-crystallized homogenously into a single crystal. However, racemates can also exist as “racemic conglomerates” which describes the situation where the two enantiomers crystallize separately but still might be occluded in a single particle.

Tangentially related to this topic is Wallach’s rule which states that racemic crystals (ie. racemic compounds) are more dense than the crystals of the pure enantiomers. Which makes me think…since increased crystalline density is generally associated with increased stability and increased crystalline stability can be correlated with reduced aqueous solubility, one would expect that racemates would be less soluble than their pure enantiomers. I did a search of the literature see if this was the case and come up with the examples below..there appears to be a  slight trend.

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