Archive for the ‘chirality’ 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.


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


Intermediate II


August 24th

August 24, 2007

I’ll confess that most of the theoretical methods are beyond me, but I found the premise of a recently published paper in Angewandte Int. Ed. intriguing.

Based on experiment and theory David Beratan (Duke University) shows that with certain chiral molecules the solvent directly contributes to the observed Optical Rotation (OR) of the solute.  They propose that the solvent sorrounding the chiral molecule creates a chiral shell, or in their words a “chiral imprint” and as such is capabable to exhibit an OR by itself  if the solvent molecules interact with the polarized light.

If true I think this finding has broader implications since it might be useful in the development of more accurate solvation models. For instance the results are not predicted by continuum solvent models.

Another interesting question is to what extent might the solvent shell contribute to the outcome of stereoselective reactions?