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| Research - Nucleophilic Catalysis | |||||
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DMAP (dimethylaminopyridine) 1 is a ubiquitous nucleophilic catalyst that is used to accelerate many common organic transformations. Recently several chiral DMAP equivalents such as 2 and 3 have been reported that enable reactions, such as the kinetic resolution of 4, to be carried out with a high selectivity factor S. However neither these or other the chiral DMAP equivalents are especially accessible (the generation of 2 is complex, and both of these systems require resolution techniques such as semi-preparative HPLC). |
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Our approach to this
problem avoids the issue of catalyst resolution by incorporating readily
available sources of chirality into heterocycles where the asymmetric
environment of the nucleophilic nitrogen (N)
is controlled by attachment to a bulky cobalt metallocene. The basis of
this approach was first demonstrated with imidazole 5,
for which the conformer revealed in the X-ray crystal structure is also
dominant in solution, placing this heterocycle in an environment of virtual
planar chirality. [1]
X-ray
crystal structure of 5 (R = t-Bu).This approach has been
extended to DMAP itself, with the synthesis of cobalt metallocene appended
derivatives 6 and 7 of which the latter
is especially effective as a nucleophilic catalyst. The incorporation
of C2-symmetic pyrrolidines into related structures and the application
of these as catalysts in asymmetric synthesis will be reported shortly.
[2]
X-ray
crystal structure of 7.[1]
G. Jones and C. J. Richards, Organometallics, 2001, 20,
1251. [2] D. C. D. Butler, H. V. Nguyen and C. J. Richards, in preparation.