The treatment of unsaturated amines with electrophiles presents issues with chemoselectivity as the nitrogen lone pair and the olefinic bond are both potential sites for reaction. We have developed a range of methodologies to combat this problem and developed several stereoselective processes, such as the ring-closing iodoamination methodology described below, that have proven useful in total synthesis.
Treatment of a range of unsaturated β-amino esters (containing a cis-dioxolane unit) with iodine promotes a novel ring-closing alkene iodoamination reaction which proceeds with concomitant N-debenzylation, providing a simple and stereoselective route to iodomethyl pyrrolidines. Functional group interconversion of the resulting iodomethyl pyrrolidines upon treatment with AgOAc proceeds via the corresponding aziridinium ion, with subsequent deprotection giving access to polyhydroxylated pyrrolidines.
- Asymmetric syntheses of (–)-ADMJ and (+)-ADANJ: 2-deoxy-2-amino analogues of
(–)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin
Davies, S. G.; Figuccia A. L. A.; Fletcher, A. M.; Roberts, P. M.; Thomson, J. E. J. Org. Chem. 2016,
81, 6481 [View Journal Page]
- Asymmetric synthesis of the tropane alkaloid (+)-pseudococaine via ring-closing iodoamination
Brock, E. A.; Davies, S. G.; Lee, J. A.; Roberts, P. M.; Thomson, J. E. Org. Lett. 2012, 14, 4278
[View Journal Page]
- Ring-closing iodoamination of homoallylic amines for the synthesis of polysubstituted pyrrolidines: application to the asymmetric synthesis of (–)-codonopsinine
Davies, S. G.; Lee, J. A.; Roberts, P. M.; Thomson, J. E.; West, C. J. Tetrahedron 2012, 68, 4302
[View Journal Page]
- Iodine-mediated ring closing iodoamination with concomitant N-debenzylation for the asymmetric synthesis of polyhydroxylated pyrrolidines
Davies, S. G.; Nicholson, R. L.; Price, P. D.; Roberts, P. M.; Russell, A. J.; Savory, E. D.; Smith, A. D.; Thomson, J. E. Tetrahedron: Asymmetry 2009, 20, 758 [View Journal Page]