title: Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine.
abstract: Three chiral diamines were synthesised and evaluated as sparteine surrogates in the lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis and attempted resolution of sparteine-like diamines [(1S*,2R*,8R*)-10-methyl-6,10-diazatricyclo[6.3.1.0(2,6)]dodecane and (1S*,2R*,9R*)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane] (via inclusion complex formation) are reported. Unfortunately, it was only possible to resolve the diazatricyclo[7.3.1.0(2,7)]tridecane compound. An alternative route to (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane starting from the natural product, (-)-cytisine, is described. This simple three-step route furnished gram-quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate in the route, (1R,5S,12S)-3-methoxycarbonyldecahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic diamines described in this paper to be unequivocally established. Two other diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were prepared using standard methods. These diamines lacked the bispidine framework of (-)-sparteine and were found to impart vastly inferior enantioselectivity. It was concluded that, for the asymmetric lithiation substitution of N-Boc pyrrolidine, a rigid bispidine framework and only three of the four rings of (-)-sparteine are needed for high enantioselectivity. Furthermore, it is shown that diamine (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane is the first successful (+)-sparteine surrogate.
authors.affiliation: Department of Chemistry, University of York, Heslington, York, UK YO10 5DD.
authors.forename: Jean-Paul R
authors.initials: JP
authors.lastname: Hermet
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dearden
authors.forename: Justin R
authors.initials: JR
authors.lastname: Harrison
authors.forename: Tobias
authors.initials: T
authors.lastname: Koplin
authors.forename: Peter
authors.initials: P
authors.lastname: O'Brien
authors.forename: Jérôme
authors.initials: J
authors.lastname: Parmene
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tyurin
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Whitwood
authors.forename: John
authors.initials: J
authors.lastname: Gilday
authors.forename: Neil M
authors.initials: NM
authors.lastname: Smith