Hydroamination
The hydroamination reaction is the addition an N-H bond across the C=C or C=C of an alkene or alkyne. This is a highly atom economical method of preparing substituted amines that are attractive targets for organic synthesis and the pharmaceutical industry.
Despite substantial effort, the development of a general catalytic process for this reaction remains elusive. Progress has been reported on the hydroamination of alkynes and alkenes using lanthanides and late transition metals. Although there have been many reports of the catalytic hydroamination reaction with group IV metals, there are far fewer describing enantioselective catalysis.
Titanium and zirconium complexes catalyze inter-molecular hydroamination of alkynes and allenes. Both stoichiometric and catalytic variants were initially examined with zirconocene bis(amido) complexes. Titanocene amido and sulfonamido complexes catalyze the intra-molecular hydroamination of aminoalkenes via a [2+2] cycloaddition that forms the corresponding azametallacyclobutane, as illustrated in Figure 1. Subsequent protonolysis by incoming substrate gives the α-vinyl-pyrrolidine (1) or tetrahydropyridine (2) product. There is substantial experimental and theoretical evidence for the proposed imido intermediate and mechanism with neutral group IV catalysts.
References
- Kai C. Hultzsch "Catalytic asymmetric hydroamination of non-activated olefins" (Review) Organic & Biomolecular Chemistry, 2005, 3, 1819-1824. doi:10.1039/b418521h
- Hartwig, J. F. Development of catalysts for the hydroamination of olefins. Pure Appl. Chem. 2004, 76, 507-516.
- Odom, A. L. "New C–N and C–C bond forming reactions catalyzed by titanium complexes" Dalton Trans., 2005, (2),225-233. doi:10.1039/b415701j
- Shi, Y.; Hall, C.; Ciszewski, J. T.; Cao, C.; Odom, A.L. "Titanium dipyrrolylmethane derivatives: rapid intermolecular alkyne hydroamination" Chem. Commun., 2003, (5),586-587. doi:10.1039/b212423h