Hydroamination

From Wikipedia, the free encyclopedia

The hydroamination reaction is the addition of an N-H bond across the C=C or C≡C bonds 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 [1] [2] [3] [4] [5].

The hydroamination reaction is approximately thermodynamically neutral; there is a high activation barrier due to the repulsion of the electron-rich substrate and the amine nucleophile. The reaction also has a high negative entropy, making it unfavorable at high temperatures. As a result, catalysts are necessary for this reaction to proceed.[6] [7]

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.

Figure 1. The catalytic hydroamination of aminoallenes to form chiral α-vinyl-pyrrolidine (1) and tetrahydropyridine (2) products. L2 = Cp2 or bis(amide).
Figure 1. The catalytic hydroamination of aminoallenes to form chiral α-vinyl-pyrrolidine (1) and tetrahydropyridine (2) products. L2 = Cp2 or bis(amide).

[edit] References

  1. ^ Kai C. Hultzsch (2005). "Catalytic asymmetric hydroamination of non-activated olefins" (Review). Organic & Biomolecular Chemistry 3: 1819–1824. doi:10.1039/b418521h. 
  2. ^ Hartwig, J. F. (2004). "Development of catalysts for the hydroamination of olefins". Pure Appl. Chem. 76: 507–516. doi:10.1351/pac200476030507. 
  3. ^ Shi, Y. H.; Hall, C.; Ciszewski, J. T.; Cao, C. S.; Odom, A. L. (2003). "Titanium dipyrrolylmethane derivatives: rapid intermolecular alkyne hydroamination". Chemical Communications 5: 586–587. doi:10.1039/b212423h. 
  4. ^ Pohlki, F., Doye, S. (2003). "The catalytic hydroamination of alkynes". Chemical Society Reviews 32: 104–114. doi:10.1039/b200386b. 
  5. ^ Odom, A. L. (2005). "New C–N and C–C bond forming reactions catalyzed by titanium complexes". Dalton Trans. 2: 225–233. doi:10.1039/b415701j. 
  6. ^ Müller, T. E. Beller, M. (1998). "Metal-Initiated Amination of Alkenes and Alkynes". Chemical Reviews 98 (2): 675–704. doi:10.1021/cr960433d. 
  7. ^ M. Beller, J. Seayad, A. Tillack and H. Jiao (2004). "Catalytic Markovnikov and anti-Markovnikov Functionalization of Alkenes and Alkynes: Recent Developments and Trends". Angewandte Chemie, International Edition 43 (26): 3368–3398. doi:10.1002/anie.200300616.