770735-40-5Relevant academic research and scientific papers
Intramolecular hydroamination of trisubstituted aminoallenes catalyzed by titanium complexes of diaryl substituted tridentate imine-diols
Fok, Emily Y.,Show, Veronica L.,Johnson, Adam R.
, (2021)
Our laboratory has developed catalysts based on earth abundant titanium for asymmetric reactions including intramolecular hydroamination. Previously, we showed that titanium complexes of imine diol ligands showed improved enantioselectivity relative to complexes with bidentate amino alcohol ligands. As the catalyst with the highest selectivity had di-tert-butyl substitution, we sought to increase the steric protection by preparing three new ligands with diaryl substitution. These ligands were readily prepared in two steps: first, synthesis of diaryl substituted salicylaldehydes by a Suzuki coupling and second, a Schiff base condensation with a chiral amino alcohol. After characterizing the ligands, in situ hydroamination/cyclization with 6-methyl-hepta-4,5-dienylamine was carried out at temperatures ranging from 105 °C to 135 °C to give exclusively 2-(2-methyl-propenyl)-pyrrolidine with enantioselectivity up to 22 %ee. Unexpected dimerization of the catalyst resulted in reduced activity, so the reaction required a catalyst loading of 10–20%.
Catalytic intramolecular hydroamination of aminoallenes using titanium and tantalum complexes of sterically encumbered chiral sulfonamides
Johnson, Adam R.,Porter, Hanna Z.,Sha, Fanrui,Shimizu, Emily A.,Slocumb, Hannah S.,Takase, Michael K.,Towell, Sydney E.,Zhen, Yi
, p. 12418 - 12431 (2020/10/02)
Catalysis using earth abundant metals is an important goal due to the relative scarcity and expense of precious metal catalysts. It would be even more beneficial to use earth abundant catalysts for the synthesis of common pharmaceutical structural motifs such as pyrrolidine and pyridine. Thus, developing titanium catalysts for asymmetric ring closing hydroamination is a valuable goal. In this work, four sterically encumbered chiral sulfonamides derived from naturally occurring amino acids were prepared. These compounds undergo protonolysis reactions with Ti(NMe2)4 or Ta(NMe2)5 to give monomeric complexes as determined by both DOSY NMR and X-ray crystallography. The resulting complexes are active for the ring closing hydroamination hepta-4,5-dienylamine to give a mixture of tetrahydropyridine and pyrrolidine products. However, the titanium complexes convert 6-methylhepta-4,5-dienylamine exclusively to 2-(2-methylpropenyl)pyrrolidine in higher enantioselectivity than those previously reported, with enantiomeric excesses ranging from 18-24%. The corresponding tantalum complexes were more selective with enantiomeric excesses ranging from 33-39%.
Asymmetric catalytic intramolecular hydroamination of aminoallenes by tantalum amidoalkoxide complexes
Hansen, Michelle C.,Heusser, Carolyn A.,Narayan, Tarun C.,Fong, Kristine E.,Hara, Nagiko,Kohn, Alexander W.,Venning, Alexander R.,Rheingold, Arnold L.,Johnson, Adam R.
experimental part, p. 4616 - 4623 (2011/12/03)
A series of tantalum complexes of chiral bidentate amidoalkoxide ligands was prepared. The crystal structure of one complex, Ta(NMe2) 3[-OCPh2CH(CHMe2)N(c-C6H 11)-] was obtained. Unlike previously described titanium complexes with these ligands, which are dimeric with bridging oxygen atoms, this tantalum complex is monomeric with an approximate trigonal-bipyramidal geometry. The resulting complexes were examined for their in situ activity for catalytic asymmetric hydroamination/cyclization of an aminoallene. Enantioselectivities up to 80% ee were observed for the cyclization of 6-methylhepta-4,5-dienylamine to 2-(2-methylpropenyl)pyrrolidine at 135 °C with 5 mol % catalyst loading.
