Back to Table of Contents

44762-B1
Asymmetric Catalytic Hydroamination of Aminoallenes and Aminoalkenes by Chiral Titanium Amide-Alkoxide Complexes

Adam R. Johnson, Harvey Mudd College

We have been studying the intramolecular hydroamination of substituted aminoallenes with chiral titanium amino-alcohol derived catalysts.  The ligands are prepared in two steps from natural or unnatural amino acids and are enantiomerically pure.  We performed the hydroamination reaction catalytically with an enhanced regioselectivity for a-vinylpyrrolidine products over other titanium catalysts, with enantiomeric excesses of up to 16% for our first generation ligands (R' = H).  The aims over the last year were to improve upon our initial results through systematic ligand tuning.

Asymmetric intramolecular hydroamination of aminoallenes with titanium amino alcohol complexes;  R* = CH₂Ph or CHMe₂;  R = ⁱPr, c-C₆H₁₁ or 2-adamantyl;  1^st generation ligands, R' = H, Me, Bu or Ph.

Our first goal was to prepare ligands with increased steric bulk (R' = Me, Bu or Ph) by alkylating with the appropriate Grignard reagent instead of reduction with LiAlH₄ during the ligand synthesis.  Except for one derivative that has resisted multiple attempts at synthesis (R = ⁱPr, R* = CHMe₂, R' = Ph), we have completed the series and have synthesized and characterized the remaining 17 ligands. 

The substrates for the hydroamination reaction must be synthesized in a six-step procedure, and we sought a more rapid screen for catalytic activity by investigating the alkylation of benzaldehyde with diethylzinc.  Our ligands and their titanium complexes catalyze this reaction, and since the substrate is commercially available, it is a more rapid screen for enantioselectivity.  When this reaction is carried out with our first generation ligands (R' = H), we observe enantiomeric excesses below 10% in most cases.  However, increasing the steric bulk (R' = Bu or Ph) generally increases the ee values significantly, with values near 75% for our best ligands. 

We then continued our investigation of the catalytic intramolecular hydroamination with an aminoallene substrate.  We used 6-methyl-hepta-4,5-dienylamine as our substrate (as shown in the figure) as it gives only a single product.  Enantioselectivities were measured for the 17 newly prepared ligands;  however, there is not a substantial increase in enantioselectivity with the second generation ligands in this reaction as was seen for the benzaldehyde screen.  This led us to two conclusions.  First, that the benzaldehyde reaction is not a good catalytic screen for the hydroamination.  The second is that we require more substantial ligand tuning to achieve higher enantioselectivity in this reaction.

We have prepared six sulfonamide ligands, including four with electron withdrawing CF₃ groups and have determined the enantioselectivities of the hydroamination reaction with these new ligands at three temperatures.  We were hoping that the increased electron withdrawing character of the sulfonamide ligands would result in an increase in the rate of the reaction.  This would allow us to carry out the reaction at a lower temperature and improve enantioselectivity.  When carried out at 135 °C according to our standard procedure, we observed 100% conversion, but no significant change in enantioselectivity relative to other amino alcohol ligands.  Reducing the temperature to either 110 °C or 95 °C resulted in very low conversion.  The data at the lower temperatures are still preliminary and need to be repeated.

Back to top