A Bifunctional Cyclopropeneimine with a Tunable Hydrogen-Bond Donating Group and Its Application in the Enantioselective Synthesis of α,β-Diamino Phosphonates

Lambert and co-workers have developed several chiral bases using a cyclopropeneimine as the basic moiety. Typically, these catalysts have a pendant hydroxyl group which acts as a hydrogen-bond donor and activates the electrophile. In catalysts with a hydrogen-bond donor, prior work from the Sigman group has shown that the acidity of the donor plays an important role in imparting selectivity. However, in the case of cyclopropeneimines reported by Lambert and co-workers, the acidity of the pendant arm is not easily tunable. To address this, we have developed a cyclopropeneimine catalyst with cyclohexanediamine as the chiral scaffold. One of the amino groups on the cyclohexanediamine is part of the cyclopropeneimine moiety, while the other is functionalized with an acyl group. The acidity of the pendant NH group was varied by changing the acyl group. We probed the utility of this catalyst in an enantioselective synthesis of α,β-diamino phosphonates using N-carbamoyl imines and fluorenone-imine phosphonates as the substrates. By varying the acyl group on the catalyst, we were able to optimize the enantioselectivity of the reaction. Using this approach, an enantiomer ratio of 92.5:7.5 was obtained with a 1-naphthyl derived imine. In general, imines with an electron-deficient aromatic group gave higher selectivities. Additionally, the optimized catalyst has good long-term stability in solution.