Design And Synthesis Of Novel Sulfamide-Amine Alcohols And Their Applications In Asymmetric Catalysis

Herein, using grafting strategy we have developed a new kind of sulfamide-amine alcohol (SAA) ligands by grafting a activator (sulfonamide fragment) to the traditional aminoalcohols, which led to more rigid tridentate coordination model and benefit to the control of chiral surrounding. In this way, the novel chiral SAA ligands possible show good performance in the asymmetric catalysis.We have successfully synthesized SAA ligands from the commercially available (-)-ephedrine, (+)-pseudoephedrine and L-prolinol as the chiral sources. The yields are high and the purifications need not troublesome column chromatography, but simple recrystallization. All of the chiral ligands are stable in air for several months.SAA ligands Lh and ligand Ll were employed into asymmetric addition of diethylzinc to aldehydes in the absence of Ti(O~iPr)4 could induce the products with two opposite absolute configurations. At the room temperature, they could catalyze asymmetric additions of diethylzinc to various substrates including aromatic, aliphatic and α,β-unsaturated aldehydes in high yields (up to 99%) and excellent enantioselectivities (both enantiomers up to >99%ee). This is the first example of using chiral sulfonamide ligands for highly asymmetric addition reaction without addition of Ti(O~iPr)4. On the other hand, in the catalytic system using some SAA ligands such as ligand Lc and Ld, addition of Ti(O~iPr)4 could lead to the reversal of configuration of products. This is till now the first reportthat not changing the backbones of chiral ligands but adding Ti(O~iPr)4 could change the absolute configuration of the product in this reaction.SAA ligand Lh could induce asymmetric addition of terminal alkyne to aldehydes without using air-sensitive Ti(O~iPr)4and expensive Zn(OTf)2.with good result of high yield (up to 99%) and good enantioselectivities (up to 84%ee). To aromatic aldehydes or aliphatic aldehydes, our chiral ligand Lh showed better performance than (-)-N-methylephedrine which had similar structure under the same conditions. This fully showed that its' weakly coordinative sulfonamide moiety of the ligand Lh played an important role for further favorable stereocontrol in the alkynylation. In the catalytic system using chiral ligand 16 addition of Ti(O~iPr)4 could lead to the reversal of stereochemistry, while the system using ordinary SAA ligands could not. To the bulky SAA ligand 17, we not only see the similar phenomenon as ligand 16 but realized that a simple change of the substitutent of the backbone in the ligand could lead to the reversal of configuration of the product.SAA ligand Lg could catalyze asymmetric addition of phenylacetylene to unactivated aromatic ketones in high yields (up to 83%) and high enantioslectivities (up to 83%ee).Chiral N,O ligands were firstly used into the asymmetric transfer hydrogenation of prochiral ketones performed in water. (-)-Ephedrine hydrochloride can induce the reactions in the air with high conversions (up to >99%) and high enantioselectivities (up to 83%ee).