Enantioselective Michael Addition Reactions Catalyzed By Chiral Primary Amine Thioureas

As an important organocatalyst in asymmetric catalysis, chiral thioureas are rapidly emerging as high catalytic active, excellent enantioselective and ease of prepared and modified organocatalyst. Chiral thioureas have been succeeded in varieties of important asymmetric reactions, such as Michael, Mannich, Henry and Baylis-Hillman reactions.Most of the primary amine thioureas reported have an additional chiral unit except for the chiral diamine backbone. Herein we have applied chiral (1R,2R)-diphenylethane-1, 2-diamine derived primary amine thioureas without additional chiral moiety in the enantioselective Michael addition of isobutyraldehyde to nitroolefins. Under the optimized reaction conditions, in the presence of 15 mol% Cat 4, the Michael products were achieved in good yields (up to 98%) and excellent enantioselectivities (98->99% ee). Furthermore, when acetone/aromatic methyl ketone was used as Michael donor, the Michael reaction was achieved in good yields (up to 95%) with excellent enantiomeric excesses (91-98% ee) using 10 mol% Cat 4 as catalyst.Till now, there is no report on the primary amine thiourea catalyzed enantioselective Michael addition of nitroolefins with anthrone. We firstly have utilized primary amine thioureas to catalyze the asymmetric Michael addition of anthrone to nitroolefins. Under the optimized reaction conditions, the Michael adducts were achieved in excellent yields (up to 98%) and good enantioselectives (up to 86%ee) in the presence of 5 mol% Cat 1.To the best of our knowledge, nitrodienes were seldom used as acceptor in the enantioselective Michael reaction. And there was no systemic study on the enantioselective Michael addition of ketone with nitrodiene. We have firstly employed primary amine thioureas to catalyze the asymmetric Michael addition of ketones (aliphatic ketone/aromatic methyl ketone) to nitrodiene. Under the optimized reaction conditions, the desired products were obtained in good yields (up to 97%) and excellent enantioselective (up to 99% ee) in the presence of 10-30 mol% Cat 4.In addition, a series of N-heteroaryl substrates which have acetyl group were synthesized via PdCl2/(o-tolyl)3P catalyzed Heck reaction and hydrolysis. We studied the asymmetric Michael addition using N-heteroaryl methyl ketones as nucleophiles. Unfortunately, we didn't get the products.