Michael reaction of malonates to nitroolefins with chiral bifunctional organocatalysts, bearing both a thiourea and tertiary amino group, afforded Michael adducts with high yields and enantioselectivities (up to 95%, up to 93% ee).

Hydrogen-bonding interaction plays a crucial role in the molecular recognition and activation processes of various biologically important reactions that are mediated by enzymes and antibodies in living organisms. Recently, it has been shown that a hydrogen-bonding donor can be used as a general acid catalyst for various types of reactions in organic chemistry. In this article, we describe enantioselective reactions catalyzed by urea and thiourea derivatives as general acid catalysts as well as diastereoselective reactions. This perspective provides an overview of this rapidly growing field.

[reaction: see text] The aza-Henry reaction of imines with nitroalkanes was promoted by chiral thiourea with an N,N-dimethylamino group to give beta-nitroamines with good enantioselectivity. Various N-protected imines were examined as substrates. N-Phosphinoylimine gave the best result in terms of chemical yield and enantioselectivity (up to 91% yield, up to 76% ee).

Experimental procedure for preparation of catalyst 1b and its characterization data: S2.Characterization data of catalysts 1c-i: S4.The results of Petasis-type reaction of 2a, 2b and 3 with 4A using catalysts 1a-i: S6.General procedure for Petasis-type reaction of 2a-f: S7.Characterization data of obtained compounds 5a-6aF: S7.Conversion of the adduct 6aC to (+)-galipinine 7 and characterization data: S10.

We have developed several multifunctional thiourea catalysts bearing a tertiary amine or an 1,2-amino alcohol in expectation of their synchronous activation of a nucleophile and an electrophile through both acid-base and hydrogen-bonding interactions. From these studies, it was revealed that the weak acidity of thioureas compared with metallic Lewis acids could be overcome by this modification. The bifunctional aminothiourea could be used efficiently for a wide range of diastereoselective and enantioselective nucleophilic reactions such as Michael addition of 1,3-dicarbonyl compounds to nitroolefines, aza-Henry reaction of nitroalkanes to N-Boc imines, and hydrazination of cyclic b b-keto esters. We also discovered that multifunctional thiourea catalyst, bearing an 1,2-amino alcohol moiety, significantly accelerated the Petasis-type reaction of alkenylboronic acids to Nphenoxycarbonyl quinolinium salts, prepared from quinolines and phenyl chloroformate, to afford 1,2-addition products with high enantioselectivity (up to 97% ee). Furthermore, to expand the synthetic applicability of the thiourea-catalyzed asymmetric reactions, tandem organocatalyzed reactions were explored to establish the concise one-pot synthesis of chiral densely functionalized three-, five-, and six-membered compounds.