Practical Synthetic Procedures for the Iron-Catalyzed Intermolecular Olefin Aminohydroxylation Using Functionalized Hydroxylamines.

A set of practical synthetic procedures for the iron-catalyzed intermolecular olefin aminohydroxylation reactions in gram scale is reported. In these transformations, a bench-stable functionalized hydroxylamine is applied as the amination reagent. This method is compatible with a broad range of synthetically valuable olefins including those that are incompatible with the existing aminohydroxylation methods. It also provides valuable amino alcohol building blocks with regio- and stereo-chemical arrays that are complementary to known methods.

Iron(II)-catalyzed intermolecular amino-oxygenation of olefins through the N-O bond cleavage of functionalized hydroxylamines.

An iron-catalyzed diastereoselective intermolecular olefin amino-oxygenation reaction is reported, which proceeds via an iron-nitrenoid generated by the N-O bond cleavage of a functionalized hydroxylamine. In this reaction, a bench-stable hydroxylamine derivative is used as the amination reagent and oxidant. This method tolerates a range of synthetically valuable substrates that have been all incompatible with existing amino-oxygenation methods. It can also provide amino alcohol derivatives with regio- and stereochemical arrays complementary to known amino-oxygenation methods.

Organocatalyzed Michael-Michael cascade reaction: asymmetric synthesis of polysubstituted chromans.

An enantioselective cascade Michael-Michael reaction between chalcones enolates and nitromethane catalyzed by a bifunctional thiourea is developed. This reaction provides a mild but efficient approach to chiral benzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities, and the benzopyrans can be easily transformed to the corresponding tricyclic product.

Organocatalytic aza-Michael-Michael cascade reactions: a flexible approach to 2,3,4-trisubstituted tetrahydroquinolines.

Cascading like dominos: An efficient and highly enantioselective synthesis of 2,3,4-trisubstituted tetrahydroquinolines through cascade aza-Michael-Michael reactions was developed. Tetrahydroquinolines were obtained in excellent yields, high enantioselectivities, and good diastereoselectivities, and could be easily transformed into ring-fused tetrahydroquinolines (see scheme).

Highly enantioselective synthesis of polysubstituted tetrahydroquinolines via organocatalytic Michael/Aza-Henry tandem reactions.

Highly enantioselective chiral bifunctional thiourea catalyzed asymmetric tandem reactions for synthesis of substituted tetrahydroquinolines are described. Substituted tetrahydroquinolines were given in good yields (up to 98%), high enantioselectivities (up to >99% ee), and diastereoselectivities (up to 20:1 dr).