@article { ISI:000385054300003,
	title = {Catalytic Asymmetric Synthesis of Morpholines. Using Mechanistic Insights To Realize the Enantioselective Synthesis of Piperazines},
	journal = {JOURNAL OF ORGANIC CHEMISTRY},
	volume = {81},
	number = {19},
	year = {2016},
	month = {OCT 7},
	pages = {8696-8709},
	abstract = {An efficient and practical catalytic approach for the enantioselective synthesis of 3-substituted morpholines through a tandem sequential one-pot reaction employing both hydroamination and asymmetric transfer hydrogenation reactions is described. Starting from ether-containing aminoalkyne substrates, a commercially available bis(amidate)bis(amido)Ti catalyst is utilized to yield a cyclic imine that is subsequently reduced using the Noyori-Ikariya catalyst, RuCl {[}(S,S)-Ts-DPEN] (eta(6)-p-cymene), to afford chiral 3-substituted morpholines in good yield and enantiomeric excesses of >95\%. A wide range of functional groups is tolerated. Substrate scope investigations suggest that hydrogen-bonding interactions between the oxygen in the backbone of the ether-containing substrate and the {[}(S,S)-Ts-DPEN] ligand of the Ru catalyst are crucial for obtaining high ee{\textquoteright}s. This insight led to a mechanistic proposal that predicts the observed absolute stereochemistry. Most importantly, this mechanistic insight allowed for the extension of this strategy to include N as an alternative hydrogen bond acceptor that could be incorporated into the substrate. Thus, the catalytic, enantioselective synthesis of 3-substituted piperazines is also demonstrated.},
	issn = {0022-3263},
	doi = {10.1021/acs.joc.6b01884},
	author = {Lau, Ying Yin and Zhai, Huimin and Schafer, Laurel L.}
}
