Enantioselective iodolactonization to prepare ε-lactone rings using hypervalent iodine.

Despite the rapid growth of enantioselective halolactonization reactions in recent years, most are effective only when forming smaller (6,5,4-membered) rings. Seven-membered ε-lactones, are rarely formed with high selectivity, and never without conformational bias. We describe the first highly enantioselective 7-exo-trig iodolactonizations of conformationally unbiased ε-unsaturated carboxylic acids, effected by an unusual combination of a bifunctional BAM catalyst, I2, and I(iii) reagent (PhI(OAc)2:PIDA).

Copper Catalyzed Regioselective and Stereospecific Aziridine Opening with Pyridyl Grignard Nucleophiles.

Copper catalyzed regioselective and stereospecific coupling between aziridines and in situ generated pyridine Grignard reagents is reported. This method provides ß-pyridylethylamines with diverse structures and functionalities from aziridines and iodopyridines. ß-Pyridylethylamines are potential scaffolds for the synthesis of biologically active compounds often found in pharmaceuticals. The synthesis of challenging chiral dihydroazaindoles was also achieved through mild one-pot reaction conditions via aziridine opening followed by nucleophilic cyclization.

Catalytic, Enantioselective Synthesis of Cyclic Carbamates from Dialkyl Amines by CO2-Capture: Discovery, Development, and Mechanism.

Cyclic carbamates are a common feature of small-molecule therapeutics, offering a constrained hydrogen bond acceptor that is both polar and sterically small. Methods for their preparation most often focus first on amino alcohol synthesis and then reaction with phosgene or its equivalent. This report describes an enantioselective synthesis of cyclic carbamates in which carbon dioxide engages an unsaturated basic amine, facilitated by a bifunctional organocatalyst designed to stabilize a carbamic acid intermediate while activating it toward subsequent enantioselective carbon-oxygen bond formation. Six-membered cyclic carbamates are prepared in good yield with high levels of enantioselection, as constrained 1,3-amino alcohols featuring a chiral tertiary alcohol carbon. Spectroscopic analysis (NMR, DOSY) of various substrate-reagent combinations provides insight into the dominant species under the reaction conditions. Two peculiar requirements were identified to achieve highest consistency: a "Goldilocks" amount of water and the use of a noncrystalline form of the ligand. These atypical features of the final protocol notwithstanding, a diverse range of products could be prepared. Their functionalizations illustrate the versatility of the carbamates as precursors to enantioenriched small molecules.