Development of a cysteine-catalyzed enantioselective Rauhut-Currier reaction.
Herein, we report a full account of the development of an enantioselective Rauhut-Currier process that affords products in high yields and enantioselectivities using a cysteine-based catalyst. While traditional Morita-Baylis-Hillman catalysts were found to be essentially ineffective, various derivatives of protected cysteine were found to exhibit extraordinary reactivity and enantiotopic control. Extensive screening of reaction conditions led us to discover the enhanced effects of water as an additive and the chelating power of potassium in achieving higher enantiomer ratios. Mechanistic experiments also provided insight on the potential mechanism of the reaction in addition to possible transition states that provide the absolute stereochemistry formed in the observed products. Also included is a brief survey of the reaction scope involving different ring sizes as well as functionalized substrates.
Aroyan
Carrie E
CE
Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
Dermenci
Alpay
A
Miller
Scott J
SJ
D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D003545:Cysteine / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000438:Alcohols; D007659:Ketones; D003545:Cysteine