Enantioselective Synthesis of Functionalized Diazaspirocycles from 4‐Benzylideneisoxazol‐5(4H)‐one Derivatives and Isocyanoacetate Esters
Enantioenriched spirocyclic compounds bearing three contiguous stereocenters and high functionalization were obtained through a formal [3+2] cycloaddition reaction catalyzed by a cooperative system. The spiro compounds were synthesized from 4-arylideneisoxazol-5-ones and isocyanoacetate esters using a bifunctional squaramide/Brønsted base organocatalyst derived from a Cinchona alkaloid and silver oxide as Lewis acid. This method afforded two out of the four possible diastereomers with good yields and high enantiomeric excess for both diastereomers.
Enantioselective Synthesis of 5-Trifluoromethyl-2-oxazolines under Dual Silver/Organocatalysis.
[EN] The first enantioselective formal [3 + 2] cycloaddition between ¿-isocyanoesters and trifluoromethylketones to give 5-trifluoromethyl-2-oxazolines bearing two contiguous stereogenic centers, one of them being a quaternary stereocenter substituted with a CF3 group, has been developed. The reaction is based upon a multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as Lewis acid. The reaction could be achieved with a range of aryl and heteroaryl trifluoromethyl ketones, and the resulting oxazolines were obtained with good to excellent diastereo- and enantioselectivity.
Enantioselective synthesis of chiral oxazolines from unactivated ketones and isocyanoacetate esters by synergistic silver/organocatalysis
[EN] A multicatalytic approach that combines a bifunctional Brønsted base¿squaramide organocatalyst and Ag+ as Lewis acid has been applied in the reaction of unactivated ketones with tert-butyl isocyanoacetate to give chiral oxazolines bearing a quaternary stereocenter. The formal [3+2] cycloaddition provided high yields of the corresponding cis-oxazolines with good diastereoselectivity and excellent enantioselectivity, being applied to aryl¿alkyl and alkyl¿alkyl ketones.
Catalytic Diastereo- and Enantioselective Synthesis of 2-Imidazolinones.
Chiral cyclic ureas (2-imidazolinones) were prepared by the reaction of nitrones and isocyanoacetate esters using a multicatalytic system that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as a Lewis acid. The reaction could be achieved with a range of nitrones derived from aryl- and cycloalkylaldehydes with moderate diastereo- and good enantioselectivity. A plausible mechanism involving an initial formal [3 + 3] cycloaddition of the nitrone and isocyanoacetate ester, followed by rearrangement to an aminoisocyanate and cyclization to the imidazolinone, is proposed.
CCDC 1818227: Experimental Crystal Structure Determination
Related Article: Pablo Martínez-Pardo, Gonzalo Blay, M. Carmen Muñoz, José R. Pedro, Amparo Sanz-Marco, Carlos Vila|2018|Chem.Commun.|54|2862|doi:10.1039/C8CC00856F
CCDC 1844052: Experimental Crystal Structure Determination
Related Article: Pablo Martínez-Pardo, Gonzalo Blay, Carlos Vila, Amparo Sanz-Marco, M. Carmen Muñoz, and José R. Pedro|2019|J.Org.Chem.|84|314|doi:10.1021/acs.joc.8b02808
CCDC 1844051: Experimental Crystal Structure Determination
Related Article: Pablo Martínez-Pardo, Gonzalo Blay, Carlos Vila, Amparo Sanz-Marco, M. Carmen Muñoz, and José R. Pedro|2019|J.Org.Chem.|84|314|doi:10.1021/acs.joc.8b02808