Asymmetric Organocatalytic Synthesis of aza-Spirocyclic Compounds from Isothiocyanates and Isocyanides

The spirocyclic motif is present in natural products, chiral ligands, and compounds of pharmacological interest. Isothiocyanates as well as isocyanides bearing electron-withdrawing groups in the α-position can be deprotonated and react as formal dipoles on account of the presence of a nucleophilic carbanion and an electrophilic atom in the isothiocyanate or isocyanide functional groups. In the last years a number of procedures involving the formal [3+2] cycloaddition reaction of isothiocyanates or isocyanides with cyclic compounds bearing electrophilic exocyclic double bonds have been developed for the enantioselective synthesis of aza-spirocyclic compounds. Among them, organocatalysis has played a predominant role in the development of asymmetric versions for these reactions. The synthesis of spirooxindoles by using this methodology has received especial attention, although other spirocyclic scaffolds are available depending on the structure of the dipolarophiles and the formal isothiocyanate and isocyanide dipoles

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

Metal-Free Diastereo- and Enantioselective Dearomative Formal [3 + 2] Cycloaddition of 2-Nitrobenzofurans and Isocyanoacetate Esters

The diastereo- and enantioselective dearomative formal [3 + 2] cycloaddition of 2-nitrobenzofurans and α-aryl-α-isocyanoacetate esters provides tricyclic compounds bearing the 3a,8b-dihydro-1H-benzofuro[2,3-c]pyrrole framework with three consecutive stereogenic centers. The reaction was enabled by a cupreine-ether organocatalyst. The reaction products were obtained with almost full diastereoselectivity and with excellent enantiomeric excesses for a number of substituted 2-nitrobenzofurans and isocyanoacetates

Enantioselective Synthesis of Functionalized Diazaspirocycles from 4‐Benzylideneisoxazol‐5(4 H

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