Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes via a decarboxylative aldol cyclization

The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-ketoesters via an interrupted asymmetric allylic alkylation is disclosed. Substrates possessing pendant aldehydes undergo decarboxylative enolate formation in the presence of a chiral Pd catalyst and subsequently participate in an enantio- and diastereoselective, intramolecular aldol reaction to furnish spirocyclic β-hydroxy ketones which may be oxidized to the corresponding enantioenriched diketospiranes. Additionally, this chemistry has been extended to α-allylcarboxy lactam substrates leading to a formal synthesis of the natural product (−)-isonitramine

Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes via a decarboxylative aldol cyclization

The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-ketoesters via an interrupted asymmetric allylic alkylation is disclosed. Substrates possessing pendant aldehydes undergo decarboxylative enolate formation in the presence of a chiral Pd catalyst and subsequently participate in an enantio- and diastereoselective, intramolecular aldol reaction to furnish spirocyclic β-hydroxy ketones which may be oxidized to the corresponding enantioenriched diketospiranes. Additionally, this chemistry has been extended to α-allylcarboxy lactam substrates leading to a formal synthesis of the natural product (−)-isonitramine

NHC-Catalyzed Enantioselective Dearomatizing Hydroacylation of Benzofurans and Benzothiophenes for the Synthesis of Spirocycles

Benzofurans and benzothiophenes have been efficiently employed as substrates in an enantioselective intramolecular hydroacylation. Breaking aromaticity in a 5-<i>exo</i>-<i>trig</i> cyclization of easily accessible heteroarenes by NHC-catalyzed hydroacylation gives access to a simple class of mainly unexplored spirocycles with up to 99% enantiomeric excess (<i>ee</i>). The formed product class bears interesting three-dimensional pseudoaxial chirality and shows typical ketone reactivity. Density functional theory (DFT) calculations reveal erosion of the <i>ee</i> via a stepwise mechanism bearing a hetero Wheland intermediate. Theoretical data are in agreement with deuterium-labeling studies and a linear correlation between electronics (σ) and the <i>ee</i>