Synthetic and computational studies on the tricarboxylate core of 6,7-dideoxysqualestatin H5 involving a carbonyl ylide cycloaddition-rearrangement.
Reaction of diazodiketoesters 17 and 28 with methyl glyoxylate in the presence of catalytic rhodium(II) acetate generates predominantly the 6,8-dioxabicyclo[3.2.1]octanes 29 and 30, respectively. Acid-catalysed rearrangement of the corresponding alcohol 31 favours, at equilibrium, the 2,8-dioxabicyclo[3.2.1]octane skeleton 33 of the squalestatins-zaragozic acids. Force field calculations on the position of the equilibrium gave misleading results. DFT calculations were correct in suggesting that the energy difference between 31 and 33 should be small, but did not always suggest the right major product. Calculation of the NMR spectra of the similar structures could be used to assign the isomers with a high level of confidence.
Hodgson
David M
DM
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, UK OX1 3TA. david.hodgson@chem.ox.ac.uk
Villalonga-Barber
Carolina
C
Goodman
Jonathan M
JM
Pellegrinet
Silvina C
SC
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D003198:Computer Simulation; D003500:Cyclization; D015394:Molecular Structure; D014233:Tricarboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry*
C465981:6,7-dideoxysqualestatin H5; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014233:Tricarboxylic Acids