Biocatalytic approaches to hetero-Diels-Alder adducts of carbonyl compounds.
Very little information is available on hetero-Diels-Alderases for the assembly of heterocyclic products despite the synthetic value of these [4+2] cycloadditions. Hetero-Diels-Alderase antibodies raised against a bicyclic transition state analogue have been generated for the cycloaddition of ethylglyoxylate with an all-carbon diene. More recently, a conceptually novel biocatalytic approach to hetero-Diels-Alder (HDA) adducts derived from carbonyl dienophiles has been developed mirroring a stepwise aldol Michael mechanism instead of a concerted pathway. In this approach, the two key steps are an antibody-mediated kinetic resolution of beta-hydroxyenones and a subsequent ring-closure process. An attractive feature of this methodology is the possibility to convert the enantioenriched aldol intermediates into tetrahydropyranones or dihydropyranones. This bioorganic route is best applied for the preparation of enantioenriched HDA adducts derived from poorly electrophilic acceptors, therefore complementing existing catalytic routes to these adducts based on the use of small organocatalysts or chiral Lewis acids.
Gouverneur
Véronique
V
University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, OX1 3TA Oxford, UK. veronique.gouverneur@chem.ox.ac.uk
Reiter
Maud
M
D002384:Catalysis; D007659:Ketones / Q000737:chemistry*
D007659:Ketones