Asymmetric Diels–Alder reaction of 3-(acyloxy) acryloyl oxazolidinones: optically active synthesis of a high-affinity ligand for potent HIV-1 protease inhibitors

RSC Advances

RSC Adv., 2019, 9, 41755–41763

We describe here our investigation of the asymmetric Diels–Alder reaction of chiral 3-(acyloxy)acryloyl

oxazolidinones as dienophiles in various Lewis-acid promoted reactions with cyclopentadiene. The

resulting highly functionalized cycloadducts are useful intermediates for the synthesis, particularly for the

optically active synthesis of 6-5-5 tricyclic hexahydro-4H-3,5-methanofuro[2,3-b]pyranol (3) with five

contiguous chiral centers. This stereochemically defined crown-like heterocyclic derivative is an

important high affinity ligand for a variety of highly potent HIV-1 protease inhibitors. Among the various

dienophiles and Lewis acid-mediated reactions surveyed, 3-(4-methoxybenzoyl)acryloyl oxazolidinone

as the dienophile and diethylaluminum chloride as the Lewis-acid provided the desired endo product

with excellent diastereoselectivity. The cycloaddition was carried out in multi-gram scale and the

cycloadduct was efficiently converted to alcohol 3 with high enantiomeric purity. The optically active

ligand was then transformed into potent HIV-1 protease inhibitor 2.

December 2019
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