Stereodivergent synthesis of functionalized tetrahydropyrans accelerated by mechanism-based allylboration and bioinspired oxa-michael cyclization

Article abstract of DOI:10.1002/anie.201600558

A stereodivergent strategy enabled by bioinspired oxa-Michael cyclization was developed for the synthesis of functionalized tetrahydropyrans on the basis of the inherent symmetry in 1,3-diols, the symmetries of which were tunable by stereoselective hydroboration of an allene with a variety of alkylborane reagents and subsequent allylation of an aldehyde. The mechanism-based utilization of monoalkyl borane in the hydroboration and allylation cascade is unprecedented. Symmetry breakdown: The thermodynamic and kinetic hydroboration of allenes and subsequent allylboration provide a key stereodefinable module with a latent symmetry. Following a deprotection/chain elongation/oxa-Michael cyclization sequence, the stereocogeners of highly functionalized tetrahydropyrans were synthesized for rapid access to structural motifs found in bioactive polyketides.