Practical\nSynthesis of Macrobicyclic Thiolincosamines

Scalable\nsyntheses of the northern macrobicyclic thiolincosamine\nfragments of two structurally complex antibiotic candidates, BT-33\nand cresomycin, are presented. A key transformation in each route\nis the highly diastereoselective addition of a putative allenylzinc\nnucleophile to a common Ellman sulfinimine intermediate using a zinc-promoted\nBarbier-type propargylation protocol that is detailed herein. These\ntransformations proceed with dynamic kinetic resolution and use just\n1.2 equiv of each respective propargyl bromide precursor.