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Free keywords:
antibiotics; asymmetric hydroformylation; macrolides; redox-isomerization; ruthenium; trans-hydrostannation
Abstract:
Proof‐of‐concept is provided that a large estate of 16‐membered macrolide antibiotics can be reached by a “unified” approach. The key building block was formed on scale by an asymmetric vinylogous Mukaiyama aldol reaction; its alkene terminus was then converted either into the corresponding methyl ketone by Wacker oxidation or into a chain‐extended aldehyde by catalyst‐controlled branch‐selective asymmetric hydroformylation. These transformations ultimately opened access to two structurally distinct series of macrolide targets. Notable late‐stage maneuvers comprise a rare example of a ruthenium‐catalyzed redox isomerization of an 1,3‐enyne‐5‐ol into a 1,3‐diene‐5‐one derivative, as well as the elaboration of a tertiary propargylic alcohol into an acyloin by trans‐hydrostannation/Chan‐Lam‐type coupling. Moreover, this case study illustrates the underutilized possibility of forging complex macrolactone rings by transesterification under essentially neutral conditions.
