Conjugate Addition to Acylketene Acetals Derived from 1,8-Dihydroxynaphthalene and Its Application To Synthesize the Proposed Structure of Spiropreussione A

A conjugate addition of diverse nucleophiles to acylketene acetals derived from 1,8-dihydroxynaphthalene (DHN) is developed for the formation of its 3-oxoalkan-1-one acetals. The initial acylketene acetals are prepared via double oxa-Michael addition of DHN to 1-bromo-1-propyn-3-ones. Carbonucleophiles, including organocopper reagents and active methylene compounds, and heteroatom nucleophiles were introduced under basic conditions. This method is applied for synthesizing spiropreussione A; the proposed structure does not correspond to that of the authentic natural product

Total Syntheses of (+)- and (−)-Tetrapetalones A and C

Described herein are syntheses of the naturally occurring polyketides (−)-tetrapetalones A and C and their respective enantiomers. The employed strategy involves initial assembly of a masked <i>N-</i>aryl tetramic acid which is advanced via a highly selective conjugate addition/intramolecular Friedel–Crafts acylation sequence to deliver a key azepine intermediate. Application of recently developed C–H activation chemistry and subsequent Heck cyclization delivers the aglycone framework in an overall 12 steps. Resolution of the aglycone via stereospecific glycosylation with an enantiopure glycosyl donor followed by separation of the derived diastereomers enables further advancement to either (+)- or (−)-tetrapetalones A and C