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 N-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.

Described herein are synthetic efforts toward the synthesis of hippolachnin A. Two independently devised routes from the Brown and Wood groups allowed for the synthesis of hippolachnin A from the unusual starting material, quadricyclane, by harnessing the power of late-stage C–H oxidation. Collaborative union of the best features of the two routes allowed for preparation of the molecule with improved efficiency.

Efforts to install the core azepine ring in tetrapetalone A via a palladium π-allyl cascade reaction failed due to competing pathways that included an unexpected and interesting TMM-like cycloaddition reaction that delivers a complex tricyclic ring system.

A method for chemoselective carbonyl ylide formation utilizing the Rh(II) catalyzed decomposition of electronically differentiated diazo malonates is disclosed. Treatment of ethyl, trifluoro ethyl diazo malonate with a Rh(II) catalyst selectively forms a carbonyl ylide from the relatively electron rich ethyl ester. This carbonyl ylide can be trapped by various alkynes giving highly functionalized oxabicyclic compounds in a chemo-, regio-, and diastereoselective fashion.