Enantioselective Total Synthesis of (−)-Maoecrystal V

Abstract

The enantioselective synthesis of maoecrystal V, a cytotoxic polycyclic diterpene, is described. Key reactions in the synthesis include an intramolecular Heck reaction, an oxidative cycloetherification, and an intermolecular Diels-Alder reaction to forge the carbocyclic core in a concise and stereoselective manner. Late-stage amine and C-H oxidation is used to install the final functional groups required to complete the synthesis.

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

“…[103] In their approach, maoecrystal V was disconnected to dioxatetracyclic intermediate 171 , with the aim of fashioning the bicyclo[2.2.2]octan-2-one fragment using a bimolecular Diels–Alder (Scheme 17). Disconnection of tetracyclic intermediate 171 led Thomson and co-workers to select 4,4-dimethylcyclohexenone 172 and bromophenol 173 as the precursors to rings A and E. The synthesis began with the Baylis–Hillman reaction of cyclohexenone 172 with formaldehyde, followed by Sharpless asymmetric epoxidation of the resulting allylic alcohol to give 174 in moderate yield and high enantiopurity.…”

Total Synthesis of Maoecrystal P: Application of a Strained Bicyclic Synthon

“…During the evaluation of different protecting groups, we obtained a derivative of 15 and confirmed its structure by X‐ray diffraction (see Figure S1 in Supporting Information for details) . Eventually, we adopted a procedure involving the diacetylation of compound 15 followed by a one‐pot allylic oxidation to furnish enone 17 in 74 % overall yield; the major side product 16 could also be oxidized to 17 . Palladium‐catalyzed hydrogenolysis of the cyclopropane ring selectively cleaved the C14−C16 bond and afforded enone 18 in high yield .…”

Masked Ketenes as Dienophiles in the Diels–Alder Reaction

“…[69] Treatment of a,b-unsaturated ketone 50 with dithium diisopropylamide (LDA) and trimethylsilyl chloride (TMSCl) provided activated diene 51, which underwent a DA reaction with nitroethylene (45), followed by silyl enol ether hydrolysis, to give ketone 52 in 55 % yield. A two-step procedure was used to unmask the ketone, beginning with dithiane protection, followed by in situ reduction of the nitro group to yield amine 53.…”