A Carbene Catalysis Strategy for the Synthesis of Protoilludane Natural Products

Abstract

TheA rmillariaa nd Lactariusg enerao ff ungi producet he antimicrobiala nd cytotoxicm ellolide,p rotoilludane,a nd marasmanes esquiterpenoids. We report au nified synthetics trategyt oa ccesst he protoilludane, mellolide, and marasmanef amilieso fn atural products.T he keyf eatureso f theses yntheses are1 )the organocatalytic, enantioselective construction of keyc hirali ntermediates from as implea chiral precursor,2 )the utilityo fakey1 ,2-cyclobutanediol intermediatetoserve as aprecursor to each naturalproduct class, and3)a direct chemical conversion of ap rotoilludane to am arasmane throughs erendipitous ring contraction, whichp rovidese xperimentalsupport fortheir proposed biosynthetic relationships. Scheme 1. Overall synthesis plan. Supportinginformation (including experimental details) and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201705308. Angewandte Chemie Communications 9864 2017 Wiley-VCH Verlag GmbH &C o. KGaA, Weinheim Angew.C hem.I nt. Ed. 2017, 56,9 864 -9867 Scheme 2. Exploration of the NHC-catalyzed annulation strategy.D MS = dimethylsulfide, DIBAL-H = diisobutylaluminium hydride, DMP = Dess-Martin periodinane, PPA = polyphosphoric acid, DBU = 1,8-diazabicyclo(5.4.0)undec-7ene, LiHDMS = lithium bis(trimethylsilyl)amide, Tf = triflate. Angewandte Chemie Communications 9865

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

“…[39] In 2017, Yang and co-workers developed the total synthesis of (-)-pavidolide B (116, Scheme 13), involving an enantioselective organocatalytic cyclopropanation reaction as the key step. [40] They demonstrated that the asymmetric Michael addition/intramolecular-alkylation reaction of dimethyl 2bromo-malonate (108) and hexadienal 109 catalyzed by the amine catalyst (R)-13 led to the cyclopropane derivative 110. Further elaboration of 110 afforded (À )-pavidolide B (116) via a multistep sequence that included the Mitsunobu reaction, an annulation reaction, and the isomerization of the γ,δ-unsaturated enone 115 to the more stable α,β-unsaturated enone 116 (Scheme 13).…”

“…In 2017, Scheidt and co‐workers developed a unified strategy for the enantioselective total synthesis of protoilludane, mellolide, and marasmane families of natural products, in which the NHC‐catalysis played a key role [108] . As shown in Scheme 61, the annulation reaction of acyclic enone‐enal 571 under the catalysis of the N ‐heterocyclic carbene salt 572 led to the formation the vinyl lactone product 573 in a high yield and high stereoselectivities.…”

“…Among these natural products, echinocidins B ( 580 ) and D ( 577 ) belong to the protoilludane family; armillaridin ( 583 ) belongs to the mellolide family; and isovelleral ( 578 ) belongs to the marasmane family (Scheme 61). [108] …”

“…[107] In 2017, Scheidt and co-workers developed a unified strategy for the enantioselective total synthesis of protoilludane, mellolide, and marasmane families of natural products, in which the NHC-catalysis played a key role. [108] As shown in Scheme 61, the annulation reaction of acyclic enone-enal 571 under the catalysis of the N-heterocyclic carbene salt 572 led to the formation the vinyl lactone product 573 in a high yield and high stereoselectivities. Further elaborations afforded the tricyclic cis-diol 575 and the ring-contracted tricyclic aldehyde 576, which served as the key intermediates for the total synthesis.Desilylation of 575 yielded echinocidin D (577), whereas a desilylation of 576 followed by an oxidation led to isovelleral (578).…”

“…Among these natural products, echinocidins B (580) and D (577) belong to the protoilludane family; armillaridin (583) belongs to the mellolide family; and isovelleral (578) belongs to the marasmane family (Scheme 61). [108] In 2015, Erhardt and co-workers reported the total synthesis of (�)-glyceollin II (593) and (�)-dihydroglyceollin II (588) (Scheme 62). [109] They achieved the synthesis of the key intermediate 586 as a racemate through an NHC-catalyzed intramolecular benzoin condensation reaction of the ketoaldehyde 584, using the N-heterocyclic carbene salt 585 as the catalyst.…”