FeCl₃ Catalyzed Prins-Type Cyclization for the Synthesis of Highly Substituted Indenes: Application to the Total Synthesis of (±)-Jungianol and <i>epi</i>-Jungianol

A novel approach was developed for the synthesis of highly substituted indene derivatives, using an FeCl₃ catalyzed Prins-type cyclization reaction which was further applied in the total synthesis of jungianol and <i>epi</i>-jungianol

Biomimetic Enantioselective Total Synthesis of (−)-Petromindole

The first enantioselective total synthesis of (−)-petromindole, an architecturally distinct congener of indole diterpene family, has been achieved. Key features of this synthetic route include the scalable and concise synthesis of tricyclic allylic alcohol from enantiopure Wieland–Mischer ketone derivative, and TMSOTf-mediated, highly efficient biomimetic C-4 cyclization of indole derivative for the rapid construction of a hexacyclic skeleton of petromindole

Total Synthesis of Adunctin B

Total synthesis of (±)-adunctin B, a natural product isolated from <i>Piper aduncum</i> (Piperaceae), has been achieved using two different strategies, in seven and three steps. The efficient approach features highly atom economical and diastereoselective Friedel–Crafts acylation, alkylation reaction and palladium catalyzed Wacker type oxidative cyclization

Enantioselective Total Syntheses of (+)-Hostmanin A, (−)-Linderol A, (+)-Methyllinderatin and Structural Reassignment of Adunctin E

A one-step protocol has been developed for the enantioselective synthesis of hexahydrodibenzofuran derivatives using a modified Friedel–Crafts reaction. The developed method was applied to the synthesis of a series of natural products including (+)-hostmanin A, (+)-methyllinderatin, and (−)-linderol A. The synthetic and spectroscopic data investigations led to the structural reassignment of natural product adunctin E, which was further confirmed by single-crystal X-ray analysis

Biomimetic Total Syntheses of Borreverine and Flinderole Alkaloids

Dimeric indole alkaloids represent a structurally unique class of natural products having interesting biological activities. Recently, we reported the first total synthesis of flinderoles B and C, structurally unique and potent antimalarial natural products. Central to the design of the approach and by virtue of a one-pot, acid-catalyzed dimerization reaction, the route also provided total synthesis of the borreverine class of natural products. This full account details the progress of efforts that culminated in the protecting-group-free, six-step total synthesis of all of the flindersia alkaloids: dimethylisoborreverine, isoborreverine, flinderoles A–C, and their analogues. A biomimetic approach featuring a scalable and catalytic formal [3 + 2] cycloaddition and Diels–Alder reaction is outlined in detail. On the basis of the experimental observations, a detailed mechanism has been proposed for the dimerization of tertiary alcohol <b>28</b>

Biomimetic Enantioselective Total Synthesis of (−)-Mycoleptodiscin A

Biomimetic total synthesis of (−)-mycoleptodiscin A (<b>1</b>) was achieved starting from the enantiopure key intermediate, which was prepared by Friedel–Crafts reaction between 7-methoxyindole and chiral primary allylic alcohol. The crucial step in this synthesis was an intramolecular Friedel–Crafts reaction at C-4 of the indole derivative driven by the EDG/EWG within a compound that was rationally designed to prevent the cyclization reaction at the C-2 positon of indole, thereby successfully providing the complete carbon framework of <b>1</b>. This intramolecular Friedel–Crafts reaction at C-4 of indole derivative could be applied for the synthesis of other C-4-substituted indole alkaloid natural products

FeCl₃‑Catalyzed Intramolecular Michael Reaction of Styrenes for the Synthesis of Highly Substituted Indenes

An intramolecular FeCl₃-catalyzed Michael addition reaction of styrene, a poor nucleophile, onto α,β-unsaturated ketones was developed for the synthesis of highly substituted indene derivatives. The method was further applied to the total synthesis of the sesquiterpene natural products (±)-jungianol and 1-<i>epi</i>-jungianol

Asymmetric Total Synthesis of (+)-Verrubenzospirolactone and (+)-Capillobenzopyranol

The first asymmetric total synthesis of (+)-verrubenzospirolactone (1), a distinctive highly fused benzosesquiterpenoid, characterized by a pentacyclic skeletal structure, is realized through a concise 10-step synthetic pathway with an impressive 22.8% overall yield. Notable highlights of this synthetic endeavor include (i) the introduction of a Ru-catalyzed ortho C–H activation step, (ii) the application of Pd-catalyzed asymmetric allylic alkylation to establish a pivotal stereocenter at C-3 with an excellent enantiomeric excess, (iii) B-alkyl Suzuki–Miyaura coupling to construct a Diels–Alder precursor, and, ultimately, (iv) the successful deployment of an intramolecular Diels–Alder reaction to complete the synthesis of (+)-verrubenzospirolactone without erosion of the enantiomeric excess

Remarkable Switch of Regioselectivity in Diels–Alder Reaction: Divergent Total Synthesis of Borreverine, Caulindoles, and Flinderoles

Switchable reaction patterns of dimerization of indole substituted butadienes via a Lewis acid and thermal activation are reported. While under acidic conditions dimerization occurred around the internal double bond of the dienophile, a complete switch of regioselectivity was observed under thermal conditions, where dimerization occurred around the terminal double bond of the dienophile. This switch of regioselectivity was further exploited for the divergent total synthesis of structurally diverse indole alkaloid natural products

Remarkable Switch of Regioselectivity in Diels–Alder Reaction: Divergent Total Synthesis of Borreverine, Caulindoles, and Flinderoles

Switchable reaction patterns of dimerization of indole substituted butadienes via a Lewis acid and thermal activation are reported. While under acidic conditions dimerization occurred around the internal double bond of the dienophile, a complete switch of regioselectivity was observed under thermal conditions, where dimerization occurred around the terminal double bond of the dienophile. This switch of regioselectivity was further exploited for the divergent total synthesis of structurally diverse indole alkaloid natural products