Highly Enantioselective, Organocatalytic, and Scalable Synthesis of a Rare cis,cis‐Tricyclic Diterpenoid

Abstract

A highly enantioselective, organocatalytic, and scalable synthesis of a very unusual cis‐decalin‐cis‐hydrindane tricyclic diterpenoid system has been achieved. Despite the prevalent pharmacological space that the related trans,trans and trans,cis‐systems occupy, there have been no reports of an asymmetric synthesis of the cis,cis systems in the literature until now. We demonstrate the flexibility of our approach not only through access to a diverse range of products, all of which are attained in exceptionally high selectivities, but also by showing their easy conversion to the corresponding trans,cis‐system and other derivatives.

Chasing Polycyclic Natural Products: 5/6/5‐ or 5/6/6‐Carbotricyclic Scaffold Construction via Stereodivergent Diels‐Alder Reaction of Chiral Hydrindanes and Their Boron Complexes

“…This all‐ trans ‐cyclohexane should be energetically favored [67,68] . A similar epimerization under acidic conditions has been reported for a related cis ‐ cis ‐substituted 5/6/6‐membered scaffold [69] . Furthermore, the ratio of the ( R,R )‐configured 10 isomers was nearly equimolar to ( X,S )‐configured 10 diastereomers at 140 °C and 190 °C.…”

“…[67,68] A similar epimerization under acidic conditions has been reported for a related cis-cis-substituted 5/6/6-membered scaffold. [69] Furthermore, the ratio of the (R,R)configured 10 isomers was nearly equimolar to (X,S)-configured 10 diastereomers at 140 °C and 190 °C. This means, with acyclic 2,3-dimethylbutadiene 9 we did not observe a diastereofacial selectivity as we did for cyclopenta-and cyclohexadiene 4a,b.…”

Model Synthetic Study of Tutin, a Picrotoxane-Type Sesquiterpene: Stereoselective Construction of a <i>cis</i>-Fused 5,6-Ring Skeleton

“…18,19) In fact, reactions for desymmetrization of the 1,3-cyclopentanedione moiety have been reported by various groups. [20][21][22][23][24][25][26][27] However, their application in the synthesis of picrotoxane-type sesquiterpenes has not been explored. In this reaction, there are two possible reaction pathways starting from enolate intermediate 8: an intramolecular attack of the enolate anion on carbon A to produce 9 or its attack on carbon B to produce 6 (Fig.…”

Catalysts’ evolution in the asymmetric conjugate addition of nitroalkanes to electron-poor alkenes

“…Ready access to the uncommon cis , cis -tricyclic diterpenoid skeleton can be achieved by reaction of functionalized nitroethylcycloalkanediones 27 with cyclohexenone in the presence of chiral diamine catalyst 22 (Scheme 21). 51 Adducts 28 are formed as an equimolar epimeric mixture with excellent control of the ring stereocenter. The subsequent intramolecular aldol reaction, catalyzed by boron trifluoride etherate, affords the target tricyclic derivatives with outstanding stereocontrol, considering that in the six-membered ring transition state, the most favorable approach entails a pseudoequatorial position of the nitro group and attack of the enolate Si side to the ketone.…”