Palladium Tandem Catalysis in the Atropodiastereoselective Synthesis of Indenes Bearing Central and Axial Chirality

Abstract

International audienceThe conversion of propargylic carbonates into allenes via Pd-catalyzed coupling with arylboronic acids, followed by tandem intramolecular Alder-ene cyclization, proceeds with remote diastereocontrol in the formation of indenes possessing two stereogenic elements (stereocenter and chiral axis). Highly configurationally stable atropisomers have been obtained with dr values up to >98:2. The reaction tolerates a range of commercially available functionalized arylboronic acids and allows the creation of C(sp2)–C(sp2) and C(sp2)–C(sp3) bonds in a single operation. Control experiments suggest that synergetic thermal and Pd-catalyzed cyclizations are likely to be involved in the second elementary step

A Rare Alder‐ene Cycloisomerization of 1,6‐Allenynes

“…This proposed process would allow for a mechanistic pathway that is distinct from most existing Alder-ene examples [10][11] in which the allene acts as the "ene" component with transfer of an allenylic H (R 1 HC=C=CHCHHR 2 ) to the enophile (as seen in Scheme 1b), rather than an allene H as proposed in Scheme 1c -or the allene acts as the enophile. [12] Allenes react with electron deficient perfluoroketones, however, with transfer of an allene H to the carbonyl oxygen similar to that proposed here in Scheme 1c. [14] A recent study demonstrated intramolecular Alder-ene reactions of allene-tethered arynes involving participation of the allene H or the allenylic H depending on the substitution pattern of the allene moiety.…”

Chiral Fidelity in the Diastereoselective and Enantiospecific Synthesis of Indenes from Axially Chiral Benzylidene Cyclanes

“…Cascade reactions have already been applied to the enantioselective construction of indenes . The originality of our approach is to combine the homologation of terminal alkynes with the trapping of the resulting allene in an Alder‐ene cyclization . Because of the distance between the alkynoate and cyclohexyl group, the isomerization of alkynoate 2 to allenoate 3 should lead to a pair of diastereomers in nearly equimolar amount.…”

“…[10] The originality of our approachi st oc ombinet he homologation of terminala lkynes [11] with the trapping of the resulting allene in an Alder-ene cyclization. [12] Because of the distance between the alkynoate and cyclohexyl group, the isomerization of alkynoate 2 to allenoate 3 should lead to ap air of diastereomers in nearly equimolar amount.I na ll likelihood, provided that the ring conformation is locked by ab ulky Rg roup,t he axially chiral alkylidene cyclohexane should control the axis-to-center chirality transfer in the cyclizations tep. The selection between the two diastereotopic axial hydrogenso nt he cyclohexyl moiety in the transition state should simultaneously control the second created stereocenter,w hatever the relative configurationo ft he allene axis.…”

Recent Advances in the Synthesis of Indenes

“…One year before Nechab reported another example of Pd‐catalyzed tandem process for the synthesis of indenes. Propargylic carbonates 80 were converted into allenes 81 via Pd‐catalyzed coupling with arylboronic acids.…”