A Domino Process toward Functionally Dense Quaternary Carbons through Pd-Catalyzed Decarboxylative C(sp³)–C(sp³) Bond Formation

Abstract

An efficient protocol was developed to construct functionally dense quaternary carbons with concomitant formation of a new Csp-Csp bond via Pd-catalyzed decarboxylative transformation of vinyl cyclic carbonates. This redox-neutral catalytic system features stereocontrolled formation of multisubstituted allylic scaffolds with an aldehyde functionality generated in situ, and it typically can be performed at room temperature without any additives. DFT calculations provide a rationale toward the selective formation of these compounds and reveal a complex mechanism that with the help of microkinetic models is able to reproduce the nontrivial dependence of the identity of the product on the nature of the substituents in the substrate.

Palladium‐Titanium Relay Catalysis Enables Switch from Alkoxide‐π‐Allyl to Dienolate Reactivity for Spiro‐Heterocycle Synthesis

“…[6] Notably,all these reported systems are based on the classical reactivity of electrophilic Pd-p-allyl (plus nucleophilic alkoxide). [7] Theaurone 1a [8] (Table 1) and the corresponding imines [9] have found much use in stereoselective cycloadditions in the past few years.V arious benzofuran-fused heterocycles were prepared in this way,a nd is ac ommon structural motif in al arge number of bioactive compounds. In particular,a n unprecedented umpolung of VECs is achieved: I is converted into anucleophilic dienolate species with palladium-titanium relay catalysis,w hich enables ah ighly diastereoselective [4+ +2] cycloaddition to access [6,5] spirocycles (pathway B).…”

“…It is noteworthy that during the preparation of our manuscript, the group of Kleij reported am echanistically related and elegant example of self-coupling of VECs through allylic alkylation of the enolate. [7] Theaurone 1a [8] (Table 1) and the corresponding imines [9] have found much use in stereoselective cycloadditions in the past few years.V arious benzofuran-fused heterocycles were prepared in this way,a nd is ac ommon structural motif in al arge number of bioactive compounds. [10] Based on our previous synthesis of nine-membered heterocycles, [5] we hypothesized that the switch of 1a might enable an attack of the alkoxide to the internal position of the Pd-p-allyl system in the final cyclization step for the synthesis of the seven-membered heterocycle 3.D espite much experimentation by modifying the palladium-catalyzed procedure,n o formation of 3 was observed.…”

Formal Synthesis of Indolizidine and Quinolizidine Alkaloids from Vinyl Cyclic Carbonates

“…Herein, we report on a highly flexible and general synthesis of indolizidine and quinolizidine alkaloids taking advantage of the modular and accessible nature of VCCs (Scheme ). Importantly, our strategy relies on the excellent stereoselectivity achieved in the conversion of VCCs under palladium catalysis, which sets up the formal alkaloid syntheses by providing precursors with the requisite functional groups and double‐bond configuration. Moreover, by slightly adjusting the synthetic route, we were able to access 2‐ and 3‐substituted indolizidine alkaloids through stereodefined homoallylic nitroalkane intermediates.…”

Diversity‐Orientated Stereoselective Synthesis through Pd‐Catalyzed Switchable Decarboxylative C−N/C−S Bond Formation in Allylic Surrogates

“…The structure of 9 reveals that the Pd center is η 3 ‐ligated by the allyl fragment and the hydromethyl group is orientated syn to the metal center. Such a π‐allyl Pd complex is rather distinct from the DFT‐computed six‐membered palladacycle recently determined in the functionalization of VECs with various nucleophiles ,,,. To examine whether this Pd‐complex 9 is catalytically competent, it was subjected to the optimized conditions reported in Table .…”