Pd‐Catalyzed Diastereoselective Intramolecular Amide α‐C−H Arylation in Sterically Hindered Monospirooxindole Motifs

Abstract

This paper reveals the diastereoselective Pd‐catalyzed intramolecular α‐C(sp3)−H arylation in amides. The intermolecular and intramolecular α‐arylation of tertiary C(sp3)−H bond of carbonyl compounds have been well documented in the literature. Nevertheless, the diastereoselective intramolecular α‐arylation of tertiary C(sp3)−H bond involving sterically hindered spirocyclic carbonyl substrates, especially amides remains a less explored task. Accordingly, we have demonstrated the diastereoselective Pd‐catalyzed intramolecular amide α‐arylation of tertiary C(sp3)−H bond using monospirooxindole‐based carboxamide substrates and construction of various sterically hindered 1,2‐bisspirooxindolopyrrolidines possessing contiguous vicinal quaternary stereocenters with high diastereoselectivity. Monospirooxindole‐based carboxamide substrates suitably positioned with an aryl halide unit and tertiary α‐C−H bond, which were required for investigating the intramolecular α‐C(sp3)−H arylation were assembled via the stereoselective [3+2] cycloaddition of azomethine ylides with acrylamides. The stereochemistry of monospirooxindoles and 1,2‐bisspirooxindolopyrrolidines possessing contiguous vicinal quaternary stereocenters was assigned based on the X‐ray structure analyses of representative compounds.magnified image

N-Heterocyclic carbene complexes enabling the α-arylation of carbonyl compounds

“…77 Scheme 49 Diastereoselective Pd-catalyzed intramolecular amide a-C-H arylation, as described by Babu and Shukla. 78 Scheme 50 Palladium catalyzed a-arylation of ketoimines, as described by Osuka et al…”

“…73 C(sp 3 )-H bond using mono spiro-oxindole-based carboxamide substrates and the synthesis of various sterically hindered 1,2-bisspirooxindolopyrrolidines possessing contiguous vicinal quaternary stereocenters with high diastereoselectivity. 78 Among the tested catalytic systems, the most effective was the PEPPSI complex 13 in the presence of NaOtBu (Scheme 49).…”

Decade Advance of Isatin in Three‐component Reactions

“…Azomethine ylide intermediates could be generated in situ from decarboxylative condensation of isatins and α ‐amino acids [19a–g] . α ‐Amino acids like N ‐alkyl glycines [19a,e] and sarcosine [19b–d,f] were frequently employed for the synthesis of spirooxindoles 19.1 via a similar mechanism. Condensation 19.2 , esterification 19.3 , decarboxylation 19.4 and 1,3‐dipolar cycloaddition 19.5 were involved during the process.…”

Diastereoselective palladium-catalyzed functionalization of prochiral C(sp3)–H bonds of aliphatic and alicyclic compounds

“…When the Pd( ii )-catalyzed, DG-aided functionalization of the C(sp 3 )–H bonds was emerging, the Pd(0)-catalyzed direct intramolecular arylation of the C(sp 3 )–H bonds was explored by various research groups in parallel. 4,81–84 There exist noteworthy examples of diastereoselective Pd(0)-catalyzed direct intramolecular arylation of prochiral C(sp 3 )–H bonds, affording cyclic compounds containing contiguous stereogenic centers. 4,81–84 Baudoin reported 81 a an efficient, Pd(0)-catalyzed, binepine ligand-enabled, asymmetric, intramolecular arylation of the prochiral C(sp 3 )–H bonds of substrate 68a .…”

“…4,81–84 There exist noteworthy examples of diastereoselective Pd(0)-catalyzed direct intramolecular arylation of prochiral C(sp 3 )–H bonds, affording cyclic compounds containing contiguous stereogenic centers. 4,81–84 Baudoin reported 81 a an efficient, Pd(0)-catalyzed, binepine ligand-enabled, asymmetric, intramolecular arylation of the prochiral C(sp 3 )–H bonds of substrate 68a . This process afforded fused cyclopentane motif 68b containing contiguous stereogenic centers (Scheme 34).…”