PyBidine–Cu(OTf)₂‐Catalyzed Asymmetric [3+2] Cycloaddition with Imino Esters: Harmony of Cu–Lewis Acid and Imidazolidine‐NH Hydrogen Bonding in Concerto Catalysis

Abstract

A bis(imidazolidine)pyridine (PyBidine)-Cu(OTf)2 complex catalyzing the endo-selective [3+2] cycloaddition of nitroalkenes with imino esters was applied to the reaction of methyleneindolinones with imino esters to afford spiro[pyrrolidin-3,3'-oxindole]s in up to 98 % ee. X-ray crystallographic analysis of the PyBidine-Cu(OTf)2 complex and DFT calculations suggested that an intermediate Cu enolate of the imino ester reacts with nitroalkenes or methyleneindolinones, which are activated by NH-hydrogen bonding with the PyBidine-Cu(OTf)2 catalyst.

Highly Stereoselective [3+2] Cycloadditions of Chiral Palladium‐Containing N1‐1,3‐Dipoles: A Divergent Approach to Enantioenriched Spirooxindoles

“…[2c, 4,5] The first example was reported by the Gong group in 2009, disclosing ac hiral Brønsted acid-catalysed [3+ +2] cycloadditiono fi ns itu generatedi mino esters with methyleneindolinones.…”

“…Many other robust catalysts ystems with chiral organic molecules [4] or chiral Lewis acids [5] have been also established by Wang, Arai and Yamanaka, as well as by many other groups.G iven the fundamental significance of diversity-oriented synthesis, [6] we herein discloseapalladium-catalysed asymmetric [3+ +2] cycloaddition reactiono fP d-containing N 1 -1,3-dipoles with methyleneindolinones. This cycloaddition provides ad ivergents ynthetic approach to functional group-enriched 3,3'-pyrrolidonyl spirooxindoles.…”

“…[2,3] Consequently,awide range of synthetic protocols have been developed to stereoselectively synthesise such molecules. [2,4,5] In particular, catalytic asymmetric [3+ +2] cycloaddition reactions of 1,3-dipolesw ith methyleneindolinones represent one of the most efficient routes to de novo construct the 3,3'-pyrrolidonyl spirooxindole scaffold (Scheme 1, path a).[2c, 4, 5] The first example was reported by the Gong group in 2009, disclosing ac hiral Brønsted acid-catalysed [3+ +2] cycloadditiono fi ns itu generatedi mino esters with methyleneindolinones.[4a] In addition, Waldmann and co-workers developed ac hiral copper-catalysed [3+ +2] cycloaddition of methyleneindolinones with N 2 -1,3-dipoles.[5a]Many other robust catalysts ystems with chiral organic molecules [4] or chiral Lewis acids [5] have been also established by Wang, Arai and Yamanaka, as well as by many other groups.G iven the fundamental significance of diversity-oriented synthesis, [6] we herein discloseapalladium-catalysed asymmetric [3+ +2] cycloaddition reactiono fP d-containing N 1 -1,3-dipoles with methyleneindolinones. This cycloaddition provides ad ivergents ynthetic approach to functional group-enriched 3,3'-pyrrolidonyl spirooxindoles.…”

The Future of Catalysis by Chiral Lewis Acids

“…Reaction occurs with preformed ylides (e. g., Scheme 17) [74] or those formed in situ by coordination with the imine nitrogen and base removal of an alpha-hydrogen (e. g., Scheme 18) [75]. Variations of base-stabilizing substituents, dipolarophile, and ligated catalyst give enormous breadth to this transformation [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91], and enantioselectivities greater than 90% ee are generally achieved.…”

Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition

“…[8] However,m ost of the synthesis methods yield racemic compounds,and general methods for the asymmetric catalytic synthesis of functionalized tropanes are in high demand. [9] The1 ,3-dipolar cycloaddition of azomethine ylides [10][11][12] with different olefins gives efficient access to pyrrolidines,w hich define the characteristic fragment core structure of numerous alkaloids. [7c, 13] We envisioned that the combination of this cycloaddition with racemic tropanes (readily accessible by means of a[ 5 + +2] cycloaddition of 3-oxidopyrylium betaines [14,15] )w ith alkenes could provide ap owerful approach to complex polycyclicn atural product inspired architectures incorporating both the tropane and pyrrolidine fragment structures.…”