Phosphine‐Catalyzed (3+2) Annulation of Isoindigos with Allenes: Enantioselective Formation of Two Vicinal Quaternary Stereogenic Centers

Abstract

Construction of contiguous all-carbon quaternary stereogenic centers is al ong-standing challenge in synthetic organic chemistry.I nt his report, ap hosphine-catalyzed enantioselective (3+ +2) annulation reaction between allenes and isoindigos,c ontaining either two identical or different oxindole moieties,i si ntroduced as ap owerfuls trategy for the construction of spirocyclic bisindoline alkaloid core structures. The reported reactions feature high chemical yields,e xcellent enantioselectivities,a nd very good regioselectivities,a nd are highly useful for creating structurally challenging bisindoline natural products. Scheme 1. Tetrasubstituted activateda lkenes are challenging substrates in phosphine-catalyzed (3+ +2) annulation reactions with allenes.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Catalytic enantioselective construction of vicinal quaternary carbon stereocenters

“…In 2019, Mei and Lu reported a chiral phosphine 140-catalyzed enantioselective [3 + 2] annulation of allenic esters 139 with isoindigos 137, bearing two identical oxindole moieties, for the synthesis of dimeric spirocyclic bisindolines 141 with high yields and excellent ee (Scheme 27). 81 The reaction of unsymmetric isoindigos 138 was also performed. Using an electronic/stericdifferentiation strategy, the structurally distinct spirocyclic molecules 142 were obtained with high yield and excellent ee.…”

All-carbon [3 + 2] cycloaddition in natural product synthesis

“…In 2019, Lu and co-workers disclosed a novel chiral-phosphine-catalyzed enantioselective [3 + 2] annulation of allenes and isoindigos to give an enantioenriched annulation adduct bearing vicinal quaternary stereocenters [ 46 ] ( Scheme 7 ). Both symmetric and unsymmetric isoindigos can undergo enantioselective [3 + 2] annulation with an allene and produced a chiral adduct with high yield and high ee value.…”

“… (A) Phosphine-catalyzed [3 + 2] annulation of unsymmetric isoindigo 100 with allene in the preparation of spiro adduct 103 [ 46 ]. (B) The proposed catalytic cycle.…”

“…In the same work, Lu and co-workers applied the enantioselective [3 + 2] annulation to complete the formal synthesis of (−)-ditryptophenaline ( 12 ) [ 46 ] ( Scheme 7 ). The synthesis began with the catalytic asymmetric [3 + 2] annulation of symmetric isoindigo 104 and allene 101 with chiral phosphine catalyst 102 to give spirocyclic adduct 105 in 93% yield with 99% ee.…”

Stereo‐ and Regioselective Construction of Spirooxindoles Having Continuous Spiral Rings via Asymmetric [3+2] Cyclization of 3‐Isothiocyanato Oxindoles with Thioaurone Derivatives

“…[ 8 ] In 2019, Lu's group reported a l ‐Thr derived phosphine‐catalyzed enantioselective [3+2] annulation reaction between allenes and isoindigos (Scheme 1d). [ 9 ] In 2014, Shi's group envisaged a chiral phosphoric acid‐catalyzed three‐component cascade Michael/Pictet–Spengler reactions of isatin‐derived 3‐indolylmethanols, isatins, and amino‐ester (Scheme 1e). [ 10 ] It is well known that 3‐isothiocyanato oxindole is a widely used isatin derivative for the construction of spirooxindoles.…”