Catalyst-Controlled Diastereoselectivity Switch in the Asymmetric [3 + 2] Annulation of Isatin-Derived MBH Carbonates and 5-Alkenylthiazol-4(5H)-ones

Abstract

Exploration of the diastereodivergent synthesis of spirocyclic oxindoles has been challenging. Herein we report asymmetric [3 + 2] annulations of isatin-derived Morita–Baylis–Hillman (MBH) carbonates and 5-alkenylthiazol-4­(5H)-ones. Interestingly, two different chiral catalysts, amide-phosphine and 4-dimethylaminopyridine (DMAP)-thiourea, could lead to two kinds of diastereomeric dispiro oxindoles with three contiguous stereogenic centers. The hexafluoroisopropanol (HFIP) additive plays a vital role in accelerating the reaction and tuning the diastereoselectivity. Moreover, both annulation adducts could be further converted to structurally diverse spirooxindoles.

Recent Advances in Nucleophilic Lewis Base‐Catalyzed Cycloadditions for Synthesis of Spirooxindoles

“…In 2021, Wang and coworkers reported catalyst-control, Lewis base-catalyzed diastereodivergent [3 + 2] cycloaddition of isatin-derived Morita-Baylis-Hillman (MBH) carbonates and 5alkenylthiazol-4(5H)-ones (Scheme 34). [58] In this reaction, two different chiral nucleophilic Lewis base catalysts, amide-phosphine 144 and 4-dimethylaminopyridine (DMAP)-thiourea 146, could lead to two kinds of diastereomeric spirooxindoles in high yields with excellent enantioselectivities. The experiment result showed that additive HFIP (hexaflfluoroisopropanol) could accelerate the reaction and tun the diastereoselectivity.…”

Recent Advances in Lewis Base‐Catalysed Chemo‐, Diastereo‐ and Enantiodivergent Reactions of Electron‐Deficient Olefins and Alkynes

“…More Recently, Wang, Tian and Tang reported an asymmetric (3 + 2) annulations of isatin-derived Morita-Baylis-Hillman (MBH) carbonates and 5-alkenylthiazol-4(5H)-ones, producing two diastereomeric dispiro oxindoles 139 and 140 in good yields and enantioselectivities. [46] The authors found that two different Lewis base catalyst, amide-phosphine 137 and 4dimethylaminopyridine (DMAP)-thiourea 138, could realize full control of diastereoselectivities. Further study suggested that the hexafluoroisopropanol (HFIP) additive plays a vital role in accelerating the reactions and tuning the diastereoselectivities (Scheme 30).…”

Substrate-Controlled Diversity-Oriented Synthesis of Novel Polycyclic Frameworks via [4 + 2] and [3 + 2] Annulations of Ninhydrin-Derived MBH Adducts with 3,4-Dihydroisoquinolines

“…Among them, the Morita-Baylis-Hillman (MBH) adducts and their derivatives have been extensively explored due to their multifunctional features, and applied as versatile synthons in diverse annulation reactions, mostly for the construction of polycyclic frameworks via cycloaddition with a large variety dipolarophiles [28][29][30][31][32][33]. In particular, isatins or aldehydes-derived MBH carbonates can act as valuable C1, C2, C3, or C4 synthons, which in situ generated zwitterionic allylic ylide species under Lewis base catalysis [34][35][36][37] or π-allyl metal complexes [38][39][40][41][42][43][44][45], to exhibit universal building blocks for the construction of multifunctional and potentially biologically active ring structures via various [3 + n] [46][47][48][49][50][51][52][53], [2 + n] [54][55][56][57][58], [1 + n] [59][60][61][62][63] annulation reactions. As a result, in the past few years, these annulations of employing the isatin or aldehydes-derived MBH carbonates as substrates have evolved into an extremely vibrant research area and achieved great progress and developments.…”