Organocatalytic Regio- and Enantioselective [3 + 2]-Annulations of Ninhydrin-Derived Morita–Baylis–Hillman Carbonates with 3-Methyleneoxindoles

Abstract

A type of Morita−Baylis−Hillman (MBH) carbonates has been developed from ninhydrin. These MBH carbonates have been successfully employed as 3C-synthons in the organocatalytic asymmetric [3 + 2]-annulations of the isatin-derived electron-deficient olefins, affording structurally diverse spirooxindoles in high yield with excellent stereoselectivity. In particular, the regioselectivity of MBH carbonates was controlled by the reaction partner, 3-methyleneoxindoles with carbonyl groups (R = ArCO), affording β-selective products and 3-methyleneoxindoles with ester groups (R = CO 2 Me) furnishing γ-selective products. The representative scale-up reactions and transformation of product were examined. The reaction mechanism was expounded by control experiments.

Synthesis of 1,3,5-trisubstituted pyrazolesvia1,3-dipolar cycloaddition of nitrile imines with ninhydrin-derived Morita–Baylis–Hillman carbonates

“…Dried solvents and liquid reagents were transferred by oven-dried syringes. The ninhydrin-derived Morita–Baylis–Hillman carbonates 1 13 and hydrazonyl chloride 2 15 were prepared according to the literature procedures.…”

“…The range of methodologies that have employed MBH carbonates from aldehydes or isatins as the substrates is extremely extensive, 12 whereas the analogous MBH carbonates from ninhydrin have been less explored. 13 Therefore, the development of structurally diverse MBH carbonates is always in great demand. Herein, we would like to present an effective process to furnish 1,3,5-trisubstituted pyrazoles via [3 + 2] cycloaddition strategy from ninhydrin-derived MBH carbonates with nitrilimines generated in situ from hydrazonyl halide (Scheme 1e).…”

Expeditious entry into carbocyclic and heterocyclic spirooxindoles

“…The reaction produces a dispiro compound with spiroindane-1,3-dione and spirooxindole moieties 157 (Scheme 87). 70 Substituents present on 5q determine the regioselectivity of MBH carbonates as 3-methyleneoxindoles bearing carbonyl group 5qa (R = COAr) provides β-selectivity affording 157a , while ester group 5qb (R = CO 2 Me) provides β′-selectivity affording 157b . The reaction worked well with substituents with different electronic effects and does not have any steric hindrance impact.…”

Dearomative [4 + 2] cycloaddition of 3‐nitroindoles with ortho‐amino Morita−Baylis−Hillman carbonates to forge indole‐fused quinolines

“…On the other hand, Morita−Baylis−Hillman (MBH) carbonates are versatile synthons [28–30], including C1 , C2 , C3 , C4 , C5 , and C6 synthons, to display enormous synthetic potential in constructing various cyclic compounds via [2 + 1] [31, 32], [4 + 1] [33], [3 + n] (n = 2, 3, 4, 6) [34–38], [4 + 2] [39–42], [5 + 4] [43], and [6 + 2] [44] annulations. In particular, the o‐ acylamino‐aryl MBH carbonates that added a nucleophilic site provided more challenges and opportunities for organic synthesis that could engage [4 + 2] annulations or [6 + 2] annulations or classic [3 + 2] annulations [42].…”