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

Abstract

Substrate-controlled diversity-oriented synthesis of polycyclic frameworks via [4 + 2] and [3 + 2] annulations between ninhydrin-derived Morita–Baylis–Hillman (MBH) adducts and 3,4-dihydroisoquinolines under similar reaction conditions have been developed. The reaction provides diversity-oriented synthesis of a series of novel and structurally complex spiro multi heterocyclic skeletons in good yields (up to 87% and 90%, respectively) with excellent diastereoselectivities (up to >25:1 dr). In particular, the switchable [4 + 2] and [3 + 2] annulation reactions are controlled by tuning the hydroxyl protecting group on the ninhydrin-derived MBH adduct to deliver structural diverse spiro[indene-2,2′-[1,3]oxazino[2,3-a]isoquinoline] and spiro[indene-2,1′-pyrrolo[2,1-a]isoquinoline], respectively. Furthermore, the relative configuration and chemical structure of two kinds of cycloadducts were confirmed through X-ray diffraction analysis.

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

“…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]. In connection with our continuous efforts on the annulation of MBH carbonates [38,42,[45][46][47][48], herein, we are interested in presenting organocatalytic dearomative [4 + 2] cycloaddition to efficiently construct functionalized tetrahydro-5H-indolo [2,3-b]quinoline scaffolds incorporating tetrahydroquinoline and indole motifs under mild reaction conditions without metal catalysts (Scheme 1D), which are structurally interesting cores with potential in natural product synthesis and drug discovery. At the outset, we chose the o-acylamino-aryl MBH carbonate 1a and 3-nitroindole 2a as the model substrates to optimize the reaction conditions.…”