Metal-Free and Regioselective Synthesis of Functionalized α-Carbolines via [3 + 3] Annulation of Morita–Baylis–Hillman Acetates of Nitroalkenes with Iminoindolines

Abstract

A facile, metal-free method for the synthesis of substituted α-carbolines from secondary Morita–Baylis–Hillman (MBH) acetates of nitroalkenes is presented. The cascade reaction of MBH acetates with tosyliminoindolines occurs regioselectively to form various α-carbolines with a wide substrate scope. The reaction involves mild conditions, and the products are formed in high yields within a short reaction time. The amenability of the reaction to scale up and synthetic applications of the products have been demonstrated.

One‐Pot Regio‐ and Diastereoselective Synthesis of Tetrahydro‐α‐carbolines via Cascade Reactions of Iminoindolines with Morita‐Baylis‐Hillman Bromides of Nitroalkenes

“…Based on previous reports on the reactivity of MBH acetate [19][20][22][23] and bromide [21a] and the results observed, we propose a possible mechanism for the formation of tetrahydroα-carbolines 3 (Scheme 2). Base-assisted deprotonation of tosyliminoindoline 1 generates the corresponding stabilized tosyliminoindoline anion I.…”

“…[19][20][21][22] Recently, we reported the synthesis of a variety of α-carbolines via [3 + 3] annulation of secondary MBH acetates of nitroalkenes with tosyliminoindolines (Scheme 1b). [23] However, due to spontaneous aromatization, the above methodology (Scheme 1b) [23] was not suitable for the synthesis of tetrahydro-α-carbolines. Furthermore, a versatile functionality such as nitro group underwent elimination in the above case.…”

Design, Synthesis, and Biological Evaluation of Tetrahydro‐α‐carbolines as Akt1 Inhibitors That Inhibit Colorectal Cancer Cell Proliferation

“…On the other hand, MBH nitroallylic acetates are versatile electrophilic partners for synthesizing kinds of heterocycles and carbocycles [14] . Compared with well‐established cyclization with C,O [15] and C,C [16] dinucleophiles, the efficient annulation reaction of nitroallylic acetates with C,N ‐dinucleophile is limited explored (Figure 2b) [17] …”

Visible Light‐Mediated Reactions of β‐Nitroalkenes

“…Nitroalkenes also found a variety of applications in organic synthesis due to their multiple reactive sites and reactivity pattern [19] . Nitroalkenes and their derivatives react in various ways such as Michael addition, cyclizations, denitrative couplings, Morita‐Baylis‐Hillman and Rauhut‐Currier reactions, etc [20–33] . The diverse reactivity, easy availability, and bench‐stable solid property make nitroalkene a unique motif in organic synthesis.…”

“…[19] Nitroalkenes and their derivatives react in various ways such as Michael addition, cyclizations, denitrative couplings, Morita-Baylis-Hillman and Rauhut-Currier reactions, etc. [20][21][22][23][24][25][26][27][28][29][30][31][32][33] The diverse reactivity, easy availability, and bench-stable solid property make nitroalkene a unique motif in organic synthesis.…”