Catalytic Asymmetric Formal [3+2] Cycloaddition of Azoalkenes with 3-Vinylindoles: Synthesis of 2,3-Dihydropyrroles

Abstract

Chiral phosphoric acid-catalyzed highly enantioselective formal [3 + 2] cycloaddition reaction of azoalkenes with 3-vinylindoles has been established. Under mild conditions, the projected cycloaddition proceeded smoothly, affording a variety of 2,3-dihydropyrroles in high yields and excellent enantioselectivities, and also in a diastereospecific manner. As opposed to the common 4-atom synthons in the previous literature reports, azoalkenes served as 3-atom synthons. Besides, the observed selectivity was supported by primary theoretical calculation. The unique chemistry of azoalkenes disclosed herein will empower asymmetric synthesis of nitrogen-containing ring structural motifs in a broader context.

Enantioselective and Diastereodivergent Synthesis of Spiroindolenines via Chiral Phosphoric Acid-Catalyzed Cycloaddition

“…Indeed, calculated data performed with a simplified phosphoric acid catalyst provide only qualitative insights. Refinement of transition states performed with real catalyst 1i (see Supporting Information, Table S1) using the cheaper STO-3G basis to account for the increased number of atoms led to a lowering of the ΔΔ G ⧧ to 3.2 kcal/mol. Such a value does again not exactly match the experimental ee values (56%), but this indicates a clear trend to support the new proposed mechanism.…”

Hetero-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies

“…A large number of new reviews [ 26 , 27 , 56 , 57 ] and original publications [ 31 , 58 , 59 , 60 , 61 , 62 ], which appeared in the last four years, demonstrates the growing interest in the chemistry of azoalkenes and their applications in hetero -Diels-Alder reactions. The presented study showed important mechanistic aspects and demonstrated that scarcely known 3,6-dihydro-2 H -1,3,4-thiadiazines can efficiently be prepared by regioselective hetero -Diels-Alder reactions of thioketones with in situ-generated azoalkenes, bearing an electron-withdrawing substituent at the terminal N-atom.…”

“…Numerous original publications appear regularly. In addition, very recent reports focused on asymmetric cycloaddition reactions with this type of hetero-dienes and a few of them can be cited as representative examples [ 28 , 29 , 30 , 31 ].…”

Application of 3-Alkyl-2-vinylindoles in Catalytic Asymmetric Dearomative (2+3) Cycloadditions

“…Vinylindoles, including 3-vinylindoles, 2-vinylindoles, − and other vinylindoles, have been recognized as versatile building blocks, and their related catalytic asymmetric reactions have shown great potential for the synthesis of structurally diverse chiral indole derivatives. Among them, 3-alkyl-2-vinylindoles belong to a class of highly active vinylindoles, and catalytic asymmetric reactions of 3-alkyl-2-vinylindoles have developed rapidly over the past decade. − …”