One-Pot Synthesis of Indolizines via Sequential Rhodium-Catalyzed [2 + 1]-Cyclopropanation, Palladium-Catalyzed Ring Expansion, and Oxidation Reactions from Pyridotriazoles and 1,3-Dienes

Abstract

An efficient, one-pot synthetic method for producing functionalized indolizine derivatives was developed via a Rh-catalyzed [2 + 1]-cyclopropanation, Pd-catalyzed ring expansion, and subsequent oxidation using manganese dioxide from pyridotriazoles and 1,3-dienes.

Rhodium(II)‐Catalyzed Formal [4+1]‐Cycloaddition of Pyridotriazoles and Propargyl Alcohols: Synthesis of 2,5‐Dihydrofurans

“…In the last decade, Gevorgyan and others have reported a variety of cycloaddition reactions with pyridotriazole as α‐pyridyl carbene precursor . In most of these transformations, pyridotriazole served as a three‐element “N−C−C” synthon in [3+2]‐cycloaddition with alkynes (Scheme b), alkenes, nitriles, amides . However, no cyclization reaction with this species as a “one‐C” building block has been disclosed .…”

“…[14] Notably, in these advances, the compatibility of the catalysts with corresponding substrates is essential in the development of selective catalytic transformations. [16][17][18][19][20] In most of these transformations, pyridotriazole served as a three-element "NÀCÀC" synthon in [3 + 2]-cycloaddition with alkynes (Scheme 1b), [16] alkenes, [18] nitriles, [19] amides. [15] In the last decade, Gevorgyan and others have reported a variety of cycloaddition reactions with pyridotriazole as a-pyridyl carbene precursor.…”

Transition Metal-Catalyzed Selective Carbon–Carbon Bond Cleavage of Vinylcyclopropanes in Cycloaddition Reactions

“…In 2017, the Lee group reported an efficient, one-pot synthetic method that used pyridotriazoles 1 and 1,3-dienes 2 for the preparation of functionalized indolizine derivatives 5 (Scheme 3). 24 This tandem three-step process involves a Rh(II)-catalyzed cyclopropanation of 1,3-dienes, a Pd(0)-catalyzed ring expansion of in situ generated VCPs 3 through addition of the nitrogen nucleophile to the Pd-π-allyl, and subsequent oxidation by MnO 2 to afford indolizine compounds 5 in good yields. In 2019, the Hawkins group reported an efficient synthesis of benzannulated 6,5-spiroketals 9 from vinyl 1,1-diacylcyclopropanes 7 (Scheme 4).…”

Novel Tandem Three Consecutive Reactions: Aza-Wittig, Imine Condensation and Electrophilic Aromatic Substitution Strategy to Indolizine Synthesis

“…General procedure for the synthesis of indolizine compounds A mixture of 0.1 mmol of the iminophosphorane intermediate (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) (Scheme 1 and Table 1) and 0.1 mmol of the corresponding 2,3-thiophenecarboxaldehyde in 2 mL of xylene was refluxed for 48 h. The mixture was allowed to reach the room temperature and then purified by column chromatography (silica gel 70 -230 mesh) yielding solids in all cases (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

“…In particular, the development of new routes to achieve both, new and improved synthesis of these products, is in constant demand [6] [7] [8]. In this context, synthesis of indolizines compounds has been reported using ingenious and sophisticated pyridine starting strategies [9]- [19].…”