Preparation of Annulated Nitrogen-Containing Heterocycles via a One-Pot Palladium-Catalyzed Alkylation/Direct Arylation Sequence

Abstract

[reaction: see text] A palladium-catalyzed/norbornene-mediated sequential coupling reaction involving an aromatic sp(2) C-H functionalization as the key step is described, in which an alkyl-aryl bond and an aryl-heteroaryl bond are formed in one pot. A variety of highly substituted six- and seven-membered annulated pyrroles and pyrazoles were synthesized in a one-step process in good yields from readily accessible N-bromoalkyl pyrroles or pyrazoles and aryl iodides.

Direct transition metal-catalyzed functionalization of heteroaromatic compounds

“…56 Further, Lautens applied this methodology for annulation of pyrroles and pyrazoles 96 (Scheme 39). 57 Similar to the previous example, 56 this one-pot protocol was proven to be very effective towards formation of a number of fused six-and seven-membered ring systems. 57 Very recently, Lautens disclosed the synthesis of polycyclic furans and thiophenes 101 via an analogous one-pot alkylation-intramolecular heteroarylation sequence (Scheme 40).…”

“…57 Similar to the previous example, 56 this one-pot protocol was proven to be very effective towards formation of a number of fused six-and seven-membered ring systems. 57 Very recently, Lautens disclosed the synthesis of polycyclic furans and thiophenes 101 via an analogous one-pot alkylation-intramolecular heteroarylation sequence (Scheme 40). 58 It was found that the reaction provides good to excellent yields of oxygen and sulfurcontaining polycyclic products 101 only when electron-deficient aryl iodides are used.…”

Catalytic C–C coupling through C–H arylation of arenes or heteroarenes

“…Pd-catalyzed domino reactions involving ortho alkylation of aryl iodides and direct arylation of indoles [42], pyrroles [43], thiophenes and furans [44] to produce polycyclic heterocycles have been described by Lautens' group. For example the sevenmembered annulated ring product of Scheme 8 was obtained in 89% yield.…”

Sequentially Palladium-Catalyzed Processes in One-Pot Syntheses of Heterocycles

“…Two sets of reaction conditions were optimized for regioselective one-pot syntheses The Lautens group has further developed Catellani's norbornene-mediated Pd-catalyzed ortho-alkylation of iodo arenes under Heck conditions [131] and published an efficient methodology accessing functionalized polycyclic heterocycles by employing a norbornene-mediated, palladium-catalyzed tandem alkylation direct arylation sequence in a one-pot fashion [132][133][134][135]. After oxidative addition of the palladium(0) species to the employed iodoarene a carbopalladation of norbornene precedes the sp 2 CH activation that enables the alkylation.…”

“…Reductive elimination of the postulated intermediary palladium(IV) complex followed by dismissal of norbornene gives rise to a second CH activation that results in the heteroannulated pyrroles 42 (Scheme 28, Table 13). Following this methodology, six-and seven-membered annulated pyrroles and pyrazoles [132], polycyclic thiophenes and furans [133], annulated 2-H-indazoles and 1,2,3-and 1,2,4-triazoles [134], and, even more remarkable, sterically hindered bi-and tricyclic benzonitriles [135] have been prepared. Scheme 28.…”