title: A palladium iodide-catalyzed carbonylative approach to functionalized pyrrole derivatives.
abstract: A novel and convenient approach to functionalized pyrroles is presented, based on Pd-catalyzed oxidative heterocyclization-alkoxycarbonylation of readily available N-Boc-1-amino-3-yn-2-ols. Reactions were carried out in alcoholic solvents at 80-100 °C and under 20 atm (at 25 °C) of a 4:1 mixture of CO-air, in the presence of the PdI(2)-KI catalytic system (2-5 mol % of PdI(2), KI/PdI(2) molar ratio = 10). In the case of N-Boc-1-amino-3-yn-2-ols 3, bearing alkyl or aryl substituents, the carbonylation reaction led to a mixture of Boc-protected and N-unsubstituted pyrrole-3-carboxylic esters 4 and 5, respectively. This mixture could be conveniently and quantitatively converted into deprotected pyrrole-3-carboxylic esters 5 by a simple basic treatment. In the case of diastereomeric (3RS,4RS)- and (3RS,4SR)-N-Boc-3-amino-2-methyldec-5-yn-4-ol (syn-3f and anti-3f, respectively, whose relative configuration was determined by X-ray crystallographic analysis), no particular difference was observed in the reactivity of the two diastereomers between them and with respect to the diastereomeric mixture (3S,4S) + (3S,4R). Interestingly, N-Boc-2-alkynyl-1-amino-3-yn-2-ols 6, bearing an additional alkynyl substituent α to the hydroxyl group, spontaneously underwent N-deprotection under the reaction conditions and regioselective water addition to the alkynyl group at C-3 of the corresponding pyrrole-3-carboxylic ester derivative, thus directly affording highly functionalized pyrrole derivatives 7 in one step. In a similar manner, a novel functionalized dihydropyrrolizine derivative 9 was directly synthesized starting from (S)-7-(pyrrolidin-2-yl)trideca-5,8-diyn-7-ol 8.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende (CS), Italy. b.gabriele@unical.it
authors.forename: Bartolo
authors.initials: B
authors.lastname: Gabriele
authors.forename: Lucia
authors.initials: L
authors.lastname: Veltri
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mancuso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Salerno
authors.forename: Sabino
authors.initials: S
authors.lastname: Maggi
authors.forename: Brunella Maria
authors.initials: BM
authors.lastname: Aresta
mesh_terms: D002384:Catalysis; D003500:Cyclization; D007454:Iodides / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D007454:Iodides; D011758:Pyrroles; D010165:Palladium