Amines as key building blocks in Pd-assisted multicomponent processes.

In the last few years, palladium-mediated three-component synthesis has emerged as an important synthetic methodology to gain access to nitrogen-containing structures. The latest developments in this area are discussed in this review.

Iodocyclization versus diiodination in the reaction of 3-alkynyl-4-methoxycoumarins with iodine: synthesis of 3-iodofuro[2,3-b]chromones.

The reaction of 3-alkynyl-4-methoxycoumarins with molecular iodine in chlorinated solvents allows access to 3-iodofurochromones in good to excellent yields as the result of a iodocyclization-demethylation process. Competitive diiodination of the coumarin acetylene moiety could be eliminated by simply performing the reactions in refluxing 1,2-dichloroethane, owing to the thermal instability of the resulting (E)-1,2-diiodoethenylcoumarins.

A modular sydnone cycloaddition/Suzuki-Miyaura cross-coupling strategy to unsymmetrical 3,5-bis(hetero)aromatic pyrazoles.

The [3 + 2] dipolar cycloaddition of 4-halosydnones with 1-haloalkynes opens a straightforward access to 3,5-dihalopyrazoles, valuable scaffolds for the elaboration of unsymmetrically 3,5-substituted pyrazole derivatives via site-selective Pd-catalyzed cross-coupling reactions. For instance, the flexible introduction of different (hetero)aryl substituents at the C-5 and C-3 positions of the PMP-protected pyrazole nucleus was achieved in a one-pot operation via sequential reactions with various boronic acids.

A Pd-catalyzed heteroannulation approach to 2,3-disubstituted furo[3,2-c]coumarins.

The Pd-catalyzed cyclofunctionalization of 3-alkynyl-4-methoxycoumarins with aryl halides resulted in the selective formation of 3-arylfuro[3,2-c]coumarins in lieu of the expected regioisomeric 3-arylfuro[2,3-b]chromones. A mechanism involving the linear to angular rearrangement of a Pd-containing furan intermediate was proposed.

Et3N-induced demethylation-annulation of 3-alkynyl-4-methoxy-2-pyridones and structurally related compounds in the synthesis of furan-fused heterocycles.

Various 3-iodo-4-methoxypyridin-2-ones and related pyrone and coumarin derivatives have been demonstrated as readily available precursors of 2-substituted furan-fused heterocycles by means of in situ sequential Sonogashira-acetylide coupling, dealkylation, and regioselective furan annulation reactions. A Et3N-induced S(N)2 process has been established that accounts for the dealkylation process.

Flexible strategy for differentially 3,5-disubstituted 4-oxypyridin-2(1H)-ones based on site-selective Pd-catalyzed cross-coupling reactions.

3,5-Dihalogeno-4-methoxy-N-methylpyridin-2(1H)-ones have been shown to undergo single Suzuki coupling reactions in a site-selective fashion. Monoarylations occur at the C-5 position preferentially, thus leaving the remaining C-3 halide free for further functionalization, to finally access differentially 3,5-disubstituted 2-pyridones. This two-step strategy has been applied to the elaboration of the 3-acyl-5-aryl-4-oxy-2-pyridone subunit that is prevalent in numerous bioactive natural products. [reaction: see text].

A synthetic entry to furo[2,3-b]pyridin-4(1H)-ones and related furoquinolinones via iodocyclization.

[reaction: see text] N-Methyl-4-alkoxy-3-alkynylpyridin-2(1H)-ones readily undergo iodine-promoted 5-endo-heteroannulation under mild conditions to 3-iodofuropyridinium triiodide salts in moderate to good yields. The latter may be dealkylated in situ upon exposure to an iodide anion to provide the corresponding 3-iodofuro[2,3-b]pyridin-4(1H)-ones. The same strategy applies to the formation of furo[2,3-b]quinolin-4(9H)-ones.

Selective Lewis acid catalyzed transformation (gamma-butyrolactone versus cyclopropane) of 2-methoxy-4-benzyltetrahydrofuran derivatives. Efficient synthesis of lignan lactones.

[reaction: see text]. A short synthesis of lactone lignans exploiting a three-component coupling strategy is presented using a new Lewis acid catalyzed ring-opening/cyclization reaction of 2-methoxytetrahydrofuran derivatives 4 leading to gamma-butyrolactones as a key step. By simply changing the reaction conditions, it was possible, from the same substrates 4, to obtain selectively cyclopropane derivatives.

Efficient syntheses of pterulone, pterulone B and related analogues.

An efficient synthesis of the three halogenated naturally occurring products, pterulone (2), pterulone B (3) and alcohol 5, and of a wide range of related unnatural analogues has been achieved starting from the two readily available 1-benzoxepine sulfonyl-containing intermediates 6a and 6b. The biological activities of pterulone and some of the synthesized analogues were tested against a wide spectrum of phytopathogenic fungi.

Palladium-mediated three-component synthesis of furo[2,3-b]pyridones by one-pot coupling of 3-iodopyridones, alkynes, and organic halides.

[reaction: see text] The one-pot assembly of 4-alkoxy-3-iodo-2-pyridones, terminal alkynes, and organic halides has been achieved by integration of two sequential palladium-mediated cross-coupling reactions--Sonogashira and Wacker-type heteroannulation processes--and subsequent deprotection of the alkoxy group to afford furo[2,3-b]pyridones.

Lewis acid-induced intramolecular Friedel-Crafts cyclization of 1,3-bis-exocyclic dienes. a new route to 4a-methyltetrahydrofluorenes.

[reaction: see text] An efficient new method for constructing the 4a-methyltetrahydrofluorene skeleton was achieved via Friedel-Crafts intramolecular cyclization of 1,3-bis-exocyclic dienes. This strategy offers a simple and promising method for accessing complex structures.

Unexpected isolation, and structural characterization, of a beta-hydrogen-containing sigma-alkylpalladium halide complex in the course of an intramolecular heck reaction. synthesis of polycyclic isoquinoline derivatives.

The isolation of a stable beta-hydrogen-containing R-PdLn-X complex (R = alkyl; X = halide) issued from a Heck reaction is reported together with some aspects of its reactivity.