David Madec

Aryl sulfoxides from allyl sulfoxides via [2,3]-sigmatropic rearrangement and domino Pd-catalyzed generation/arylation of sulfenate anions.

Allylic sulfoxides, via [2,3]-sigmatropic rearrangement and oxidative addition of the resulting allylic sulfenate esters to Pd(0), are found to be excellent precursors of sulfenate anions. This hitherto unknown reactivity is applied in a new Pd(0)-catalyzed domino sequence involving sulfenate anion generation followed by arylation to afford aryl sulfoxides.

New Picropodophyllin Analogs via Palladium-Catalyzed Allylic Alkylation-Hiyama Cross-Coupling Sequences

Unsaturated malonyl esters underwent Pd-catalyzed intramolecular allylic alkylation to give 4-vinyl-substituted gamma-lactones. In contrast to the formerly studied cyclization of malonamides, this reaction could be achieved only with a substrate incorporating a suitably positioned silicon moiety, which directs the ionization toward the desired eta(3)-allylpalladium complex. The resulting 4-[dimethyl-(2-thienyl)silylvinyl]lactone could be subsequently engaged into Hiyama couplings with various iodoarenes, to give the corresponding 4-(alpha-styryl)-gamma-lactones. The use of a specifically substituted iodoarene generated an advanced tetracyclic lactone intermediate incorporating rings A-D of lignans belonging to the podophyllotoxin family. Subsequent electrophilic aromatic substitution with a variety of electron-rich arenes afforded the target picropodophyllin analogs.

A smart palladium catalyst in ionic liquid for tandem processes

New catalytic systems based on in situ and preformed palladium nanoparticles in ionic liquids (characterised by TEM) starting from palladium acetate or dipalladiumtris(dibenzylideneacetone) have been applied in the synthesis of 4-phenylbutan-2-one (II), a model compound for the preparation of fragrances. Imidazolium-based ionic liquid containing a methyl hydrogenophosphonate anion leads to an efficient Pd-catalyzed tandem coupling/reduction process, taking advantage of the multi-role of this solvent (nanoparticles stabiliser, base, hydrogen transfer agent). The influence of the mono-phosphine ligands (1-3) on the catalyst has been evaluated, showing that the ligand-free palladium system turns into the most appropriate for the formation of II using Pd(OAc)(2) as precursor. Fine-tuning conditions involved in this multi-parameter process have led us to propose a plausible mechanism based on the hydrogen transfer coming from the methyl hydrogenophosphonate anion.

Synthesis of γ-lactams and γ-lactones via intramolecular Pd-catalyzed allylic alkylations.

CONSPECTUS: Lactones and lactams are a well-known class of natural products and can be used as building blocks in organic synthesis. In addition, they can be found in many natural sources and synthetic drugs and have a broad range of biological or odorant properties. Chemists can create these useful compounds through palladium catalysis, which is a highly efficient tool for organic synthesis and is conveniently functional group tolerant. In this Account, we describe our work over the past 15 years in intramolecular Pd-catalyzed allylations where we have tethered the nucleophile and the electrophile by either an amide or an ester moiety, to produce γ-lactams and γ-lactones. We discuss in detail how the nature of the heteroatom tether influences the regioselectivity of the reaction. For example, a ketone [-C(O)CH2-] tether leads to mixtures of 5-exo and 7-endo cyclization products, while ester or amide [-C(O)X-] tethers afford sole 5-exo products. However, in the case of X = O, we were required to overcome two issues in the synthesis of γ-lactones. First of all, the tethering ester function can compete with the allylic leaving group in the oxidative addition to the Pd(0) center. Second, in this case, the proportion of the conformers that have a suitable geometry for cyclization is very low. When we insert a juxtaposed silyl group on the allyl fragment, the molecule can undergo oxidative addition and functionalization of the lactone via Hiyama cross-coupling. We also performed DFT calculations on these systems, which allowed us to better understand the behavior of [-C(O)X-] and [-C(O)CH2-] tethers. Computations also let us rationalize the different reactivities that we observed as a function of the geometry (Z or E) of the starting substrates. In addition, we were able to synthesize natural products or analogs (α-kainic acid, isoretronecanol, and picropodophyllin). We could turn these allylation reactions into asymmetric transformations and incorporate them into domino sequences. Thus, an allylation/Mizoroki-Heck sequence allowed us to straightforwardly access an aza-analog of picropodophyllin, as well as reach the lysergic acid backbone. Finally, we found that through carbopalladation of allenes, we could efficiently synthesize the key η(3)-allylpalladium intermediates that were then ready for allylation reactions.

Palladium-catalyzed pseudo-domino cyclizations: An easy entry toward polycondensed pyrrolidone derivatives

Abstract A new type I palladium-catalyzed pseudo-domino process is developed, in which a single Pd-based catalytic system promotes two mechanistically unrelated, sequential catalytic cycles in chronologically distinct order. Suitable precursors undergo an allylic alkylation and a Heck coupling in sequence, affording polycondensed pyrrolidone derivatives. Depending on the starting precursors, intra/inter or doubly intramolecular processes can be obtained. The allylic alkylation process takes place always very smoothly. On the other hand, the Heck coupling turns out to be rather difficult either when the process is intermolecular, or when an intramolecular process generates polycondensed structures featuring three fused bonds connected to a common carbon atom. In such difficult cases, use of the Herrmann–Beller phosphapalladacycle allowed to catalyze the coupling. This study demonstrates also that allylic alkylations can be catalyzed by the Herrmann–Beller phosphapalladacycle.

A Bis‐Sulfonyl O,C,O Aryl Pincer Ligand and its Tin(II) Complex: Synthesis, Structural Studies, and DFT Calculations

The efficiency of the deprotonated aryl bis-sulfone [2,6-{(p-tolyl)SO2}2C6H3](-) as an O,C,O-coordinating pincer-type ligand was described. The bis-sulfone precursor was synthesized using a straightforward palladium-catalyzed cross-coupling reaction. As a result of directed ortho metalation (DoM) through sulfonyl groups, a selective lithiation of the aryl group was achieved and the corresponding carbanion was isolated and its structure determined by single-crystal X-ray diffraction analysis. A heteroleptic tin(II) complex has been prepared by a nucleophilic substitution reaction. Crystallographic analysis and DFT calculations indicate that the bis-sulfonyl moiety acts as a new O,C,O-coordinating pincer-type ligand with intramolecular S=O coordination to a tin(II) center. The cis form with the two nonbonded oxygen atoms of the sulfonyl groups on the same side is preferentially obtained.

HIGHLY REGIOSELECTIVE PALLADIUM-CATALYZED CONDENSATION OF TERMINAL ACETYLENES WITH 2,5-DIIODOBENZOIC ACID

Abstract Palladium-catalyzed coupling reactions between terminal alkynes and 2,5-diiodobenzoic acid have been shown to be highly regioselective, giving a rapid and efficient route for the synthesis of disymmetric 2,5-bis ethynyl benzoic acid derivatives.

Functionalized 2,3-dihydrofurans via palladium-catalyzed oxyarylation of α-allyl-β-ketoesters

The palladium-catalyzed reaction of (hetero)aryl bromides, chlorides, and nonaflates with α-allyl-β-ketoesters provides ready efficient access to functionalized 2,3-dihydrofurans. The reaction tolerates several useful substituents including chloro, fluoro, ether, ketone, ester, cyano, and nitro groups.

Bis‐Sulfonyl O,C,O‐Chelated Metallylenes (Ge, Sn) as Adjustable Ligands for Iron and Tungsten Complexes

The synthesis and characterization of an E2 CE2 bis-sulfonyl aryl pincer ligand and its efficiency for the stabilization of compounds containing low-valent Group 14 elements (Ge and Sn) are reported. Complexation reaction of these metallylenes with iron or tungsten complexes resulted in the modulation of the oxygen atoms of the sulfonyl groups implicated in the stabilization of the Group 14 elements, demonstrating the original adjustable character of the bis-sulfonyl O2 S-C-SO2 aryl pincer.

Germylene–sulfoxide as a potential hemilabile ligand: application in coordination chemistry

We describe here the synthesis of heteroleptic organogermylenes containing a sulfoxide donor function for their application in coordination chemistry. While complexation reaction with [W(cod)(CO)4] and [Mo(nbd)(CO)4] afforded bis(germanium)(ii) transition-metal complexes, a bidentate complex coordinated by germanium(ii) and the oxygen atom of the sulfinyl group was obtained from [Ru(PPh3)3Cl2].