Ludivine Jean-Gérard

Palladium-Catalyzed β Arylation of Carboxylic Esters†

The direct functionalization of C H bonds is an atomand step-economical alternative to more traditional synthetic methods based on functional-group transformations, which often require multistep sequences. In particular, transitionmetal catalysis has emerged as a powerful tool for the functionalization of otherwise unreactive C(sp) H and C(sp) H bonds. These advances have enabled the construction of a variety of carbon–carbon and carbon–heteroatom bonds with great efficiency and selectivity, even in structurally complex organic molecules. In this context, we previously investigated the intramolecular arylation of unactivated C(sp) H bonds under palladium(0) catalysis. Intermolecular C(sp) H arylation reactions have also been developed through the use of palladium(II) or palladium(0) catalysis and the assistance of a coordinating group, such as a carbonyl group (Scheme 1a). This group directs arylation in the b position through the formation of a chelated palladium homoenolate. The palladium(0)-catalyzed C H arylation a to an electron-withdrawing functional group (Scheme 1b, path 1) has also been established as a powerful method for the construction of C(sp) C(sp) bonds. An enantioselective reaction is also possible with a chiral catalyst. This reaction takes advantage of the acidity of the C H bond a to the electron-withdrawing group—in general a carbonyl group— to generate a palladium enolate, which is converted into the a-arylated product by reductive elimination. Herein, we describe a diversion from this mechanism and the development of a straightforward and conceptually new b-C H arylation method (Scheme 1b, path 2). Because this new type of b arylation is related mechanistically to a arylation, it is complementary to directing-group-controlled b arylation reactions. In this regard, it presents a few interesting features; for example, simple carboxylic esters can be used as substrates at mild temperatures, and no polyarylation products are formed. We also describe the proof of concept of an enantioselective variant with a chiral catalyst and propose a reaction mechanism on the basis of DFT calculations. Our initial studies focused on the palladium-catalyzed arylation of the lithium enolate of tert-butyl isobutyrate (2 a) with ortho-, meta-, and para-fluorobromobenzene (1a–c ; Table 1; the lithium enolate was formed in situ from 2a and lithium dicyclohexylamide (Cy2NLi)). [8] The palladium catalyst was composed of tris(dibenzylideneacetone)dipalladium(0) ([Pd2(dba)3]) and 2-dicyclohexylphosphanyl-2’(N,N-dimethylamino)biphenyl (davephos). The reaction of the lithium enolate of 2a with paraand meta-fluorobromobenzene in toluene at 28 8C gave an approximately 1:1 mixture of a-arylation (compounds 3a,b) and b-arylation products (compounds 4a,b ; Table 1, entries 1 and 2). In contrast, the reaction with ortho-fluorobromobenzene (1c) gave only the b-arylation product 4 c, which was isolated in 63% yield (Table 1, entry 3). Similarly, the reaction of methyl isobutyrate 2b with 1c gave only the b-arylation product 4d (Table 1, entry 4). A slightly higher temperature (50 8C) was required for complete conversion in the reaction of bromide 1c with ester 2a than for other reactions, and the product 4c Scheme 1. a) Directing-group strategy for the palladium-catalyzed b arylation of carbonyl compounds. b) Palladium-catalyzed a and b arylation of enolates generated in situ.

Rational investigations in the ring opening of cyclic carbonates by amines

Non-isocyanate polyurethanes (NIPUs) constitute a promising alternative for more classical polyurethanes (PUs) as they may display mechanical properties that can match those of PUs and their synthesis does not involve the use of toxic isocyanates. Yet, because of the lower reactivity of carbonates versus isocyanates, the synthesis of NIPUs is not straightforward and generally requires the use of a catalyst. Recently, several groups have reported on the use of different ranges of catalysts for promoting the nucleophilic attack of the amine on the carbonate. However, many of these studies involve the use of highly reactive amine and/or carbonate proscribing a complete panorama of the potentialities of the reaction. Herein, we propose a rational study of the catalyzed aminolysis of four representative cyclic carbonates that reveals that the thiourea organocatalyst 1 outperforms in many aspects, classical inorganic or other organic catalysts.

Urea- and Thiourea-Catalyzed Aminolysis of Carbonates.

The aminolysis of (poly)carbonates by (poly)amines provides access to non-isocyanate polyurethanes (NIPUs) that are toxic-reagent-free analogues of polyurethanes (PUs). Owing to their low reactivity, the ring opening of cyclic carbonates requires the use of a catalyst. Herein, we report that the more available and cheaper ureas could advantageously be used for catalyzing the formation of NIPUs at the expense of the thiourea analogues. In addition, we demonstrate a medium-range pKa of the (thio)urea and an unqeual substitution pattern is critical for controlling the efficiency of the carbonate opening.

Experimental and Theoretical Investigations of the Stereoselective Synthesis of P‐Stereogenic Phosphine Oxides

An efficient enantioselective strategy for the synthesis of variously substituted phosphine oxides has been developed, incorporating the use of (1S,2S)-2-aminocyclohexanol as the chiral auxiliary. The method relies on three key steps: 1) Highly diastereoselective formation of P(V) oxazaphospholidine, rationalized by a theoretical study; 2) highly diastereoselective ring-opening of the oxazaphospholidine oxide with organometallic reagents that takes place with inversion of configuration at the P atom; 3) enantioselective synthesis of phosphine oxides by cleavage of the remaining P-O bond. Interestingly, the use of a P(III) phosphine precursor afforded a P-epimer oxazaphospholidine. Hence, the two enantiomeric phosphine oxides can be synthesized starting from either a P(V) or a P(III) phosphine precursor, which constitutes a clear advantage for the stereoselective synthesis of sterically hindered phosphine oxides.

Bis-triazolyl BODIPYs: a simple dye with strong red-light emission

The versatile synthesis of an unprecedented bis-triazolyl BODIPY dye displaying a high quantum yield even in water is described. X-ray diffraction analyses and NMR measurements demonstrate that the simultaneous presence of the two triazole moieties helps to re-enforce the rigidity of the BF2 complex.

Workshop on alternative solvents for synthesis, extraction, purification, and formulation (WAS 2017)

Comptes Rendus Chimie - In Press.Proof corrected by the author Available online since jeudi 17 mai 2018

Recent advances in the synthesis of [a]-benzo-fused BODIPY fluorophores”

This feature article summarizes the different strategies for the synthesis of [a]-benzo-fused BODIPYs that have been reported in the literature until 2018. These π-extended BODIPYs are promising fluorophores for bio-imaging and organic photovoltaic applications due to both their attractive photophysical properties in the near-infrared area and their higher (photo)chemical stability compared to conventional bis-styryl derivatives. The four main strategies described in this review can be used to access either directly the expected [a]-benzo-fused BODIPYs or through the di-/tetra-hydroisoindole.