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A decarboxylative Claisen condensation involving substituted malonic acid half oxyesters (SMAHOs) as pronucleophiles has been developed. The addition of their magnesium enolates to various acyl donors allows the synthesis of functionalized α-substituted β-keto esters in moderate to excellent yields (13–96%). In addition to acyl chlorides and acid anhydrides, these conditions proved efficient for the use of carboxylic acids as acylating agents, thus allowing to greatly extend the scope of this transformation (32 examples overall).

The use of mono-substituted malonic acid half oxyesters (SMAHOs) has been hampered by the sporadic references describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access to reagents bearing different substituents at the malonic position, including functionalized derivatives. On the other hand, the development of a monoesterification step of a substituted malonic acid derivative proved to be the best entry for diversity at the ester function, rather than the use of an intermediate Meldrum acid. Both these transformations are characterized by their simplicity and efficiency, allowing a straightforward access to SMAHOs from cheap starting materials.

The decarboxylative Mannich reaction between imines and substituted malonic acids half-oxyesters (SMAHOs) has been developed using 1,4-diazabicyclo[2.2.2]octane (DABCO) as an organocatalyst. The reaction proceeds under simple reaction conditions and tolerates a broad range of substrates, affording general access to β2,3-aminoesters, the syn diastereomer being the major one. An alternative multicomponent protocol has also been developed to increase the overall eco-compatibility of the process.

A straightforward and modular sequence for the synthesis of substituted spirocyclic tetrahydrofurans is described. The strategy relies on a reductive cobalt-catalyzed three-component reaction between a cyclic ketone, an acrylate, and a vinylic bromide followed by an intramolecular iodoetherification of the resulting γ-hydroxyalkene. Some functional group interconversions allowed the preparation of more varied spirocyclic compounds.

This investigation demonstrates the excellent photoinitiating properties of novel visible-light absorbing diphenylporphyrins (DPPs) for free-radical (FRP), cationic (CP) and thiol–ene polymerizations under visible LED irradiation (405 and 530 nm) at low intensities, under air or in laminate. Kinetics results on FRP and CP showed that DPPs are much more efficient photoinitiators than common Type II photosensitizers, i.e. camphorquinone or benzophenone. As confirmed by EPR and laser flash photolysis studies, DPPs play a dual role as an electron donor and in the H-abstraction reaction when combined with iodonium salt (Iod), N-methyldiethanol amine (MDEA) or thiol derivative, respectively.

We report for the first time the synthesis and use of a visible light-sensitive anthraquinone functional phthalocyanine (AQ-ZnPc) in combination with a suitable electron donor (methyldiethanol amin...

Multicomponent Mannich reactions through C-H bond activation are described. These transformations allowed for the straightforward generation of densely substituted benzylic and homo-benzylic amines in good yields. The reaction involves a reaction between two transient species: an organometallic species, generated by transition-metal-catalyzed sp2 or sp3 C-H bond activation and an in situ generated imine. The use of an acetal as an aldehyde surrogate was found essential for the reaction to proceed. The process could be successfully applied to RhIII -catalyzed sp2 C-H bond functionalization and extended to CuII -catalyzed sp3 C-H bond functionalization.

Inversions in the periselectivity of formal aza-Diels&ndash, Alder cycloadditions between &alpha, oxoketenes generated by a thermally-induced Wolff rearrangement and 1-azadienes were observed experimentally as a function of the &alpha, oxoketene and the 1-azadiene, as well as the reaction temperature and time. Some unexpected inversion in the diastereoselectivity was observed, too. These variations in selectivities were fully rationalized by computational modeling using density functional theory (DFT) methods.

Phenylzinc bromide enables a pseudo three-component reaction of methyl glutaconate and aromatic aldehydes. Unsaturated trisubstituted δ-valerolactones (dihydropyranones) are obtained in fair to good yields by an aldol/aldol/elimination/lactonization domino process that allows the formation of four new bonds in a single step. A putative reaction mechanism is proposed.

The use of a CoBr2/1,10-phenanthroline catalytic system together with Zn as the reductant was developed to prepare diversely substituted indanamines by a Co(I)-catalyzed [3 + 2] annulation of o-haloaryl imines with electron-deficient alkenes in good yields. The use of Mn as the reductant allowed the elaboration of a three-component version of this reaction. These conditions were also found to be suitable for the activation of various halides and were extended to the preparation of the indenamine and strigolactam scaffolds.

The first examples of cobalt-catalyzed multicomponent couplings of mixed aromatic arylzinc reagents with Michael acceptors and carbonyl compounds or imines is described. The reaction system employs a cobalt(II)-2,2′-bipyridine or a cobalt(II)-1,10-phenanthroline complex as a catalyst for both organozinc generation and subsequent multicomponent assembly by formal Michael addition/aldol coupling or Mannich reaction. This study brings new insights into the synthetic scope and mechanism of the reaction.

Galat reactions between aldehydes and substituted malonic acids half oxyester were found to be efficiently catalyzed by morpholine in refluxing toluene. This transformation allows the stereoselective synthesis of diverse α,β-disubstituted acrylates in moderate to good yields. This method constitutes an attractive alternative to existing methods in terms of scope and eco-compatibility.

A century after the pioneering works of Carl Mannich in 1917, the aminoalkylation of carbonylated compounds has become a classical reaction of organic chemistry. Thanks to its modular character, the so-called multicomponent Mannich reaction has found numerous applications throughout the fields of chemistry, especially for synthetic and biomedical purpose. After 100 years of good service, recent developments involving nucleophile diversification through the use of stoichiometric or even catalytic amounts of organometallic species have greatly revitalized this venerable reaction and expanded its scope, thus opening the way to a new world of possibilities. This Microreview on the organometallic Mannich reaction aims to highlight seminal contributions to the field as well as the major progress recently made in this area.

1,2-Disubstituted indolines have been prepared in fair to good yields by a Zn-mediated organometallic Mannich reaction, followed by an intramolecular Pd-catalyzed aromatic amination. The reactions are easy to set up and compatible with a large variety of simple or commercially available reagents. The method was further extended to the preparation of a 1,2,3-trisubstituted indoline.

The intramolecular condensation of β-keto esters to give propargyl alcohols is described. The substrates have two electrophilic sites and two nucleophilic sites. The site selectivity can be fully controlled. In the presence of a calcium-based catalyst and under anhydrous conditions, O-addition products are isolated. On the other hand, traces of water or iPrOH as additive encourage calcium-catalyzed Meyer–Schuster rearrangements. The resulting enones may be further transformed into endo-Michael addition products. The regioselectivity of the attack of the enolate can be changed by using 1-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(dimethylamino)cyclohexyl]thiourea (TUC) as organocatalyst, which promotes the formation of aldol-condensation products of high synthetic interest. DFT calculations rationalize the preference for the aldol condensation when TUC is used instead of the endo-Michael addition.

The reductive Barbier coupling of aromatic halides and electrophiles has been achieved using a CoBr2 /1,10-phenanthroline catalytic system and over stoichiometric amounts of zinc. The reaction displayed a broad scope of substrates, including (hetero)aryl chlorides as pro-nucleophiles and aldehydes or imines as electrophiles, leading to diarylmethanols and diarylmethylamines in moderate to excellent yields, respectively.

The reductive Barbier coupling of aromatic halides and electrophiles has been achieved using a CoBr

International audience; The combination of aminocatalysis with N-heterocyclic carbene catalysis has been extended to a switchable dual catalytic system, which allowed a direct enantioselective entry to bridged bicyclo[3.n.1] ring systems and the total synthesis of the natural product (1R)-suberosanone.

Direct alkenylation of a variety of alcohols with vinylboronic acids has been accomplished using the air-stable calcium(II) complex Ca(NTf2 )2 under mild conditions with short reaction times. For reluctant transformations, an ammonium salt was used as an additive to circumvent the reactivity issue.

International audience; alpha-Oxoketenes generated in situ by a thermal Wolff rearrangement have been found to participate as 1,2-and 1,4-ambident C-electrophilic/O-nucleophilic reagents towards donor/acceptor carbonyl-stabilized Wittig ylides. This resulted in the very direct and practical syntheses of func-tionalized allenes by a normal Wittig olefination, 4H-pyran-4-ones by an abnormal Wittig olefination, or 4H-pyranylidenes following a Wittig/abnormal Wittig cascade sequence as a function of the substrates combination employed. Mechanis-tic experimental and computational studies provided a full rational for these reactivity switches. Some unusual mecha-nistic features for Lewis acid-free Wittig olefinations were identified in this series such as the involvement of betaine intermediates and some degree of reversibility in the normal Wittig olefination. The abnormal Wittig olefination was fully uncovered.

Complexes of type [LAuCl] (L = phosphine, phosphite, NHC and others) are widely employed in homogeneous catalysis, however, they are usually inactive as such and must be used jointly with a halide scavenger. To date, this role has mostly been entrusted to silver salts (AgSbF6 , AgPF6, AgBF4, AgOTf, etc.). However, silver salts can be the source of deactivation processes or side reactions, so it is sometimes advisable to use silver-free cationic gold complexes, which can be difficult to synthesize and to handle compared with the more robust chloride. We show in this study that various Lewis acids of the transition and main group metal families are expedient substitutes to silver salts. We have tested Cu(I), Cu(II), Zn(II), In(III), Si(IV), Bi(III), and other salts in a variety of typical Au(I)-catalyzed transformations, and the results have revealed that [LAuCl] can form active species in their presence.

The cobalt-catalyzed multicomponent reaction between sp2-hybridized organic halides, Michael acceptors and unsaturated electrophiles is described. The reaction proceeds via a formal conjugate addition/aldol or aza-aldol (Mannich) tandem reaction initiated by the in situ metalation of the organic halide by cobalt-catalysis. The essentially new reaction conditions that have been developed are very mild and atom-economic. Under these conditions, a broad range of β-hydroxy- and β-aminocarbonyl compounds are obtained in good to high yields.

The intramolecular condensation of β-keto esters to give propargyl alcohols is described. The substrates have two electrophilic sites and two nucleophilic sites. The site selectivity can be fully controlled. In the presence of a calcium-based catalyst and under anhydrous conditions, O-addition products are isolated. On the other hand, traces of water or iPrOH as additive encourage calcium-catalyzed Meyer–Schuster rearrangements. The resulting enones may be further transformed into endo-Michael addition products. The regioselectivity of the attack of the enolate can be changed by using 1-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(dimethylamino)cyclohexyl]thiourea (TUC) as organocatalyst, which promotes the formation of aldol-condensation products of high synthetic interest. DFT calculations rationalize the preference for the aldol condensation when TUC is used instead of the endo-Michael addition.

A general evaluation of silylated nucleophiles to intercept transient α-oxoketenes generated by microwave-assisted Wolff rearrangement of 2-diazo-1,3-dicarbonyl compounds is presented. Original scaffolds and synthetic intermediates are accessed in a rapid, efficient and easy-to-handle way. Mechanistic studies by DFT calculations and some post-functionalizations are discussed.

International audience; Stereodefined monocyclic, spirobicyclic, and bis-spirotricyclic pyrazolidin-3-ones can be prepared efficiently by a three-component reaction involving a 1,3-dipolar cycloaddition of azomethine imines obtained from hydrazones with alpha-oxo-ketene dipolarophiles generated in situ. The reaction allows the creation of four covalent bonds and two contiguous chiral quaternary centers with excellent diastereoselectivity in a single catalyst/additive-free, highly atom-economical transformation. From a fundamental point of view, the reaction introduces alpha-oxo-ketenes as effective dipolarophiles in 1,3-dipolar cycloadditions.

International audience; Quadranes, discovered with the isolation of (-)-quadrone in 1978, are biologically active naturally occurring sesquiterpenes featuring a distinctive set of bi- to tetracyclic ring systems. The available data for this family of natural products, including isolation data, biosynthetic considerations, a comprehensive compilation of the reported biological activities, and an exhaustive survey of the synthetic work in this area so far, are critically analyzed.

International audience; A general evaluation of silylated nucleophiles to intercept transient α-oxoketenes generated by microwave-assisted Wolff rearrangement of 2-diazo-1,3-dicarbonyl compounds is presented. Original scaffolds and synthetic intermediates are accessed in a rapid, efficient and easy-to-handle way. Mechanistic studies by DFT calculations and some post-functionalizations are discussed.

The first gallium- and calcium-catalyzed Meyer–Schuster rearrangements are described. Under substrate control, the incipient conjugated ketones can be trapped intramolecularly by β-keto esters or amides to yield cyclic products after aldol condensation or endo-Michael addition. An interesting additive effect that promotes the latter tandem process with calcium has been found.

The first gallium- and calcium-catalyzed Meyer–Schuster rearrangements are described. Under substrate control, the incipient conjugated ketones can be trapped intramolecularly by β-keto esters or amides to yield cyclic products after aldol condensation or endo-Michael addition. An interesting additive effect that promotes the latter tandem process with calcium has been found.

Catalytically active species for a variety of transformations are obtained from stable gold complexes using non-silver metal-based activators.

The title reaction allows a simple and mild access to a wide range of unsaturated trifluoromethylated compounds.

Copper-mediated trifluoromethylation of unsaturated organotrifluoroborates with the Langlois reagent (NaSO2CF3) and TBHP allows the introduction of trifluoromethyl groups into a variety of organic substructures. The reactions are easy to set up, the conditions are mild and general, and the process provides access to trifluoromethylated alkynes, alkenes, arenes, and heteroarenes in fair to good yields.

Copper-catalyzed borylation of a variety of organic halides with bis(pinacolato)diboron allows the preparation of diverse potassium organotrifluoroborates. The reactions are mild and general, providing access to a variety of interesting, boron-containing building blocks, including those containing piperidine, pyrrole, azetidine, tetrahydropyran, and oxetane substructures. Representative Minisci reactions are reported for select examples.

The Rh(III)-catalyzed annulations of benzhydroxamates with potassium vinyltrifluoroborate proceed with high regioselectivity in most of the cases and in a fashion that is regiocomplementary to that of most terminal alkenes.