Francesco Fini

Organocatalytic Asymmetric Diels-Alder Reactions of 3-Vinylindoles

Diels–Alder type reactions are amongst the most useful transformations in organic chemistry for the construction of cyclohexene structures, often containing multiple stereocenters. Catalytic asymmetric variants of these [4+2] cycloadditions have been reported for different diene–dienophile combinations, showing in several instances outstanding synthetic utility. Herein, we present the development of an unprecedented catalytic asymmetric Diels–Alder reaction of 3-vinylindoles 1 with different representative dienophiles 2 (Scheme 1). Our studies were motivated by the stunning

Organocatalytic Asymmetric Formal [3 + 2] Cycloaddition with in Situ-Generated N-Carbamoyl Nitrones

A novel organocatalytic formal [3 + 2] cycloaddition reaction with in situ generation of N-carbamoyl nitrones is presented. For the first time, N-Boc- and N-Cbz-protected isoxazolidines have been directly obtained as single diastereoisomers in generally high yields and enantiomeric excesses using mild reaction conditions and inexpensive, readily available Cinchona alkaloid quaternary ammonium salts as catalysts. Synthetic manipulations of the products provided highly valuable building blocks such as free isoxazolidines, a N-Boc-1,3-aminoalcohol, and a free delta-lactam. This report represents a pioneering work in the use of N-carbamoyl nitrones as electron-poor 1,3-dipoles and glutaconates as new dipolarophiles in asymmetric catalysis.

Catalytic asymmetric Mannich reactions of sulfonylacetates.

Aryl and heteroaryl sulfones are very versatile intermediates in organic chemistry. Owing to their strong electron-withdrawing properties, sulfonyl moieties are able to stabilize a carbanion at the a position, as well as to activate a conjugated double bond for nucleophilic addition. After conferring the desired reactivity, the sulfonyl moiety can be removed by reduction or transformed into another useful functionality, such as a C C double bond or a ketone, through simple synthetic manipulations. For these reasons, the development of catalytic asymmetric transformations that lead to enantiomerically enriched sulfonyl compounds has received much attention. In particular, vinyl sulfones have been used as electron-deficient olefins, and a-substituted sulfones have been used for the generation of various nucleophilic species or carbenes. In contrast, the employment of arylsulfonylacetates 1 in a catalytic asymmetric setting has to our knowledge never been reported, although these readily enolizable compounds could conceivably be used as convenient synthetic equivalents of a anions of carboxylic acid derivatives (Scheme 1). We considered the possibility of using phase-transfer catalysis (PTC) for the mild deprotonation of arylsulfonylacetates 1 with the aim of exploring their enantioselective Mannich addition to highly reactive N-carbamoyl imines generated in situ from a-amidosulfones 2 (Scheme 1). The use of PTC with a-amidosulfones 2 as imine surrogates should guarantee broad substrate scope, user-friendly conditions, as well as useful N-carbamoyl protecting groups (Pg) on the nitrogen atom which would further enhance the versatility of the approach.. Our efforts were motivated by the various possible transformations of the Mannich adducts 3. For example, the reductive removal of the sulfonyl moiety would lead to N-protected b-amino acid esters 4 in one step, whereas an oxidative desulfonylation would give a-ketob-aminoesters 5 (Scheme 1). Optically active a-alkylidene b-aminoesters 6, generally referred to as aza-Morita–Baylis– Hillman (aza-MBH) adducts, could instead be accessed through a Julia-type olefination process. Owing to their various applications and biological properties, the preparation of b-amino acid derivatives of type 4–6 in enantiomerically enriched form has been the focus of tremendous effort in the last few years; remarkably, organocatalytic Mannich reactions with acetate donors equipped with removable activating groups are amongst the most attractive approaches reported to date. At the outset of our studies on the reaction between arylsulfonylacetates 1 and a-amidosulfones 2 under PTC conditions, we invariably observed the formation of a nearly equimolar mixture of two diastereoisomers 3 with almost identical ee values. This observation was accounted for in terms of an epimerization of the stereogenic center bonded to the sulfonyl group in adducts 3 under the basic reaction conditions. As this stereogenic center is lost in the final products 4–6, the real goal of our catalytic transformation, we proceeded to optimize the reaction conditions and catalyst structure (Table 1). Commercially available methyl phenylsulfonylacetate (1a) was chosen as the Mannich donor for some preliminary experiments, which showed that it was possible to carry out the catalytic transformation with moderate enantioselectivity in toluene at 30 8C with aqueous K3PO4 (50 % w/w) as the base and a quaternary ammonium salt derived from inexpensive quinidine as the catalyst. We screened catalysts 7a–e (Table 1, entries 1–5), all of which contain ortho substituents in the benzylic moiety attached to the quinuclidine N atom, and found that the 2,6-difluoro derivative 7 e was the most efficient in terms of enantioinduction in the reaction with a-amidosulfone 2a Scheme 1. Catalytic asymmetric Mannich reaction of sulfonylacetates. Pg = tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz).

Catalytic Enantioselective Addition of Sodium Bisulfite to Chalcones

Dr. F. Fini, M. Scagnetti, Prof. M. F. A. AdamoCentre for Synthesis and Chemical Biology (CSCB)Department of Pharmaceutical and Medicinal ChemistryRoyal College of Surgeons in Ireland123 St. Stephen’s Green, Dublin 2 (Ireland)Fax: ( +353)1-402-2168E-mail: madamo@rcsi.ieHomepage: https://research1.rcsi.ie/pi/madamo/[

Catalytic Oxidative Carbonylation of Amino Moieties to Ureas, Oxamides, 2-Oxazolidinones, and Benzoxazolones

The direct syntheses of ureas, oxamides, 2-oxazolidinones, and benzoxazolones by the oxidative carbonylation of amines, β-amino alcohols, and 2-aminophenols allows us to obtain high value added molecules, which have a large number of important applications in several fields, from very simple building blocks. We have found that it is possible to perform these transformations using the PdI2 /KI catalytic system in an ionic liquid, such as 1-butyl-3-methylimidazolium tetrafluoroborate, as the solvent, the solvent/catalyst system can be recycled several times with only a slight loss of activity, and the product can be recovered easily by crystallization.

Analogies and Differences in Palladium‐Catalyzed CO/Styrene and Ethylene/Methyl Acrylate Copolymerization Reactions

The catalytic CO/styrene and ethylene/methyl acrylate copolymerizations are compared for the first time by applying the same precatalysts. With this aim, PdII neutral, [Pd(CH3)Cl(N–N)], and monocationic, [Pd(CH3)(L)(N–N)][PF6] (L=CH3CN, DMSO), complexes with 1‐naphthyl‐ and 2‐naphthyl‐substitued α‐diimines with both an acenaphthene and a diazabutadiene skeleton as chelating nitrogen‐donor ligands (N–N) have been studied. In the case of the complexes with the 1‐naphthyl‐substituted ligands, syn and anti isomers are found both in solid state and in solution. All the monocationic complexes generate active catalysts for the CO/styrene copolymerization leading to atactic or isotactic/atactic stereoblock copolymers depending on the ligand bonded to palladium. Instead, in the case of the ethylene/methyl acrylate copolymerization only the complexes with the 1‐naphthyl‐substituted ligands generate catalysts for this reaction.

Palladium(II)-Catalyzed Cross-Dehydrogenative Coupling (CDC) of N-Phthaloyl Dehydroalanine Esters with Simple Arenes: Stereoselective Synthesis of Z-Dehydrophenylalanine Derivatives

Pd(II)-catalyzed cross-dehydrogenative coupling (CDC) of methyl N-phthaloyl dehydroalanine esters with simple aromatic hydrocarbons is reported. The reaction, which involves the cleavage of two sp(2) C-H bonds followed by C-C bond formation, stereoselectively generates highly valuable Z-dehydrophenylalanine skeletons in a practical, versatile, and atom economical manner. In addition, a perfluorinated product was expediently converted into important nonproteinogenic amino acid building blocks through copper-catalyzed conjugate additions of boron, silicon, and hydride moieties.