Aldo Caiazzo

An original approach to 5,6-dihydroindolizines from 1-allylpyrroles by a tandem hydroformylation/cyclization/dehydration sequence

Abstract 6-Methyl-5,6-dihydroindolizine and 3- or 2-ethyl derivatives were obtained via a one-pot hydroformylation/cyclization/dehydration sequence starting from 1-(2-methyl-2-propenyl)pyrroles. 7-Phenyl-5,6-dihydroindolizine and 5-methyl-5,6-dihydroindolizine were similarly synthesized. An easily occurring electrophilic aromatic substitution by the carbon atom of the carbonyl group on the α-position of the pyrrole ring with the formation of the six-membered ring is the key-step of the process.

Rhodium-catalyzed hydroformylation of 1-allylpyrrole as an unexpected way to 5,6-dihydroindolizine synthesis

Abstract When 1-allylpyrrole was subjected to hydroformylation conditions with Rh 4 (CO) 12 as the catalyst precursor, at 120 atm total pressure, at 20 and 100°C, 5,6-dihydroindolizine was found unexpectedly, together with the expected branched aldehyde, the linear isomer being obtained in traces amounts only. An annulation via a nucleophilic attack of the pyrrole C2 carbon atom on the carbonyl group of the linear aldehyde, followed by dehydration of the intermediate alcohol, possibly generates the indolizine structure.

Rhodium-catalyzed hydroformylation of vinylidenic olefins: the different behaviors of the isomeric alkyl–metal intermediates as the origin of the β-regioselectivity

The β-regioselective hydroformylation of the vinylidenic olefins 2-phenylpropene (1a), 2-methylpropene (1b) and 2,3,3-trimethylbutene (1c) was investigated via deuterioformylation experiments [100°C, 100 atm, Rh4(CO)12] carried out at partial substrate conversion. The crude reaction mixtures were directly submitted to 2H NMR analyses. The results obtained allowed to conclude that whereas the primary rhodium–alkyl intermediate undergoes migratory insertion on CO, giving the corresponding linear aldehyde, the tertiary rhodium–alkyl intermediate, when it does form (i.e., in the case of 1a and 1b but not in the case of 1c), undergoes β-hydride elimination exclusively, accounting for the almost complete β-regioselectivity.

High α-regioselectivity in the rhodium-catalyzed hydroformylation of vinylpyrroles

Abstract The Rh 4 (CO) 12 -catalyzed hydroformylation at low temperature (40°C) of the 1-, 2- and 3-vinylpyrrole gives the corresponding branched aldehydes 2-(1-pyrrolyl)propanal, 2-(2-pyrollyl)propanal and 2-(3-pyrrolyl)propanal with high α-regioselectivity.

Chemoselectivity in the rhodium-catalyzed hydroformylation of 4-vinylpyridine: crucial role of phosphine ligand in promoting carbonylation instead of hydrogenation

Abstract Hydroformylation of 4-vinylpyridine (4VP) in benzene with Rh4(CO)12/PMe2Ph or Rh4CO12 as catalytic precursor shows completely different chemoselectivity, carbonylation product (branched aldehyde) largely prevailing with the first catalyst, hydrogenation product 4-ethylpyridine (4EP) with the second one. Different phosphines and P/Rh ratios were also used, and a comparison with 3-vinylpyridine (3VP) under the same experimental conditions was made too. In all the experiments 3VP exclusively gives aldehidic products. In the case of 4VP, hydrogenation prevails on carbonylation at low P/Rh ratio (

New methods for the synthesis of heterocyclic compounds

Due to frequent occurrence of nitrogen-containing groups among the biologically active compounds, chemoselective functionalization of organic molecules with nitrogen-containing functional groups is an important area of organic synthesis. We have proposed and implemented a new strategy toward design of nitrogen-transfer reactions on inert electrode surfaces with a particular focus on the generation and trapping of highly reactive nitrogen-transfer agents. A wide range of structurally dissimilar olefins can be readily transformed into the corresponding aziridines. The resulting aziridines are precursors to a range of catalysts via nucleophilic ring-opening with diaryl- and dialkyl phosphines. Another strategy explored in the context of oxidative nitrogen transfer is cycloamination of olefins using NH aziridines.

A shortcut hydroformylation route to 7-formyl-5,6-dihydroindolizine from 1-allyl-2-formylpyrrole

When 1-allyl-2-formylpyrrole (1) was subject to hydroformylation conditions with Rh4(CO)12 as catalyst precursor, at 100 atm total pressure and 100°C, 7-formyl-5,6-dihydroindolizine (2′) was produced together with the expected branched aldehyde (3), the linear isomer (2) being obtained in traces only. An intramolecular aldol condensation between the carbon atom adjacent to the formyl group in the chain and the carbonyl group directly bonded to pyrrole ring most likely generates the indolizine structure.

Stepwise hydroformylation of C,N-divinylpyrroles with Rh4(CO)12 under mild conditions: an original synthesis of N-vinylpyrrolylmonoaldehydes and of pyrrolyldialdehydes

1,3-Divinylpyrrole and 1,2-divinylpyrrole were treated in a stainless steel autoclave with Rh4(CO)12 at 40°C and 120 atm of H2/CO total pressure: for both substrates exclusive hydroformylation of the vinyl groups bonded to the ring carbon atom occurred, the branched unsaturated monoaldehydes 2-(1-vinylpyrrolyl)propanals being formed with a very high chemoselectivity and α-regioselectivity. At 80°C only 1,3-divinylpyrrole gives, via hydroformylation of N-vinyl group, the corresponding dialdehydes.

Rhodium-Catalyzed Hydroformylation of 2-Vinyl- and 3-Vinyl-1-tosylpyrroles As a Convenient Synthetic Route to the Corresponding 2-(1-Tosylpyrrolyl)propanals and Derivatives

Abstract: 2-(1-Tosylpyrrolyl)propanals 2a-b were conveniently prepared (70% yield) via rhodium-catalyzed hydroformylation of the corresponding 2-vinyl- and 3-vinyl-1-tosylpyrroles 1a-b and successfully transformed into some new derivatives (50–90% yield).