Search

Covering: up to 2015 Iron salts are inexpensive and almost innocuous; they are thus the promoters of choice, even in stoichiometric amounts, for the formation of carbon–carbon bonds in the backbone of complex molecules. This review encompasses the key role of iron complexes in the total synthesis of some natural products or pharmacologically important compounds.

The combination of hexafluoroisopropanol as solvent and high-pressure conditions enables the unprecedented 1,4-addition of poor nucleophiles like aromatic amines onto sluggish Michael acceptors without a promoter or work-up.

The transamidation between formamide and various amines proceeds under heating, without any catalyst nor solvent, providing thus green and neutral conditions for the formylation of primary and secondary amines. The resulting amide product can be directly transformed, in a one pot sequence, into monomethylamine.

The monoalkylation of different primary amines with alkyl triflates proceeds with high chemoselectivity using 1,1,1,3,3,3-hexafluoro-2-propanol as solvent, which prevents an overalkylation.

A direct access for the preparation of fluoroallylamines via an aza-Michael reaction followed by a modified Julia reaction is presented.

A 3-component Povarov reaction between butyraldehyde, aromatic amines and ethyl vinyl ether in trifluoroethanol followed by an oxidation, offers a convenient entry to differently substituted 2-propylquinolines.

The halogen-bonded adduct between DABCO and two molecules of perfluorooctyl iodide efficiently promotes the Morita—Baylis—Hillmann reaction under mild conditions.

The synthesis of 8-aminoquinolines and 1,10-phenanthrolines with substituents in α of the nitrogen has been performed through an inverse-demanding aza-Diels–Alder (Povarov reaction) in the fluoroalcohols TFE or HFIP. This path involves simple starting materials: 1,2-phenylenediamines, enol ethers and aldehydes.

The strong influence of the nature of the leaving group in allylic derivatives in their enantioselective Pd-catalyzed substitution by nucleophile is reported. Analysis of the stereochemical course of the Pd-catalyzed substitution of achiral trans-4-tert-butyl-1-vinylcyclohexyl derivatives with nucleophiles indicates the enantioselective step to be oxidative addition of the allylic substrate onto the chiral Pd complex. The asymmetric induction may be understood as the reuslt of the selection by the chiral Pd catalyst between two reactive enantiomeric conformations of the allylic substrate and, hence, was shown to be strongly dependent upon reaction conditions and especially upon the nature of the substrate leaving group

Commercial sodium tetraphenylborate is a convenient phenylating reagent in the palladium(0)-catalyzed substitution of allylic acetates. Two phenyl groups of NaBPh 4 are available for transfer. Triphenylboron is also a phenylating agent in this reaction.

Base-catalyzed isomerization of achiral (E,E)-1,2,5-triphenylphospholane oxide leads to the racemic (E,Z)-isomer. Resolution of Supercritical Fluid Chromatography (SFC) followed by reduction gives the two enantiomers. The activity of this new ligand is tested in palladium-catalyzed coupling of cyclohex-2-enyl acetate with nucleophiles.

The palladium-catalyzed substitution of carbonates of the titled alcohols was performed at lower temperature than the previously reported reaction of the corresponding acetates. The use of enantiomerically pure carbonates gave substitution products with overall retention of the configuration (up to 97%).

Naphthylmethyl acetates 1a and 2a were substituted by morpholine in DMPU in the presence of 2 mol% of [Pd(dba) 2 + 1.5 dppe] to give products 9–10 in 66–70% isolated yield. In DMF in the presence of benzylamine, N,N-dimethylnaphthylmethylamines 11–12 were produced in 78–85 % isolated yield.

Secondary benzylic alcohols were kinetically resolved by rabbit gastric lipase-mediated acylation with isopropenyl acetate. Among all the substrates tested, a high enantioselectivity was observed only for 1-[2-(6-methoxy)naphthyl]ethanol 3a (E>500). Allylic alcohols 14a and 15a were also efficiently resolved (E = 26 and 51 respectively).

1-Phenylphosphol-2-en-1-oxide 1a reacts with aryl iodides in the presence of ammonium formate and a catalytic amount of Pd(OAc) 2 to give 3-aryl-1-phenylphospholane-1-oxides 3 , whereas 4-aryl-1-phenylphosphol-2-en-1-oxides 4 are obtained from 1-phenylphosphol-3-en-1-oxide 2a under modified Heck reaction conditions (aryldiazonium salt, catalytic Pd(OAc) 2 ).

4-Quinolylmethyl (4-QUI) esters of carboxylic acids and 1-naphthylmethyl (1-NAP) esters of carbonic and carbamic acids are reduced by palladium-catalyzed hydrogenolysis by formate anion. The reaction conditions are compatible with the presence of a benzyl ester and of an alkene double bond.

[reaction: see text] Quinolylmethyl, 1-(isoquinolyl)ethyl, and 1-(quinolyl)ethyl acetates reacted with dimethylmalonate anion in the presence of a Pd(0) catalyst to give products of nucleophilic substitution and/or byproducts, depending upon the substitution pattern. The observed side reactions were reduction in the case of primary acetates and elimination or elimination/Michael-type addition sequence for secondary substrates.

Palladium-catalyzed cross-coupling reaction of β-amino and β-ethoxy-β-trifluoromethyl vinyl bromides with terminal alkynes and terminal olefins has been achieved to afford new CF3-substituted 1,3-enynes and 1,3-dienes, which can undergo carbolithiation.

Acetylquinolines and acetylisoquinolines were obtained from the corresponding chloro-, bromo- or trifluoromethylsulfonyloxy-heteroaromatics via four different palladium-catalyzed coupling reactions: (i) Stille coupling with tri(n-butyl)-1-ethoxyvinylstannane; (ii) Negishi coupling with 1-ethoxyvinylzinc chloride; (iii) cross-coupling with tri(1-ethoxyvinyl)indium; (iv) Heck arylation of n-butyl vinyl ether.

The fluoroalkylketone 2 is an efficient catalyst in the epoxidation reaction using Oxone® as oxidant. In hexafluoro-2-isopropanol (HFIP), the ketone can be used in a catalytic amount (1 or 5 mol%) with only 1.5 equiv. of Oxone®. The reaction gave good yields of epoxides for a number of olefin substrates, included low reactive ones.

1,4-Addition of anilines onto Michael acceptors proceeds easily in specific polar protic solvents, without any promoting agent. According to the solvent and to the electrophile, the selectivity of the reaction can be finely tuned. With methyl acrylate as electrophile, only monoaddition takes place in water, while the diadduct is yielded in hexafluoroisopropyl alcohol (HFIP). The use of methyl vinyl ketone as a partner affords the monoadduct in water, the diadduct in trifluoroethanol (TFE), and the quinoline in HFIP.

The synthesis of pyrazoles via1,3-dipolar cycloaddition of diazo compounds to alkynes proceeds easily by heating. With α-diazocarbonyl substrates the reactions are conducted under solvent-free conditions affording the pyrazole products in high yields without any work up or purification.

Hexafluoroisopropanol (HFIP) is explored as an effective medium for the synthesis of 2,3-unsaturated glycosides through allylic rearrangement of 3,4,6-tri-O-acetyl glucal. This metal-free, exclusively solvent-promoted Ferrier glycosylation, affords products in good to excellent yields and with good α-selectivity.

A short and facile preparation of analogues of DMAP (F-DMAPs) labelled with fluorous chains is reported. These catalysts efficiently promote the acylation of alcohols with anhydrides (Ac2O, (i-PrCO)2O) and can be partially recovered and reused. The effectiveness of F-DMAP is similar to that of DMAP.

gem -Chloroamine CF 3 CH(Cl)NHAc 1 reacts in a one-pot sequence with NaN 3 to afford trifluoromethyl azido compound 2 and further undergoes a Huisgen 1,3-dipolar cycloaddition with alkynes to yield 1,4-disubstitued 1,2,3-triazoles. The reaction is catalyzed by Cu(II) species (Cu(OAc) 2 , 10 mol %) without any reducing agent, and the corresponding products are afforded in high yields (74–87%). This process offers thus an entry to new trifluoromethyl pseudopeptides.

The development of an enantioselective sulfide oxidation involving a chiral iron catalyst and aqueous hydrogen peroxide as oxidant is described. In the presence of a simple carboxylic acid, or a carboxylate salt, the reaction affords sulfoxides with remarkable enantioselectivities (up to 96 % ee) in moderate to good yields. The influence of the structure of the additive on the reaction outcome is reported. In the sulfoxide-to-sulfone oxidation a kinetic resolution (with s = 4.8) occurs, which, however, plays only a negligible role in the overall enantioselective process. Furthermore, a positive nonlinear relationship between the ee of the product and that of the catalyst has been found. On the basis of these observations, a possible catalyst structure is proposed.

Trifluoromethylated nitrogen-containing molecules have been shown to have important biological effects and their synthesis is in the focus of the pharmaceutical industry. In the last few years, simple nitrogen derivatives of fluoral, i.e. imines, acetals and oxazolidines, have emerged as powerful building blocks to synthesize these target molecules and relevant precursors. This review summarizes the chemistry of these "N-derivatives of fluoral", with special highlight on the syntheses of peptidomimetic units (amino alcohols, amino acids...) and heterocycles (piperidines, beta-lactams...).

A straightforward route to trifluoromethyl analogs of piperidines is described. These syntheses involve a Barbier-type allylation reaction of trifluoroacetaldimines, followed by N-allylation (one-pot), and ring-closing metathesis. An efficient asymmetric version is also reported (>98 % de). Functionalized heterobicyclic compounds can also be obtained by a Pauson–Khand reaction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

An iron-catalyzed asymmetric sulfide oxidation is the key step in the synthesis of the non-steroidal anti-inflammatory drug Sulindac. Both enantiomers of the chiral product can be prepared with 92% ee in good yield.

A new iron(III) halide-promoted aza-Prins cyclization between γ,δ-unsaturated tosylamines and aldehydes provides six-membered azacycles in good to excellent yields. The process is based on the consecutive generation of γ-unsaturated-iminium ion and further nucleophilic attack by the unsaturated carbon−carbon bond. Homoallyl tosylamine leads to trans-2-alkyl-4-halo-1-tosylpiperidine as the major isomer. In addition, the alkyne aza-Prins cyclization between homopropargyl tosylamine and aldehydes gives 2-alkyl-4-halo-1-tosyl-1,2,5,6-tetrahydropyridines as the only cyclic products. The piperidine ring is widely distributed throughout Nature, e.g., in alkaloids,1 and is an important scaffold for drug discovery, being the core of many pharmaceutically significant compounds.2,3 The syntheses of these type of compounds have been extensively studied in the development of new drugs containing six-membered-ring heterocycles.4 Reactions between N-acyliminium ions and nucleophiles, also described as amidoalkylation or Mannich-type condensations, have been frequently used to introduce substituents at the R-carbon of an amine.5 There are several examples that involve an intramolecular attack of a nucleophilic olefin into an iminium cation for the construction of a heterocyclic ring system.6 Traditionally, the use of hemiaminals or their derivatives as precursors of N-acyliminium intermediates has been a common two-step strategy in these reactions.6a Among this type of cyclization is the aza-Prins cyclization,7 which uses alkenes as intramolecular nucleophile. However, cy† X-ray analysis. E-mail address: malopez@ull.es. (1) (a) Fodor, G. B.; Colasanti, B. Alkaloids: Chemical and Biological PerspectiVes; Pelletier, S. W., Ed.; Wiley: New York, 1985; Vol. 23, pp 1-90. (b) Baliah, V.; Jeyarama, R.; Chandrasekaran, L. Chem. ReV. 1983, 83, 379-423. (2) Watson, P. S.; Jiang, B.; Scott, B. Org. Lett. 2000, 2, 3679-3681. (3) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. ReV. 2003, 103, 893-930. (4) Buffat, M. G. P. Tetrahedron 2004, 60, 1701-1729 and references therein. (5) Speckamp, W. N.; Moolenaar, M. J. Tetrahedron 2000, 56, 3187- 3856 and references therein. (6) (a) Hiemstra, H.; Speckamp, W. N. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, O., Heathcock, C. H., Eds.; Pergamon: New York, 1991; Vol. 2, pp 1047-1081. (b) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41, 4367-4416. (7) (a) Dobbs, A. P.; Guesne, S. J. J.; Hursthouse, M. B.; Coles, S. J. Synlett 2003, 11, 1740-1742. (b) Dobbs, A. P.; Guesne, S. J. J.; Martinove, S.; Coles, S. J.; Hursthouse, M. B. J. Org. Chem. 2003, 68, 7880-7883. (c) Hanessian, S.; Tremblay, M.; Petersen, F. W. J. Am. Chem. Soc. 2004, 126, 6064-6071 and references therein. (d) Dobbs, A. P.; Guesne, S. J. Synlett 2005, 13, 2101-2103. ORGANIC