Mechanistic Facets of the Competition between Cross-Coupling and Homocoupling in Supporting Ligand-Free Iron-Mediated Aryl-Aryl Bond Formations.

In the context of cross-coupling chemistry, the competition between the cross-coupling path itself and the oxidative homocoupling of the nucleophile is a classic issue. In that case, the electrophilic partner acts as a sacrificial oxidant. We investigate in this report the factors governing the cross- versus homocoupling distribution using aryl nucleophiles ArMgBr and (hetero)aryl electrophiles Ar'Cl in the presence of an iron catalyst. When electron-deficient electrophiles are used, a key transient heteroleptic [Ar2Ar'FeII]- complex is formed. DFT calculations show that an asynchronous two-electron reductive elimination follows, which governs the selective evolution of the system toward either a cross- or homocoupling product. Proficiency of the cross-coupling reductive elimination strongly depends on both π-accepting and σ-donating effects of the FeII-ligated Ar' ring. The reactivity trends discussed in this article rely on two-electron elementary steps, which are in contrast with the usually described tendencies in iron-mediated oxidative homocouplings which involve single-electron transfers. The results are probed by paramagnetic 1H NMR spectroscopy, experimental kinetics data, and DFT calculations.

Gram-Scale, Cheap, and Eco-Friendly Iron-Catalyzed Cross-Coupling between Alkyl Grignard Reagents and Alkenyl or Aryl Halides.

A new robust methodology for gram-scale iron-catalyzed cross-coupling between alkyl Grignard reagents and alkenyl or aryl halides is developed. This method does not require toxic additives such as NMP or expensive ligands. Its efficiency relies on the use of simple alkoxide magnesium salts as additives. On the basis of these results, a new procedure for one-pot synthesis of substituted benzamides from chloroesters is also proposed.

Stereoselective synthesis of triarylethylenes via copper-palladium catalyzed decarboxylative cross-coupling: synthesis of (Z)-tamoxifen.

The first Cu/Pd-catalyzed decarboxylative cross-coupling of 3,3-diarylacrylic acids with aryl bromides is described. Triarylethylenes were obtained in high yields with excellent stereoselectivities. This methodology was successfully applied to the stereoselective synthesis of (Z)-tamoxifen.

Iron thiolate complexes: efficient catalysts for coupling alkenyl halides with alkyl Grignard reagents.

Ironing out the kinks: Efficient new catalytic systems based on iron thiolates are described for the iron-catalyzed cross-coupling of alkyl Grignard reagents with alkenyl halides. The reaction is highly chemo- and stereoselective. With this new procedure, the use of N-methylpyrrolidone as a co-solvent is no longer required.

Iron-catalyzed oxidative heterocoupling between aliphatic and aromatic organozinc reagents: a novel pathway for functionalized aryl-alkyl cross-coupling reactions.

Aryl-alkyl cross-coupling products are obtained by the iron-catalyzed oxidative heterocoupling of organozinc reagents under mild conditions. This novel reaction pathway is versatile, allowing for the use of primary and secondary aliphatic diorganozinc reagents as coupling partners as well as tolerating functionalized aryl- and alkylzinc reagents.

A new efficient catalytic system for the chemoselective cobalt-catalyzed cross-coupling of aryl Grignard reagents with primary and secondary alkyl bromides.

The cobalt-catalyzed alkylation of aromatic Grignard reagents is performed in good yields by using a new simple and efficient catalytic system: CoCl(2)/TMEDA (1:1). Primary and secondary cyclic or acyclic alkyl bromides were used successfully. The reaction is highly chemoselective since ester, amide, and keto groups are tolerated. The procedure is inexpensive and very easy to carry out on a larger scale.

Manganese-catalyzed cross-coupling reaction between aryl Grignard reagents and alkenyl halides.

Aryl Grignard reagents react stereospecifically with alkenyl halides in the presence of manganese chloride (10%) to afford good yields of cross-coupling products.

Stereoselective preparation of dienol phosphates from alpha,beta-ethylenic aldehydes.

The first stereoselective method of preparation of (E)-dienol phosphates from alpha,beta-ethylenic aldehydes is described. The key point is the stereoselective enolization of conjugated alkenals by potassium tert-butoxide in the presence of N-methylpyrrolidinone (NMP).

Efficient preparation of terminal conjugated dienes by coupling of dienol phosphates with grignard reagents under iron catalysis.

An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the presence of Fe(acac)3 is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone of Diparopsis castanea according to a very expeditious strategy.

Iron-catalyzed alkylation of alkenyl Grignard reagents.

The first iron-catalyzed cross-coupling reaction between alkenyl Grignard reagents and n- or s-alkyl bromides is described. The reaction is stereoselective and takes place in the presence of 5 mol % of [Fe(acac)3/TMEDA/HMTA] (1:2:1) under very mild conditions (THF, 0 degrees C, 45 min).

Iron-catalyzed homo-coupling of simple and functionalized arylmagnesium reagents.

Iron-catalyzed homo-coupling of simple and functionalized arylmagnesium reagents is described. The reaction is highly chemoselective (CN, COOEt and NO(2) groups are tolerated). The procedure was used to perform intramolecular couplings. This cyclization reaction is the key step of the total synthesis of the N-methylcrinasiadine.

Unexpected cross-coupling reaction between o-chloroaryl ketones and organomanganese reagents.

Alkyl- and arylmanganese reagents react with o-chloro or o-bromoaryl ketones to give the substituted ketones in high yields. The cross-coupling reaction is performed under mild conditions (-60 to +40 degrees C, 30 min to 4 h) and takes place with excellent chemoselectivity. [reaction: see text]

Synthesis of alpha-hydrazino ketones via regio- and stereoselective electrophilic amination of manganese enolates and enamines.

A straightforward procedure for the regio- and stereoselective synthesis of alpha-hydrazino ketones is described. Manganese enolates and manganese enamines derived from ketones and from the corresponding N-sulfinylimines react with azodicarboxylate esters (DTBAD and DEAD) in a regioselective fashion to afford in good to excellent yields the kinetic alpha-hydrazino ketones as sole or highly prevalent products. When enantiopure N-sulfinyl manganese enamines were used the stereoselectivity of these reactions ranged from 40% to 68% ee.