Josefa Flórez

Carbon nucleophile addition to sp2-unsaturated Fischer carbene complexes

Abstract The reactions of group 6 (alkoxy)(aryl)- and (alkoxy)(alkenyl)carbene complexes with organolithium compounds, metal enolates, and enamines are summarized. (Alkoxy)(aryl)carbene complexes underwent mainly nucleophilic addition to the carbene carbon atom, but either 1,4- or 1,6-addition products have been observed with derivatives bearing a bulky alkoxy group and phenyl- or alkyllithiums. The more widely studied (alkoxy)(alkenyl)carbene complexes react with carbon nucleophiles to give 1,2- or 1,4-addition products depending on the steric surroundings of both the metal carbene complex and the nucleophile as well as the nature of the latter. These reactions have been employed for several useful carbon-carbon bond-forming processes taking place with high diastereoselectivity.

β-substituted organolithium compounds from chlorohydrins: application to the direct synthesis of bifunctionalized organic compounds

The reaction of different chlorohydrins with n-butyl-lithium at –78 °C followed by metallation with lithium naphthalenide at the same temperature leads to very reactive organolithium compounds bearing an alkoxide function at the β-position with respect to the metal. The reaction of these intermediates with several electrophiles leads to mono- as well as bi-functionalized organic compounds. Thus, treatment of these dianions with deuterium oxide, oxygen, carbon dioxide, benzyl bromide, dimethyl disulphide, and carbonyl compounds, gave 2-deuterioalcohols, 1,2-diols, β-hydroxy-acids, 2-benzyl alcohols, 2-hydroxy-thioethers, and 1,3-diols respectively. The preparation of β-substituted organolithium derivatives can be alternatively carried out starting from α-chloroketones by the same procedure. When the lithium atom is linked to a secondary carbon atom the dianions are very unstable and decompose, even at –100 °C, by β-elimination yielding the corresponding olefins.

Diastereoselective cyclopropanation of ketone enols with Fischer carbene complexes.

Treatment of aryl/heteroaryl methoxycarbene complexes of chromium with -substituted ketone lithium enolates between -78 degrees C and room temperature resulted in the diastereoselective synthesis of 1,2,2,3-tetrasubstituted cyclopropanols. An exception has been observed in the reaction with cyclohexanone lithium enolate that yielded a bicyclic 2-buten-4-olide. 1,2-Dimethoxycyclopropanes and 1-methoxy-2-trimethylsilyloxycyclopropanes were isolated by quenching the reactions with MeOTf or Me3SiCl, respectively. This novel cyclopropanation process involves formation of lithium (3-oxoalkyl)pentacarbonylchromate intermediates which on warming undergo intramolecular addition to the carbonyl group. This cyclization is equivalent to the cyclopropanation in smooth conditions of electron-rich alkenes with Fischer carbene complexes.

β-Substituted organolithium compounds; direct preparation and reactivity

Very reactive organolithium compounds bearing an alkoxide function at the β-position with respect to the metal are obtained by direct metallation with lithium naphthalenide at low temperature of the corresponding lithium chlorhydrin salt; the reaction of these dianions with different electrophilic agents leads to the corresponding mono- and bi-functionalized compounds.

Enantioselective Multicomponent Synthesis of Fused 6–5 Bicyclic 2‐Butenolides by a Cascade Heterobicyclisation Process

The successive coupling of an alkoxy(aryl/heteroaryl)carbene complex of chromium with either a ketone or an imide lithium enolate and then a 3-substituted (H, TMS, PhCH(2), PhCH(2)CH(2), Me) propargylic organomagnesium reagent has afforded novel hydroxy-substituted bicyclic [4.3.0]-γ-alkylidene-2-butenolides with three modular points that has allowed the efficient introduction of molecular complexity, including a homopropargylic alcohol core. The selective formation of these five- or six-component heterobicyclisation products is the result of the regioselective integration of the Grignard reagent as a propargyl fragment followed by a cascade CO/alkyne/CO insertion, ketene trapping and elimination sequence. By using lithium enolates of chiral N-acetyl-2-oxazolidinones and the corresponding propargylic organocerium reagents, both enantiomers of these bicyclic heterocycles were efficiently prepared with very high enantiomeric purity. Architecturally, these fused bicyclic butenolides are characterised by a highly unsaturated and oxygenated core and they exhibit strong blue fluorescence in solution.

Tricyclic ethers from fischer vinylcarbene complexes and β-oxygen-functionalized organolithium compounds

A one-pot synthesis of tricyclic ring systems has been achieved by the Michael addition of β-oxygen-functionalized organolithium compounds to Fischer vinylcarbene complexes followed by an intramolecular alkoxide exchange and intramolecular cyclopropanation reaction.

Direct coupling between β-functionalized organolithium compounds and aryl and vinyl halides

Abstract Treatment of N-lithio-N-(2-lithioethyl)benzamide with different aromatic and vinylic halides affords directly the corresponding substitution products: functionalized benzamides 3 – 10.

2‐ and 3‐Haloalkoxy Fischer Carbene Complexes of Chromium as Synthons for either Hydroxycyclopropanation or Oxaspirocyclopropanation of Alkenes

The thermal reaction of 2-haloethoxy- and 3-chloropropoxy(alkenyl)carbene complexes of chromium with electronically neutral alkenes furnished diastereoselectively the corresponding 1-haloalkoxy-l-vinylcyclopropanes that, subjected to subsequent halogen-lithium exchange reactions, provided vinylcyclopropanols or compounds containing the spiro[cyclopropane-tetrahydrofuran/tetrahydropyran] structure, depending on the nature of both the halogen atom and the lithiating reagent. The hydroxycyclopropanation reaction can be efficiently achieved in a one-pot fashion.

Mononuclear Biscarbene Complexes by Direct Nucleophile Addition to a CO Ligand of Fischer Arylcarbene Complexes

Mononuclear Group 6 Fischer biscarbene complexes I, which are organometallic compounds that have two carbene ligands bonded to the same transition-metal atom, have been much less investigated than the corresponding Fischer monocarbene complexes II (Figure 1). Only very few examples of this class of compounds I have been reported and characterized by reactivity and/or X-ray studies, and their synthetic potential remains to be explored. In addition, there is a lack of a general method to produce such complexes.

Water Freezing as a Regiocontrol Element in the Multicomponent Assembly of Cyclic Enones

Regioselective synthesis of dialkoxy 2-cyclopentenones and 2-cyclohexenones with novel substitution patterns has been accomplished by the one-pot combination of three simple starting materials (chromium carbene complex, Weinreb acetamide lithium enolate and 1-alkoxyallenyllithium) under either anhydrous conditions or water-promoted solidification of the reaction mixture. These results revealed an unprecedented water-freezing effect that plays a key role to completely reverse the regioselectivity of the intramolecular carbometalation of an allene moiety.