Diego J. Ramón

Transition-metal-free O-, S-, and N-arylation of alcohols, thiols, amides, amines, and related heterocycles.

A new protocol for the Ullmann-type arylation process of different aromatic heterocycles without any transition-metal catalyst, implying the use of a combination of an excess of potassium hydroxide and dimethyl sulfoxide, is described. The reaction can be performed between a broad range of starting nucleophiles including phenol, alcohols, amines, nitrogen-containing five-membered systems such as pyrazoles, imidazoles, and indoles, and amides with haloarenes, iodide and bromide derivatives giving the best results, the possible pathway involving the in situ generation of the corresponding benzyne intermediate. When the reaction was performed with 2-iodoaniline and either carboxamides or isothiocyanato derivatives, the corresponding benzoazole derivatives were obtained.

New Methodologies Based on Arene-Catalyzed Lithiation Reactions and Their Application to Synthetic Organic Chemistry

The applications of arene-catalyzed lithiation reactions during recent years are reviewed. This methodology has been used to obtain functionalized organolithium compounds from halogenated as well as nonhalogenated materials, such as heterocycles, sulfones, triflates, ethers, thioethers, amides, and esters. This arene-catalyzed lithiation has also been used in the preparation of polylithiated intermediates. Sub-stoichiometric amounts of the arene may be supported on a polymeric material, its catalytic activity being as efficient as in the solution version.

Transition-Metal-Free Indirect Friedländer Synthesis of Quinolines from Alcohols†

The synthesis of polysubstituted quinolines can be easily and greenly accomplished by the direct reaction between the corresponding 2-aminobenzylic alcohol derivative and either a ketone or alcohol in the presence of a base, without any transition-metal catalyst.

Highly enantioselective arylation of ketones

Abstract The enantioselective arylation of different ketones was successfully performed using several arylzinc reagents, titanium tetraisopropoxide and substoichiometric amounts of trans -1,2-bis(hydroxycamphorsulfonylamino)cyclohexane as chiral C 2 -symmetric ligand, the enantiomeric excess reaching up to 96%.

Synthesis of new C2-symmetrical bis(hydroxycamphorsulfonamide) ligands and their application in the enantioselective addition of dialkylzinc reagents to aldehydes and ketones

Abstract The preparation of several C 2 -symmetric disulfonamides derived from chiral camphorsulfonyl chloride and different diamines (with or without stereogenic elements) is described. Their use in the titanium tetraisopropoxide-promoted enantioselective addition of dialkylzinc reagents to aldehydes has been tested, the best enantiomeric excess being up to 76%. Moreover, the unusual addition of dialkylzinc reagents to ketones can also be achieved with excellent enantioselectivity (up to 92% e.e.) using this type of ligand. When using para -substituted phenones as electrophiles, the enantiomeric excess of the resulting tert -alcohol is independent of the electronic properties of the group attached to the aromatic ring of the phenone. In the case of using more hindered ketones the enantioselectivity is lower, so indicating a steric influence in the reaction.

Naphthalene-catalysed lithiation of 3-chloro-2-chloromethyl-propene: A barbier-type practical alternative to the trimethylenemethane dianion

Abstract The reaction of equimolar amounts of 3-chloro-2-chloromethylpropene (2) and a carbonyl compound (3) with an excess of lithium powder and a catalytic amount (6%) of naphthalene in tetrahydrofuran at −78°C leads, after hydrolysis with water, to the corresponding diols 4 in a Barbier-type process.

Arene-catalysed lithiation reactions with lithium at low temperature

The reaction of functionalized alkyl chlorides or phenyl sulphides with an excess of lithium powder in the presence of a catalytic amount of an arene (1%; naphthalene, biphenyl, 4,4′-di-tert-butylbiphenyl) in tetrahydrofuran (THF) at –78 °C gives the corresponding organolithium compounds, which react with electrophiles such as water, iso-butyraldehyde, or cyclohexanone to yield the expected reaction products.

Naphthalene-catalysed lithiation of functionalized chloroarenes : regioselective preparation and reactivity of functionalized lithioarenes

Abstract The lithiation of different functionalized chloroarenes (dichlorobenzenes 1 and 3, mono and dichlorophenols 9 and 14, and chloropivalanilides 18) in the presence of a catalytic amount of naphthalene leads to the corresponding functionalized lithioarenes, which react with electrophiles to give the expected polyfunctionalized aromatic molecules 2, 4, 10, 19, 21, 22 and 24 in a regioselective manner. In the case of starting from chlorinated phenols or anilides a deprotonation of the functional group is carried out prior to the lithiation process; only for 2-chloropivalanilide 18o a coupling reaction leading to 2-n-butylpivalanilide is observed when an excess of n-butyllithium is used in the deprotonation step.

Arene-catalysed reductive lithiation of tetrahydrofuran: improved synthesis of 1,5-diols

The reductive cleavage of tetrahydrofuran at −78°C can be easily achieved by using an excess of lithium powder in the presence of BF3·OEt2 and a catalytic amount (<8%) of an arene (naphthalene, biphenyl, 4,4′- di-tert-butylbiphenyl or anthracene), the best results being obtained with naphthalene. The dianion prepared by this method reacts with carbonyl compounds yielding 1,5-diols.

New masked δ-lithiocarbonyl compounds: preparation and synthetic applications☆

Abstract The reaction of 2-(4-chlorobutyl)-1,3-dioxolanes (1a–c) or 2-(4-chlorobutyl)-2-ethyl-1,3-dithiane (1d) with an excess of lithium powder and a catalytic amount of naphthalene (8 mol %) in THF at -78°C leads to a solution of the corresponding masked lithium δ-enolates 2, which react with different electrophiles (water, deuterium oxide, carbonyl compounds, carboxylic acid derivatives, dibenzyl disulfide or benzylideneaniline) to yield the expected products 3–15. In the presence of a catalytic amount of CuBr.Me2S the intermediate 2a reacts with cyclohex-2-enone giving the compound 16a through a conjugate addition. The deprotection of compounds 10a, 12a, 16a and 4b–6b with 2 N HCl gives the expected functionalized carbonyl compounds 17a–19a and 20b–22b, respectively. Finally, using silicon reagents it is possible to prepare alcohols 20a–25a, dienic alcohols 26a–29a and cyanooxepanes 30a–33a from the in situ generated hydroxyaldehydes of the type 17a with triethylsilane, allyltrimethylsilane and trimethylsilyl cyanide, respectively.