Balbino Mancheño

Naphthalene-catalysed lithiation of allylic and benzylic mesylates: a new method for allyl, methallyl, and benzyl lithium

Abstract The reaction of allylic or benzylic mesylates ( 1 with an excess of lithium powder and a catalytic amount of naphthalene (4 mol %) in THF at −78°C leads to a solution of the corresponding organolithium derivatives, which by treatment with different electrophiles yield the expected products 2–7 . As an alternative route, the process can be carried out at 0°C by adding the corresponding mesylate together with the electrophile to a suspension of the activated lithium in THF, in a Barbier-type reaction.

Naphthalene-catalysed lithiation of dialkyl sulfates : a new route for organolithium reagents

Abstract The lithiation of primary and secondary dialkyl sulfates with an excess of lithium powder in the presence of a catalytic amount of naphthalene at −78°C leads to the corresponding alkyl-lithium reagents (1:2 molar ratio), which react with different electrophiles, mainly carbonyl compounds, to yield the expected coupling products. This methodology represents an indirect way for transforming alcohols into organolithium compounds through the corresponding dialkyl sulfates.

C,O-Dilithiated Diarylmethanols: Easy and Improved Preparation by Naphthalene-Catalysed Lithiation of Diaryl Ketones and Reactivity Toward Electrophiles

Abstract The lithiation of different diaryl ketones 1 with an excess of lithium powder and a catalytic amount (8 mol %) of naphthalene in tetrahydrofuran at −30°C leads to the formation of the corresponding dianions of the type I, with Met=Li, which react with several electrophiles (E+=MeI, EtBr, PriCHO, PhCHO, cyclohexanone, MeCN) to give, after hydrolysis, the expected substituted diarylmethanols 2.

Direct transformation of trialkyl phosphates into organolithium compounds by a DTBB-catalysed lithiation

Abstract The reaction of different alkylic or phenylic phosphates 1 with an excess of lithium powder and a catalytic amount of DTBB (5 mol %) in the presenc

Lithiated β-aminoalkyl sulfones as mono and dinucleophiles in the preparation of nitrogen heterocycles: Application to the synthesis of capsazepine

Abstract The lithiation of N -benzyl- β -tosylethanamine ( 10a ) and N -benzyl- α -phenyl- β -tosylethanamine ( 10b ) with n -butyllithium at −78°C leads to monoanions 11a and 11b , respectively. Intermediates 11 react with different monoelectrophiles (D 2 O, alkyl halides, and carbonyl compounds) at the α-position with respect to the sulfone, and with dielectrophiles (1,3-, 1,4-dihalides, α-bromoacetates, and α-chloroketones) to afford the corresponding 6, 7, and 5-membered nitrogen heterocycles. The benzoazepine derivative 13ae , obtained by reaction of 11a with 4,5-bis(chloromethyl)-1,2-dimethoxybenzene, are transformed into the inmediate precursor 24 of capsazepine 25 an antagonist of the sensory neuron excitants capsaicin and resiniferatoxin. Cyclic β-amino sulfone: N -benzyl-3-tosylpiperidine ( 13aa ) suffers lithiation at the axial position reacting with electrophiles to give compounds 27 . In the case of the Michael addition to methyl crotonate the corresponding adducts are converted into 1-azabicyclo[3.3.1]nonan-2-one derivatives. Finally, base-induced dehydrosulfinylation, reductive desulfonylation, and Julias methylenation are studied with some representative derivatives.

Direct transformation of dialkyl sulfates into alkyllithium reagents by a naphthalene-catalysed lithiation

Abstract The lithiation of primary and secondary dialkyl sulfates with an excess of lithium powder in the presence of a catalytic amount of naphthalene (4 mol %) in THF at −78°C leads to the corresponding alkyllithium reagents (1:2 molar ratio) which react with different electrophiles, mainly carbonyl compounds, to yield after hydrolysis, the expected coupling products. This methodology represents an indirect way to transform alcohols into organolithium compounds through the corresponding dialkyl sulfates. When the same procedure is applied to five or six member cyclic sulfates (derived from 1,2- or 1,3-diols) only products arising from a β- or γ-elimination process (giving olefins or cyclopropanes), respectively, are obtained.

Asymmetric synthesis of α-amino acids from α,β-(Z)-didehydroamino acid derivatives with 1,2,3,6-tetrahydropyrazin-2-one structure

Abstract Chiral (Z)-α,β-didehydroamino acid (DDAA) derivatives 14, 15 and 16 are obtained from a new chiral iminic cyclic glycine template with 1,2,3,6-tetrahydropyrazin-2-one structure 10 by condensation with carbonyl compounds, Eschenmosers salt and Brederecks reagent, respectively. The didehydroalanine derivative 15 and the enaminone 16 can give DDAA derivatives 14 using Heck olefination and vinylic nucleophilic substitution. These DDAA derivatives 14 and 15 undergo diastereoselective cyclopropanation, 1,3-dipolar and Diels–Alder cycloaddition reactions giving, after hydrolysis, the corresponding cyclic and bicyclic α-amino acids.

Simple synthesis of α-methylene esters and amides from methacrylic derivatives via tosylated intermediates

Abstract ∝-(Tosylmethyl)acrylic acid methyl ester or N -isopropylamide (obtained by a tandem iodosulfonylation-dehydroiodination of methyl methacrylate or N -isopropylacrylamide) react with Grignard reagents or sodium diethyl malonate to give the corresponding ∝-methylene esters or amides in a regioselective manner.

Coumarins and ferulol esters from Cachrys sicula

Abstract (−)-Sprengelianin, (−)-prantschimgin and other minor coumarins were isolated from the roots and/or the umbels of Cachrys sicula . The roots also afforded the monoterpene hydroxyaldehyde ferulol esterified to angelic, tiglic and senecioic acids. The (−)-enantiomer of sprengelianin (2′ S ) had not been reported previously. The coumarins saxalin and pabulenol and the aromatic aldehyde 2,3,4-trimethylbenzaldehyde were also identified but these substances are presumably artefacts.

Lithiomethyl ethyl ether from chloromethyl ethyl ether via a DTBB-catalysed lithiation

Abstract The reaction of equimolecular amounts of chloromethyl ethyl ether ( 1 ) and a carbonyl compound [Bu n CHO, Bu t CHO, PhCHO, Pri 2 CO, Bu t 2 CO, (CH 2 ) 4 CO, 2-cyclohexenone, PhCOMe] with an excess of lithium powder (1:7 molar ratio) and a catalytic amount of DTBB (5 mol %) in THF at 0°C (Method A) leads, after hydrolysis, to the corresponding hydroxyethers 2 . The reaction can be also carried out in a two-step process: tandem lithiation at −90°C and reaction with the electrophile [Bu n CHO, (CH 2 ) 4 CO, PhCOMe, PhMe 2 SiCl, CO 2 , PhCN, PhCONMe 2 , CyNCO, PhNCHPh] at −90 to −60°C (Method B).