Miguel Yus

First enantioselective addition of dialkylzinc to ketones promoted by titanium(IV) derivatives

Abstract The reaction of dimethyl or diethylzinc with ketones in the presence of a stoichiometric amount of titanium tetraisopropoxide and a catalytic amount (20 mol %) of camphorsulfonamide derivatives as chiral ligands leads to the formation of the corresponding enantioenriched alcohols with enantiomeric ratios up to 94.5:5.5, the best results being obtained when phenones are used as substrates independently of the zinc reagent.

Reductive deprotection of allyl, benzyl and sulfonyl substituted alcohols, amines and amides using a naphthalene-catalysed lithiation

Abstract The reaction of different protected alcohols, amines and amides with lithium and a catalytic amount of naphthalene (4 mol %) in THF at low temperature leads to their deprotection under very mild reaction conditions, the process being in many cases chemoselective.

First enantioselective addition of diethylzinc and dimethylzinc to prostereogenic ketones catalysed by camphorsulfonamide-titanium alkoxide derivatives

Abstract The reaction of diethylzinc or dimethylzinc with prostereogenic ketones, in the presence of a stoichiometric amount of titanium tetraisopropoxide and a catalytic amount (20%) of camphorsulfonamide derivatives as chiral ligands leads to the formation of the corresponding enantioenriched tert-alcohols with enantiomeric ratios up to 94.5 : 5.5. The best results were obtained when phenones are used as substrates independently of the dialkylzinc reagent. The enantioselectivity shows a linear relationship with the enantiomeric excess of the ligand and seems to be independent of the reaction yield. A tentative catalytic cycle and mechanistic model are proposed for this new reaction.

Camphorsulfonamide derivatives: a new class of chiral catalysts for the titanium alkoxide-promoted addition of dialkylzinc to aldehydes

Abstract The enantioselective addition of dialkylzinc to several aldehydes, using different chiral bidentate ligands ( 3a-j, 4a-h ) [derived from (+)-10-camphorsulfonyl chloride] and titanium alkoxide as catalysts, is studied. The influence of temperature, titanium alkoxide, stoichiometry, additive, aldehyde and ligand structure is also studied.

Imidoyllithiums: Masked acyllithium reagents

Abstract The reaction of chloroimines 1 with an excess of lithium powder and a catalytic amount of naphthalene (4 mol %) in THF at −78°C leads to the corresponding imidoyllithium intermediates 2 , which by treatment with different electrophiles [Pr i CHO, Bu t CHO, n -C 5 H 11 CHO, PhCHO, Et 2 CO, (CH 2 ) 5 CO, EtOCOCl, MeOCSCl, n -C 7 H 15 CON(Me)OMe] at −78 to 20°C and final hydrolysis with water affords functionalysed imines 3 . For starting material 1a is necessary to filter off the excess of lithium at the end of the lithiation step in order to get compounds 3 , without filtration amines 4 are the reaction products isolated. Hydrolysis of compounds 3 either during chromatographic purification or by acidic hydrolysis (2 N HCl, THF) gives the expected functionalised ketones 5 .

Generation of allylic and benzylic organolithium reagents from the corresponding ester, amide, carbonate, carbamate and urea derivatives

Abstract The reaction of different allylic and benzylic non-enolisable esters or amides (1), carbonates (4), carbamates (6, 7) and ureas (8) with an excess of lithium powder and a catalytic amount of naphthalene (10%) in the presence of an electrophile [iPrCHO, tBuCHO, PhCHO, Me2CO, Et2CO, (CH2)5CO, Ph2CO, Me3SiCl] in THF at different temperatures (−78, −30 or 0°C) leads, after hydrolysis with water, to the corresponding allylated or benzylated products (2).

Imidoyl chlorides as starting materials for the preparation of masked acyllithium intermediates: synthetic applications

Abstract The lithiation of several imidoyl chlorides 5, catalysed by substoichiometric amounts of naphthalene, followed by reaction with different electrophiles gives, after hydrolysis, the corresponding imine derivatives 6 and 9 or amines 7, depending on the reaction conditions. The imine derivatives are easily converted into the corresponding ketones by treatment either with dilute hydrochloric acid, for N-aryl derivatives, or with silica gel, for N-alkyl derivatives. The hydroxyimines obtained react with LiAlH4 to give the corresponding 1,2-aminoalcohols, as a single diastereoisomer. The same result is found when the imine moiety is in situ reduced with lithium. The 1,2-aminoalcohols obtained are easily transformed into the corresponding 1,3-oxazolidines 11 by reaction with para-formaldehyde under acidic catalysis.

Naphthalene-catalysed lithiation of carbamoyl and thiocarbamoyl chlorides under Barbier-type reaction conditions

The reaction of different carbamoyl or thiocarbamoyl chlorides 1 with carbonyl compounds or imines 2 in the presence of an excess of lithium powder and a catalytic amount of naphthalene (3 mol %) in THF at −78°C leads, after hydrolysis with water, to the expected α-hydroxy or α-amino amides 3, respectively. In the case of allylic or benzylic derivatives 1a,c, when longer reaction times are used, the corresponding products 4 resulting from a deallylation or debenzylation are obtained. The use of DMF or phenyl isocyanate as electrophiles affords substituted oxamides 5. Finally, when previously to the hydrolysis an excess of an alkyl chloride is added to the reaction mixture, 1,2-diols 6 are formed, resulting from a final double addition of the in situ generated alkyllithium to the α-hydroxy amide initially formed.

Arene-catalysed lithiation of triflates and triflamides under barbier-type conditions: An indirect transformation of alcohols and amines into organolithium compounds

Abstract The reaction of alkyl triflates 1 or allyl or benzyl triflamides 3 with an excess of lithium powder and a catalytic amount of naphthalene (4 mol %) in the presence of different electrophiles [Me 3 SiCl, Pr i CHO, Bu t CHO, PhCHO, 4-MeOC 6 H 4 CHO, CH 3 (CH 2 ) 6 CHO, Et 2 CO, (CH 2 ) 5 CO, ( c -C 3 H 5 ) 2 CO, PhCOMe, 4-MeC 6 H 4 COPh, PhCH=NPh, n -C 8 H 7 CON(CH 2 ) 4 ] in THF at temperature ranging between −78 and 0°C leads, after hydrolysis with water, to the corresponding condensation products 2 . When α,β-unsaturated carbonyl compounds are used as electrophilic compounds 1,2- (2-cyclohexenone) or 1,4-addition (cinnamaldehyde or benzylideneacetone) takes places depending on the electrophile used.

Naphthalene-catalysed lithiation of N,N-diisopropylbenzamide and its methoxy derivatives

Abstract The reaction of N , N -disubstituted benzamide derivatives 1 with lithium and a catalytic amount of naphthalene (4 mol %) in the presence of carbonyl compounds (Barbier-type conditions) led to the formation of the corresponding 3,4-dihydro-4-substituted benzamides 2 . The presence of a 4- tert -butyl group in the starting benzamide changed the position of the electrophilic fragment to give the 3,4-dihydro-3-substituted amide 3 . When the reaction was performed with the corresponding methoxybenzamides 7 , only reductive demethoxylation took place, giving (by reaction with carbonyl compounds) the corresponding substituted benzamides 8 .