Fernando F Huerta

DTBB-catalysed lithiation of chlorinated benzylic chlorides, alcohols, thiols or amines

The reaction of chlorinated benzyl chlorides (1) with an excess of lithium powder and a catalytic amount of DTBB (4 mol %) in the presence of different electrophiles [PriCHO, ButCHO, Et2CO, (CH2)5CO, PhCOMe, Me3SiCl] in THF at −50°C followed by hydrolysis with water leads to the corresponding compounds 2. When the same DTBB-catalysed lithiation is applied to several chlorinated benzylic alcohols or mercaptans (4 or 5) it is necessary to deprotonate the starting material with BunLi; treatment of the resulting anions or amine 6 as above, but at −78°C, leads to the expected reaction products 8, after reaction with different electrophiles [PriCHO, ButCHO, Et2CO, (CH2)5CO, PhCOMe, Me3SiCl] and final hydrolysis with water.

DTBB-catalysed lithiation of 2,3-dichloropropene and related chloroamines: Synthetic applications

Abstract The reaction of 2,3-dichloropropene ( 1 ) and different carbonyl compounds ( 2 ) with an excess of lithium powder (1:7 molar ratio) in the presence of a catalytic amount of DTBB (5 mol %) in THF at 0°C leads, after hydrolysis with water, to the corresponding methylenic 1,4-diols 3 in a Barbier-type process. The cyclisation of diols 3 under acidic conditions (hydrochloric or phosphoric acid) yields the corresponding substituted methylenic tetrahydrofurans 4 . Finally, 2,3-dichloropropene ( 1 ) is converted into the corresponding allylic chloroamines 5 and then submitted to the tandem naphthalene-catalysed 2lithiation-S E reaction with different electrophiles affording the corresponding functionalised amines 7 . The last process fails for oxygen- or sulfur-containing chloroallylic materials 8 .

Lithiated benzyllithiums from chlorobenzyl chlorides by a DTBB-catalysed lithiation

Abstract The reaction of 2-, 3- or 4-chlorobenzyl chlorides ( 1a-c ) with an excess of lithium and a catalytic amount of DTBB (7 mol%) in the presence of different electrophiles [Pr i CHO, Bu t CHO, Et 2 CO, (CH 2 ) 5 CO, PhCOMe, Me 3 SiCl] in THF at −50°C leads after hydrolysis with water, to the expected dioles or disilylated compounds 2aa-2cf .

DTBB-catalysed lithiation of 6-chloro-1-hexene and related systems: synthetically useful temperature-dependent behaviour †

The reaction of 6-chloro-1-hexene 1 with lithium powder and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB, 5% molar) in THF at −78°C gives the corresponding organolithium intermediate 2, which by reaction with different electrophiles [ButCHO, PhCHO, Et2CO, (CH2)5CO, PhCOMe] affords, after hydrolysis with water, the expected products 3. The same reaction performed at −30°C gives cyclopentyl derivatives 5, probably by cyclisation of the open-chain intermediate 2 to give the cyclic organolithium compound 4. For the tertiary derivative 6, only the cyclic compound 10 could be isolated at −30°C due to the great instability of the corresponding tertiary organolithium intermediate 7, which undergoes a proton abstraction even at −78°C. From allyl 2-chloro-phenyl ether 11 only the corresponding cyclic compound 14 was isolated either at −78°C or at −30°C. In all cases a carbanionic cyclisation, better than a radical one, is postulated to occur.

Naphthalene-catalysed lithiation of 2-(chlorophenyl)-1,3-dioxolanes: Generation of formyl- and acetyl-phenyllithium equivalents [1]

Abstract The reaction of 2-(chlorophenyl)-1,3-dioxolanes 1 with an excess of lithium powder and a catalytic amount of naphthalene (5 mol %) in the presence of different carbonyl compounds [ t BuCHO, Et 2 CO, (CH 2 ) 5 CO, PhCOMe] as electrophiles (Barbier-type conditions) in THF at −78°C leads, after hydrolysis with water at the same temperature, to the expected products 3 , the corresponding intermediates involved being formyl- or acetyl-phenyl anion equivalents.

Ketalised 3,4-dihydroxybutyllithiums: New intermediates to transfer four-carbon diol functionality to electrophilic reagents

Abstract The reaction of ketalised 1-chlorobutane-3,4-diol 1a,b with lithium powder and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB, 4 mol %) in the presence of an electrophile [PriCHO, ButCHO, PhCHO, PrnCOMe, (CH2)5CO] at −78°C in THF (Method A: Barbier-type conditions) leads, after hydrolysis, to the formation of the corresponding ketalised reaction products 2aa-bf. Alternatively, the reaction can be carried out in a two-step process (Method B), which implies first a DTBB-catalysed lithiation folowed by reaction with an electrophile [Me3SiCl, PriCHO, ButCHO, PhCHO, Me2CO, Et2CO, PrnCOMe, (CH2)5CO, PhCOMe] both steps being performed at −78°C. When the starting materials are chiral, this methodology allows the preparation of chiral protected di or triols in a nondiastereoselective manner.

DTBB-catalysed lithiation of 4-functionalised 1-chloro-2-butenes

Abstract The reaction of N , N -disubstituted ( E )-4-amino-1-chloro-2-butenes 1 with an excess of lithium and a catalytic amount of DTBB in the presence of an electrophile [E + = Bu t CHO, PhCHO, Me 2 CO, (CH 2 ) 5 CO, ( c -C 3 H 5 ) 2 CO, Me 3 SiCl] in THF at −78°C leads, after hydrolysis with water, to the expected mixture of 1,2- and 1,4- disubstituted compounds ( 2 and 3 , respectively), which could be easily separated by flash chromatography. When the reaction was applied either to the corresponding ( Z )-starting materials or to ( Z )- or ( E )-oxygen or sulfur containing chlorinated 2-butenes the yields are poorer than for nitrogenated precursors.

Functionalised propargyllithium reagents

Abstract The reaction of chlorinated acetylenic ether or amines 1 with lithium and a catalytic amount of DTBB (5%), in the presence of different electrophiles [PriCHO, BulCHO, PhCHO, Me2CO, (CH2)5CO, Me3SiCl] in THF at −78 or −105°C leads, after hydrolysis with water, to the corresponding products 2. The same process applied to the previously deprotonated chloroalcohol 4a or the secondary amine 4b can be carried out in a two-step reaction giving the expected products 6 by using several electrophiles [PriCHO, ButCHO, PhCHO, Me2CO, (CH2)5CO, Me3SiCl] at −78°C.

DTBB-CATALYSED LITHIATION OF 3-FUNCTIONALISED 1-CHLOROPROPENES

Abstract The reaction of different 3-chlorinated allyl amines 1a,b or phenylether 1c with an excess of lithium powder, a catalytic amount of DTBB (5 mol %) and an electrophile [PriCHO, ButCHO, Et2CO, (CH2)5CO] in THF at −78°C gives, after hydrolysis with water, the expected Z E mixture of the corresponding products 2. The corresponding two-step process at temperatures ranging between −30 and −40°C [electrophiles: PriCHO, ButCHO, (CH2)5CO] yields propargylic derivatives 3. A mechanistic explanation for this behaviour is given.

Di(lithiomethyl)benzenes from di(chloromethyl)benzenes by a DTBB-catalysed lithiation under Barbier-type conditions

Abstract The reaction of 1,2-, 1,3- and 1,4-di(chloromethyl)benzenes (1a-c) and different electrophiles [PriCHO, ButCHO, PhCHO, (CH2)5CO, PhCOMe, Me3SiCl] with an excess of lithium powder and a catalytic amount of DTBB (4 mol%) in THF at 0°C leads, after hydrolysis with water, to the expected dioles or disilylated compounds 2aa-cf.