Juan Almena

1,2-Di(lithiomethyl)benzene from phthalan: Sequential introduction of two different electrophiles☆

Abstract The reaction of phthalan ( 1 ) with an excess of lithium powder and a catalytic amount of DTBB (2.5 mol %) in THF at 20°C followed by treatment with electrophiles (D 2 O, CO 2 and carbonyl compounds) at −78°C leads, after hydrolysis, to the corresponding functionalised benzylic alcohols 3a-g . When the lithiation reaction is continued, after the reaction with the first electrophile, and a second electrophile (H 2 O, D 2 O and carbonyl compounds) is added, the corresponding disubstituted compounds 6a-q are prepared. Diols 3c-g and 6h,i,l,n and hydroxyacids 6a,c,f,k are easily dehydrated to the corresponding cyclic ethers ( 7c-f, 8h,i,l,n ) or lactones ( 9a,c,f,k ), respectively. Finally, alcohols 6b,d,e give, after acid treatment, the Friedel-Crafts type benzocyclopentenes 10b,d,e .

Naphthalene-catalysed reductive opening of aziridines with lithium: A direct preparation of n-lithio-2-lithioalkylamines

Abstract The reductive opening of N -phenylaziridine ( 1 ) with an excess of lithium presence of a catalytic amount (5 molar %) of naphthalene at −78°C leads to the corresponding N -lithio-2-lithioethylamine ( 2 ), which by reaction with different electrophiles (water, deuterium oxide, dimethyl disulphide, pivalaldehyde or cyclohexanone) affords the expected product ( 3 ). The same process applied to N -cyclohexylaziridine fails. The reactions also works with the chiral aziridine 4 yielding the chiral deuteriated amine 5 , through the corresponding chiral dianionic intermediate.

Lithium 2-(2-lithiomethylphenyl)ethanolate from isochroman: Easy preparation of substituted benzoxepines and functionalised arenes

Abstract The reaction of isochroman (1) with an excess of lithium powder and a catalytic amount of DTBB (2.5 mol %) in THF at 20°C yields the title intermediate, which by reaction with different electrophiles (H2O, D2O, CO2 and carbonyl compounds) at temperatures ranging between −78 and 20°C yields, after hydrolysis, the corresponding products 3. Diols 3h-m, derived from benzaldehyde or ketones, give upon treatment with 85% phosphoric acid the corresponding benzoxepines 5h-m. In the other cases, Friedel-Crafts products resulting from a rearrangement of the first carbenium ion formed, are obtained.

4,4′-Di-tert-butylbiphenyl-catalysed reductive opening of azetidines with lithium: A direct preparation of 3,N-dilithioalkylamines

Abstract The reaction of N-phenylazetidine 1a with an excess of lithium powder and a catalytic amount of 4,4′-di-tert-butylbiphenyl (5 mol %) in THF at −15°C leads to the corresponding dianion 2a, which by treatment with different electrophiles (H2O, D2O, ButCHO, PhCHO, ( CH 2 ) 5 C O, PhCHNPh, CO2) yields, after hydrolysis with water, the expected functionalysed amines 3aa-ah. The same method applied to N-isopropyl-2-phenylazetidine 1 c affords compounds 3ca-ce (electrophiles: H2O, D2O, PhCHO, Me2CO, CH2CHCH2Br) resulting from the more stable benzylic intermediate 2c. Finally, the regiochemistry in the reductive opening of 2-methyl-N-phenylazetidine 1d followed by deuterolysis was studied: a mixture of both regioisomers 3da+3da′ was obtained, the ratio being the oposite as expected according to the stability of both intermediates 2d and 2d′.

Reductive opening of phenyl substituted thiacycloalkanes: New way for sulphur-containing organolithium compounds

Abstract The reaction of 2-phenyl substituted four, five and six membered thiacycloalkanes (1, 4 and 7) with lithium and a catalytic amount of DTBB (5 mol %) in THF at −78°C leads to the corresponding sulphur-containing benzylic organolithium compounds (2, 5 and 8), which by reaction with different electrophiles [D2O, Me3SiCl, ButCHO, Me2CO, Et2CO, (CH2)4CO, CO2] followed by hydrolysis with water afford the expected functionalised mercaptans (3, 6 and 9) in a regioselective manner. Some reaction products (3, 6) are cyclised under acidic conditions (85% phosphoric acid) to yield the corresponding homologous substituted sulphur-containing saturated heterocycles (10, 11).

Nitrogen-containing remote functionalised organolithium compounds by reductive opening of five- and six-membered heterocycles

Abstract The reaction of different five- or six-membered nitrogen-containing heterocycles such as N -isopropyl-2-phenylpyrrolidine ( 1 ), N -phenyl-3-pyrroline ( 6 ), N -phenylisoindoline ( 10 ), N -phenyltetrahydroisoquinoline ( 13 ) and N -methyltetrahydroisoquinoline ( 19 ) with an excess of lithium powder and a catalytic amount of DTBB (4.5 mol %), followed by treatment with electrophiles [H 2 O, D 2 O, MeI, CH 2 CHCH 2 Br, Pr i CHO, Bu t CHO, PhCHO, Me 2 CO, Pr n COMe, PhCOMe, (CH 2 ) 4 CO, (CH 2 ) 5 CO, CO 2 ] and final hydrolysis gives a wide series of functionalised amines 3, 8, 9, 12 and 19 , the key step in the process, being the reductive opening of the starting material giving a dianionic remote functionalised organolithium compound.

NEW HOMOLOGATION OF 2-HYDROXY AND 2-MERCAPTO BENZYLIC ALCOHOLS

Abstract The reaction of benzo-1,3-dioxanes or benzo-1,3-oxathianes 1 [easily prepared from 2-hydroxy or 2-mercapto benzylic alcohols (3 or 4, respectively) and carbonyl compounds] with an excess of lithium and a catalytic amount of DTBB (4.5 mol %) in THF at room temperature or −78°C leads, after hydrolysis with water, to the corresponding homobenzylic alcohols 2. Cyclisation of compounds 2 under acidic (85% H3PO4) or neutral (Ph3P/DIAD) conditions affords the expected heterocycles 5.