Lithio Derivative Research Articles

4-lithiosydnone imines: Generation and stability. Plant growth regulating activity of 4-hydroxymethyl derivatives of sydnone imines

The C(4)-deprotonation of N6-substituted sydnone imines with lithium hexamethyldisilazide (LHDMS), lithium diisopropylamide (LDA), lithium diethylamide (LDEA), and n-BuLi was studied. A thermal stability of 4-lithiosydnone imines was investigated and an efficiency of subsequent reactions of the generated C(4)-lithio derivatives with electrophiles was shown to depend on the exploited deprotonating reagent. It was found that 4-(α-arylhydroxymethyl)sydnone imines, when used for pre-sowing treatment of corn seeds at very low doses (0.25-5 g t−1), promoted a plant growth up to 60%.

α-Deprotonation of a β-shielded acrylamide creates a distorted lithium 1-aminoallen-1-olate

The β-shielded acrylamide N,N-diisopropyl-α-(1,1,3,3-tetramethylindan-2-ylidene)acet-amide was prepared through ketone addition of an α-lithiated acetamide, followed by H2O elimination. Its α-deprotonation by n-butyllithium occurred readily in THF without any tendency towards addition reactions at C=O or C-β. The resultant single crystals of a dimeric lithio derivative had triple Li–O coordination and a weakly bonding, ion-pair type Li–C(α) relationship. In tert-butyl methyl ether as the solvent, up to seven pairs of diastereotopic nuclei (both 1H and 13C) established a CS-symmetric lithium 1-aminoallen-1-olate structure that is ascribed to either a thermal ground state or a very rapid (on the NMR time scales) oscillation between two chiral ground states that may resemble the solid-state structure.

Functionalization of Oxazolo[4,5‐b]pyrazines by Deprotometallation

Different 2‐arylated oxazolo[4,5‐b]pyrazines, obtained by palladium(II)‐catalyzed domino reaction from 2,3‐dichloropyrazine and the corresponding carboxamides, were functionalized by deprotometallation. Employing lithium 2,2,6,6‐tetramethylpiperidine, in order to form a lithio derivative, and then trapping it by iodolysis, proved to be inefficient. However, the presence of a zinc‐based in situ trap allowed most substrates to be functionalized. Deprotonation of the pyrazine ring was observed in the presence of tolyl and anisyl groups at the oxazole 2‐position. In contrast, with chlorophenyl and thienyl groups in this 2‐position, deprotonation rather occurred on these groups either competitively or exclusively. The regioselectivities were discussed in the light of calculated pKa values of the substrates in THF. Finally, in the case of 2‐phenyloxazolo[4,5‐b]pyrazine, we converted the mixture of 5‐ and 6‐iodinated products into the corresponding 5,6‐diiodide, which was further functionalized by a double Suzuki coupling.

Formation of propanedithioamide and 1,2-dithiole derivatives from reaction of the lithio derivative of 1-phenylthiomethyl-3,5-dimethylpyrazole with PhNCS and coordination behavior of propanedithioamide on tungsten carbonyl

Treatment of 1-phenylthiomethyl-3,5-dimethylpyrazole with n-butyllithium, and subsequently with phenyl isothiocyanate yielded 2-(3,5-dimethylpyrazol-1-yl)-2-(phenylthio)thioacetanilide, 2-(3,5-dimethylpyrazol-1-yl)thioacetanilide, N,N′-diphenyl-2-(3,5-dimethylpyrazol-1-yl)propanedithioamide and 5-anilino-4-(3,5-dimethylpyrazol-1-yl)-3-phenylimino-1,2-dithia-4-cyclopentene, respectively. Reaction of the propanedithioamide derivative with W(CO)5THF has been investigated, which gave a bis(chelate) tungsten complex through two relatively soft sulfur atoms. All these newly synthesized compounds were characterized by NMR and HRMS spectroscopy (or elemental analysis), and their structures were unambiguously confirmed by X-ray crystallography. Two possible pathways, including a carbanion or a carbene intermediate formed via the CS bond cleavage, have been suggested to explain the formation of propanedithioamide and 1,2-dithiole derivatives.

Thiophene‐Fused 3‐Methylene‐2,3‐dihydrochalcogenophenes: Fluorescent Dyes Incorporated in a Rigid Dibenzobarrelene Skeleton

ABSTRACT3‐Methylene‐2,3‐dihydrothienothiophene and ‐selenophenothiophene derivatives incorporated in a rigid dibenzobarrelene skeleton were synthesized by intramolecular Diels–Alder reaction, and their structures, fluorescent properties, and electrochemistry were elucidated. In 3‐methylene‐2,3‐dihydrothieno[3,2‐b]thiophene derivatives, silyl and phenyl substituents at the terminal position were effective for strong blue fluorescence (λem = 412–455 nm) with high quantum yields (ΦF = 0.65–0.99), whereas the unsubstituted parent compound was weakly fluorescent (λem = 338 nm, ΦF = 0.03). The phenyl‐substituted [3,2‐b]‐derivative showed strong emission also in the solid state (ΦF = 0.70). The corresponding [2,3‐b]‐isomer showed blueshifted absorption (λabs = 342 nm) and emission (λem = 436 nm) maxima with low‐to‐moderate quantum yields in solution (ΦF = 0.24) and in the solid state (ΦF = 0.41). In the case of the selenium congeners (3‐methylene‐2,3‐dihydroselenopheno[3,2‐b]thiophene derivatives), the heavy atom effect due to the selenium was decisive to decrease the quantum yields (ΦF = 0.01–0.06). The oxidation of phenyl‐substituted [3,2‐b]‐derivative yielded the corresponding sulfoxide and sulfone, which showed strong emission at around 440 nm with high quantum yields in dichloromethane (ΦF = 0.91 and 0.98, respectively). A dimer of the phenyl‐substituted [3,2‐b]‐derivative was prepared by oxidative coupling of the lithio derivative. The dimer had weak redshifted emission (λem = 547 nm, ΦF = 0.10) and showed a reversible cyclic voltammogram with E1/2 = 0.35 V versus Fc/Fc+ redox couple.

ChemInform Abstract: Synthesis of 4‐Unsubstituted 2H‐1,2,3‐Benzothiadiazine 1,1‐Dioxides via ortho Lithiation of Protected Benzaldehyde Derivatives.

Abstract Variously substituted 2-phenyl-1,3-dioxolanes and 2-(2-bromophenyl)-1,3-dioxolanes, prepared from the corresponding benzaldehydes, were lithiated ortho to the acetal group. Reaction of the lithio derivatives with sulfur dioxide led to the lithium sulfinate salts, which gave, upon oxidative chlorination with sulfuryl chloride, the corresponding benzenesulfonyl chlorides. Then, depending on the aromatic substitution pattern of the molecule, several protocols were elaborated for the functional group transformations leading to the target compounds. Ring closure was performed with hydrazine hydrate or acetylhydrazine, in the latter case with one-pot removal of the acetyl group. The 4-unsubstituted 2H-1,2,3-benzothiadiazine 1,1-dioxides thus obtained are potential drug candidates based on their structural similarity to biologically active phthalazinones.

Synthesis of 4-unsubstituted 2H-1,2,3-benzothiadiazine 1,1-dioxides via ortho lithiation of protected benzaldehyde derivatives

Variously substituted 2-phenyl-1,3-dioxolanes and 2-(2-bromophenyl)-1,3-dioxolanes, prepared from the corresponding benzaldehydes, were lithiated ortho to the acetal group. Reaction of the lithio derivatives with sulfur dioxide led to the lithium sulfinate salts, which gave, upon oxidative chlorination with sulfuryl chloride, the corresponding benzenesulfonyl chlorides. Then, depending on the aromatic substitution pattern of the molecule, several protocols were elaborated for the functional group transformations leading to the target compounds. Ring closure was performed with hydrazine hydrate or acetylhydrazine, in the latter case with one-pot removal of the acetyl group. The 4-unsubstituted 2H-1,2,3-benzothiadiazine 1,1-dioxides thus obtained are potential drug candidates based on their structural similarity to biologically active phthalazinones.

Coordination of a chiral tin(ii) cation bearing a bis(oxazoline) ligand with tetrahydrofuran derivatives

The reaction of SnCl(2) with the lithio derivative of a bis(oxazoline) ligand precursor afforded the enantiomeric chlorostannylene whose chloride ion can be substituted by several neutral or anionic Lewis donors. Abstraction of the chloride ion from the chlorostannylene with silver salts gave the corresponding tetrahydrofuran (THF) complexes of a chiral tin(ii) cation in 1,2-dimethoxyethane (DME) containing THF. That is, the reaction with silver hexafluoroantimonate (AgSbF(6)) afforded the THF complex without interaction with the counteranion. In contrast, reaction with silver triflate (AgOTf) gave the THF complex whose tin center had a pseudo-trigonal bipyramidal structure with two nitrogen atoms of a bidentate ligand and a lone pair at the equatorial positions and one of the oxygen atoms of triflate and an oxygen atom of THF at the apical positions in the solid state. Use of 3-methyltetrahydrofuran (3-MeTHF) instead of THF afforded the 3-MeTHF complexes, where the R-enantiomer of 3-MeTHF predominantly coordinates to the tin center. The previously reported germanium(II) analogue of the tin(II) cation indicated a similar enantioselectivity for the coordination of 3-MeTHF on the germanium center.

New substituents for the stabilization of low-coordinate germanium species: Use in access to diazogermylenes

The reactions of the P-bis(trimethylsilyl)amino-N-(trimethylsilyl)iminophosphine with various dialkoxydichlorogermanes (alkoxy: OR = OMe, OEt and O i-Pr) at 0 °C led to the stable dichlorogermylene-complexes [(RO) 2P(NSiMe 3)(N(SiMe 3) 2)]GeCl 2 [R = Me ( 1), Et ( 2) and R = i-Pr ( 3)]. The solid-state structure of ( 2) has been determined by X-ray crystallography. A mechanism for the formation of these compounds is proposed, based on the transient species observed in the case of the isopropoxy derivatives. At room temperature in benzene solution, compounds ( 1) and ( 2) eliminate chlorotrimethylsilane without side reactions leading to the corresponding 2,4-diaza-3-phosphagermatidines [(RO) 2P(NSiMe 3) 2]GeCl ( 4) and ( 5), respectively. At the opposite, complex ( 3) showed a modulated behavior: at room temperature, ( 3) still slowly eliminates mainly chlorotrimethylsilane with the formation of [( i-PrO) 2P(NSiMe 3) 2]GeCl ( 6). Structure of this chlorinated germanium(II) compound which can also be seen as a germyl anion has been evidenced by an X-ray analysis. But at higher temperature (40–50 °C) ( 3) mainly decomposes with elimination of isopropylchloride leading to the formation of [( i-PrO)(Me 3SiO)P(NSiMe 3) 2]GeCl ( 7) as a mixture of Z- and E-isomers. The mechanism of this reaction is discussed. The Z-isomer of ( 7) was successfully isolated after a selective crystallization, and investigated by an X-ray analysis. The interconversion mechanism of the two diastereoisomers is also discussed. Reaction of compound ( 5) with the lithio derivative of the trimethylsilyldiazomethane leads to the diazogermylene ( 8), a potential precursor of germa-alkyne.

ChemInform Abstract: An Efficient Synthesis of C-11 Substituted 6H-Pyrido(4,3-b)carbazoles.

Abstract A synthesis of the natural product 5-methyl-6H-pyrido[4,3-b]carbazole-11-methanol, 5 from the ketolactam 7 is described. Compound 7 was treated with one equivalent of MeLi followed by quenching of the reaction mixture with water to give the lactone 19 Compound 19 was treated with a number of organolithium reagents such as methyllithium. n-butyllithium, ethoxyvinyl lithium and the lithio derivative of formaldehyde diethyl mercaptal to give, after sodium borohydride reduction, 1, 15, 30, and 31 respectively. Compounds 30 and 31 were hydrolyzed and then reduced to give compounds 5 and 6 respectively, in an overall yield of 21%. Compounds 16 and 22 were identified as the intermediates in the Saulnier-Gribble synthesis of ellipticine.

ChemInform Abstract: A Direct Synthesis of Olefins by Reaction of Carbonyl Compounds with Lithio Derivatives of 2-(Alkyl- or (2′-Alkenyl)- or Benzylsulfonyl) benzothiazoles.

ChemInform Abstract: A Direct Synthesis of Olefins by Reaction of Carbonyl Compounds with Lithio Derivatives of 2-(Alkyl- or (2′-Alkenyl)- or Benzylsulfonyl) benzothiazoles.

ChemInform Abstract: Mannich/Friedel-Crafts Preparations of 1-(Arylmethyl)benzotriazoles and Synthetic Transformations of Their Lithio Derivatives.

The synthesis of 1-(arylmethyl)benzotriazoles by Mannich type reactions of benzene, toluene, p-xylene and chlorobenzene with 1-chloromethylbenzotriazole in the presence of aluminium halides is reported. Alkylation, of their lithio derivatives followed by the cleavage of benzotriazole from the resulting 1-(α-arylalkyl)benzotriazoles upon reduction with LiAlH4–AlCl3 or elimination by AcOH are shown to be useful procedures for the preparation of substituted arenes. An oxidative coupling of lithiated 1-(arylmethyl)benzotriazoles gave 1,2-diaryl-1,2-di(benzotriazol-1-yl)ethanes. Novel heterocyclic ring fissions of the lithio derivatives of 1-(arylmethyl)benzotriazoles afforded 1,2,4-benzotriazine and 1,2-bis(N-methylanilino)ethene derivatives.

ChemInform Abstract: New Synthesis of Diarylalkynes from 1-(Arylmethyl)benzotriazoles and Arylideneamines.

The Michael addition of lithio derivatives 2 of 1-(arylmethyl)benzotriazoles 1 to arylideneamines 3–5 gave the corresponding 1-(benzotriazol-1-yl)-2-anilino (or tosylamino)-1,2-diarylethanes 6–8. The latter were shown to undergo a double elimination reaction under the action of ButOK in DMF to afford diarylalkynes in high yields.

A Synthetic Equivalent of a Germanone Derivative

AbstractReaction of two molar equivalents of 2,6‐bis(diisopropylaminomethyl)phenyllithium (ArLi) with tetramethoxygermane afforded the colourless crystalline dimethoxy bis[2,6‐bis(diisopropylaminomethyl)phenyl]germane Ar2Ge(OMe)2 (1) in good yield. Treatment of 1 with AgF/H2O led to the fluorohydroxy derivative Ar2Ge(F)OH (2), which was characterized, among other techniques, by single‐crystal structure analysis. The corresponding lithio compound Ar2Ge(F)OLi (3) obtained from 2 by reaction with tBuLi behaves as a synthetic equivalent of the heavier analogue of ketone[Ar2Ge=O, 5]. Germanone 5 could not be isolated even at low temperature due to the impossibility of dissociating it from LiF. Treatment of 3 with various reactants on the basis of the known reactivity of ketones led to the expected products. The reaction of 3 with H2O led, as expected, quantitatively to the germanium gem‐diol Ar2Ge(OH)2 (6) as colourless crystals. Such gem‐diols are scarce compounds and only a few are structurally known; in our case, 6 is stabilized by a hydrogen linkage between the hydrogen atoms of the alcohol functionalities and the nitrogen atoms. Other trapping reactions of 3 were investigated with tBuLi and methanol, and the corresponding germanols Ar2Ge(tBu)OH (7) and Ar2Ge(OMe)OH (8) were isolated after hydrolysis in good yields. Attempts to eliminate LiF from 3 by using the chelating agent 1,4,7,10‐tetraoxacyclododecane (12‐crown‐4) allowed us to isolate lithio complex 9. Generation of germanones from fluorohydroxygermanes and their lithio derivatives appears to be a new promising method. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Enantioselective functionalisation of the C-2′ position of 1,2,3,4,5-pentamethylazaferroceneviasparteine mediated lithiation: potential new ligands for asymmetric catalysis

The s-BuLi-sparteine base combination deprotonated the C-2' position of 1,2,3,4,5-pentamethylazaferrocene and subsequent reaction with a range of electrophiles gave C-2 substituted products in 76-93% yield and approximately 80% ee. The products could be recrystallised to enrich ee's to >90%. Resubjection of the initial addition products ( approximately 80% ee) to the deprotonation conditions led to a kinetic resolution to give products with >90% ee and superior overall yields compared to recrystallisation for the cases where the electrophiles were Ph2CO, MeI and Ph2S2. Transmetallation of the 2-lithiopentamethylazaferrocene ( approximately 80% ee) with ZnCl2 allowed palladium catalysed cross coupling with a variety of C-2 haloaryl, heteroaryl and vinyl groups to give some novel C-2' substituted pentamethylazaferrocene derivatives in 61-77% yield in 80% ee. Potential N,N-chelate ligands were recrystallised to >95% ee. A novel C2-symmetric bis-pentamethylazaferrocene could be synthesised by an iron catalysed oxidative coupling of the enatioenriched C-2 lithio derivative and in the presence of a PhMe-Et2O solvent mixture proceeded in 97% ee.

Protonation of the lithio derivatives of the 1,2,4-tri-phosphaferrocenes, [LiFe(η 4-P 2C 2tBu 2PBu)(η 5-C 5R 5)] (R = H, Me): Crystal and molecular structure of [Fe(η 4-P 3C 2tBu 2BuH)(η 5-C 5Me 5)

A new synthetic route is described to generate the 4-centre-5 electron donor ring system (P 3C 2 t Bu 2BuH), via protonation of the lithium salts [LiFe(η 4-P 2C 2 t Bu 2PBu)(η 5-C 5R 5)] (R = H, Me). The molecular structure of [Fe(η 4-P 3C 2 t Bu 2BuH)(η 5-C 5R 5)] (R = Me) has been determined by a single crystal X-ray study.

Liquid‐Phase Synthesis of Methyl (2Z)‐2‐Arylsulfonylmethyl‐2‐ alkenoates from PEG‐Supportedα‐Phenylselenopropionate

AbstractTreatment of lithio derivative of novel PEG‐supported (‐phenylselenopropionate with aldehydes, followed by oxidation‐elimination with 30% hydrogen peroxide, formed Baylis‐Hillman products, which were then reacted with sodium arylsulfinate. The resulting sulfonylated products were cleaved from the PEG efficiently affording methyl (2Z)‐2‐arylsulfonylmethyl‐2‐alkenoates in good yields and high purities.

Liquid‐Phase Synthesis of Methyl (E)‐2‐Nitromethyl‐2‐alkenoates Based on PEG‐Supported α‐Phenylselenopropionate

The reaction of the lithio derivative of novel polyethylene glycol (PEG)‐supported α‐phenylselenopropionate with aldehydes, followed by oxidation–elimination with 30% hydrogen peroxide and then treatment with sodium nitrite, formed PEG‐bound 2‐nitromethyl‐2‐alkenoates. Subsequent cleavage from the PEG efficiently afforded methyl (E)‐2‐nitromethyl‐2‐alkenoates in good yields and high purities.

A facile solid-phase synthesis of Baylis–Hillman products from polymeric selenium reagents

Treatment of lithio derivatives of polystyrene-supported methyl α-selenopropionate, 2-selenopropiophenone, 1-selenoethyl phenyl sulfone and diethyl 1-selenoethylphosphonate with aldehydes respectively, followed by cleavage from the polymer by oxidation-elimination with 30% hydrogen peroxide efficiently afforded Baylis–Hillman products in good yields and high purities.

A Novel Liquid-Phase Synthesis of Baylis-Hillman Products Using PEG-Supported α-Phenylselenopropionate Ester

Treatment of the lithio derivative of novel PEG-supported α-phenylselenopropionate ester with aldehydes and subsequent cleavage from the PEG support by oxidative elimination with 30% hydrogen peroxide efficiently afforded Baylis-Hillman products in good yields and high purities.