Reaction of some heterocyclic ketones with lithium dimethyl copper

Reaction of lithium dimethyl copper with several heterocyclic ketones results in a 1,4-addition and introduction of a methyl group on the heterocyclic ring. In some cases, addition to the carbonyl also occurs.     

Reversible enolization of beta-amino carboxamides by lithium hexamethyldisilazide

The enolization of beta-amino carboxamides by lithium hexamethyldisilazide (LiHMDS) in THF/toluene and subsequent diastereoselective alkylation with CH(3)I are reported. In situ IR spectroscopic studies reveal that beta-amino carboxamides coordinate to LiHMDS at -78 degrees C before enolization. Comparison with structurally similar carboxamides suggests that the beta-amino group promotes the enolization. IR spectroscopic studies also show that the enolization is reversible. Efficient trapping of the enolate by CH(3)I affords full conversion to products. (6)Li and (15)N NMR spectroscopic studies reveal that lithium enolate-LiHMDS mixed dimers and trimers as well as a homoaggregated enolate are formed during the reaction. At ambient temperature, racemization of the beta-position through a putative reversible Michael addition was observed.     

Stereoselective 1,2-additions of alpha-alkoxymethyllithiums to aldehydes

[reaction: see text]. A chiral derivative of tributylstannylmethanol, readily prepared from L-valine, undergoes Sn-Li exchange to provide an alpha-alkoxyorganolithium that adds to aldehydes with up to 91:9 dr. The diastereoselectivity depends on the solvent and alkyllithium used for transmetalation. Treatment of adducts with acid allowed recovery of the chiral auxiliary and diol with complete stereochemical integrity.     

Lithiation at the 6-position of uridine with lithium hexamethyldisilazide: crucial role of temporary silylation

Lithium hexamethyldisilazide (LiHMDS) can mediate silylation at the 6-position of uridine, although LiHMDS alone is not able to generate the C-6-lithiated uridine. Experimental results showed that temporary silylation of O-4 (or N-3) of the uracil ring triggers the C-6 lithiation with LiHMDS. This finding allowed us to develop an efficient intramolecular alkylation of 5'-deoxy-5'-iodouridine to furnish 6,5'-C-cyclouridine. [reaction--see text]     

Highly enantioselective 1,2-additions of various organolithium reagents to aldehydes

Several asymmetric 1,2-additions of various organolithium reagents (methyllithium, n-butyllithium, phenyllithium, lithioacetonitrile, lithium n-propylacetylide, lithium phenylacetylide) to aldehydes are shown to result in decent to excellent enantiomeric excesses (65–98%) when performed in the presence of a chiral lithium amido sulfide. The chiral lithium amido sulfides invariably exhibited higher levels of enantioselectivity in all the reactions tested, compared to the structurally similar chiral lithium amido ethers and the chiral lithium amide without a chelating group.     

Structural and rate studies of the 1,2-additions of lithium phenylacetylide to lithiated quinazolinones: influence of mixed aggregates on the reaction mechanism

The 1,2-addition of lithium phenylacetylide (PhCCLi) to quinazolinones was investigated using a combination of structural and rate studies. (6)Li, (13)C, and (19)F NMR spectroscopies show that deprotonation of quinazolinones and phenylacetylene in THF/pentane solutions with lithium hexamethyldisilazide affords a mixture of lithium quinazolinide/PhCCLi mixed dimer and mixed tetramer along with PhCCLi dimer. Although the mixed tetramer dominates at high mixed aggregate concentrations and low temperatures used for the structural studies, the mixed dimer is the dominant form at the low total mixed aggregate concentrations, high THF concentrations, and ambient temperatures used to investigate the 1,2-addition. Monitoring the reaction rates using (19)F NMR spectroscopy revealed a first-order dependence on mixed dimer, a zeroth-order dependence on THF, and a half-order dependence on the PhCCLi concentration. The rate law is consistent with the addition of a disolvated PhCCLi monomer to the mixed dimer. Investigation of the 1,2-addition of PhCCLi to an O-protected quinazolinone implicates reaction via trisolvated PhCCLi monomers.     

Reaction of cyclic ketones with KOH-DMSO

Upon reaction of cycloalkanones with a KOH-DMSO system 2-methylenecycloal-kanols are formed, the yield (10–37%) of which decreases in the series: cyclohexanone > cycloheptanone > cyclooctanone > cyclododecanone.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1601–1605, July, 1990.     

Reaction of perfluoro ketones with hexamethyldisilazane

Conclusions Perfluoro ketones react with hexamethyldisilazane under mild conditions to give 2-trimethylsilyloxy-2-trtmethylsilylaminoperfluoropropanes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2352–2353, October, 1972.     

Reaction of ethynyl ketones with o-phenylenediamine

2,4-Diaryl-3H-benzo-1,5-diazepines were obtained by reaction of ethynyl ketones with o-phenylenediamine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1421–1422, October, 1973.     

Reaction of difluoronitroacetyl fluoride with ketones

Conclusions A method was developed for the preparation of -diketones that contain the CF₂NO₂ grouping.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2350–2351, October, 1973.     

Ketone enolization by lithium hexamethyldisilazide: structural and rate studies of the accelerating effects of trialkylamines

Mechanistic studies of the enolization of 2-methylcyclohexanone mediated by lithium hexamethyldisilazide (LiHMDS; TMS2NLi) in toluene and toluene/amine mixtures are described. NMR spectroscopic studies of LiHMDS/ketone mixtures in toluene reveal the ketone-complexed cyclic dimer (TMS2NLi)2(ketone). Rate studies using in situ IR spectroscopy show the enolization proceeds via a dimer-based transition structure, [(TMS2NLi)2(ketone)]++. NMR spectroscopic studies of LiHMDS/ketone mixtures in the presence of relatively unhindered trialkylamines such as Me2NEt reveal the quantitative formation of cyclic dimers of general structure (TMS2NLi)2(R3N)(ketone). Rate studies trace a >200-fold rate acceleration to a dimer-based transition structure, [(TMS2NLi)2(R3N)(ketone)]++. Amines of intermediate steric demand, such as Et3N, are characterized by recalcitrant solvation, saturation kinetics, and exceptional (>3000-fold) accelerations traced to the aforementioned dimer-based pathway. Amines of high steric demand, such as i-Pr2NEt, do not observably solvate (TMS2NLi)2(ketone) but mediate enolization via [(TMS2NLi)2(R3N)(ketone)]++ with muted accelerations. The most highly hindered amines, such as i-Bu3N, do not influence the LiHMDS structure or the enolization rate. Overall, surprisingly complex dependencies of the enolization rates on the structures and concentrations of the amines derive from unexpectedly simple steric effects. The consequences of aggregation, mixed aggregation, and substrate-base precomplexation are discussed.     

Density functional study of lithium hexamethyldisilazide (LiHMDS) complexes: effects of solvation and aggregation

The title compound, lithium hexamethyldisilazide (LiHMDS), has been studied using modern quantum-chemical methods in the form of the B3LYP approach. Monomers, dimers, trimers, and tetramers, microsolvated with up to four THF molecules have been considered. The choice of model complex is seen to be important-for instance, the simpler water molecule is shown to be an inappropriate substitute for the THF solvent. Calculated lithium NMR shieldings are reported, but by themselves, they seem to be insufficient for unequivocal assignments of the different species. The energetics of aggregation and solvation have been studied. Temperature effects are seen to be important, and the degrees of solvation and aggregation are higher at 0 K than at 298 K. The highest degree of THF solvation for the monomer and dimer is found to be three (0 K) and two (298 K), respectively. The highest possible degree of aggregation for unsolvated LiHMDS is four. However, in nonpolar solvents, formation of the LiHDMS dimer from the trimer is thermodynamically preferred. The pathway is likely to involve an intermediate tetramer. In THF solution, di-solvated monomers and dimers are the most likely species.     

Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.     

Chiral N-phosphonyl imine chemistry: asymmetric 1,2-additions of allylmagnesium bromides

Chiral N-phosphonyl homoallylic amines were synthesized by the reaction of allylmagnesium bromide with chiral N-phosphonyl imines. The C₂-symmetric chiral N-phosphonyl group was optimized for this reaction. Excellent yields and good diastereoselectivities were obtained for eight examples.     

Novel reduction of perfluoroalkyl ketones with lithium alkoxides

The reaction of tert-butyl N-(2-bromophenyl)carbamate (1) with ethyl perfluorooctanoate in the presence of tert-butyllithium did not give the desired N-(2-perfluorooctanoylphenyl)carbamate (3) but gave 1-hydroxy-1H-perfluorooctyl compound (4), which was supposed to be formed by the reduction of 3. A similar reaction of 2,2,2-trifluoroacetophenone with tert-butyllithium did not gave any reduction product. Detailed investigation showed that lithium ethoxide worked as the reducing agent of this abnormal reduction. By the reaction of lithium isopropoxide, an aldol product from 2,2,2-trifluoroacetophenone with acetone was isolated, while perfluoroheptyl or perfluoropropyl phenyl ketones were reduced by this alkoxide in a high yield without formation of the aldol adduct.