Enantioselective aldol reaction mediated by chiral lithium amide bases

Highly enantioselective aldol reaction mediated by chiral lithium amide bases was achieved between some methylketones and aldehydes     

Aggregation studies of complexes containing a chiral lithium amide and n-Butyllithium

A system consisting of a chiral lithium amide and n-BuLi in tol-d(8) solution was investigated with (1)H and (13)C INEPT DOSY, (6)Li and (15)N NMR, and other 2D NMR techniques. A mixed 2:1 trimeric complex was identified as the major species as the stoichiometry approached 1.5 equiv of n-BuLi to 1 equiv of amine compound. (1)H and (13)C INEPT DOSY spectra confirmed this lithium aggregate in the solution. The formula weight of the aggregate, correlated with diffusion coefficients of internal references, indicated the aggregation number of this complex. Plots of log D(rel) vs log FW are linear (r > 0.9900). (6)Li and (15)N NMR titration experiments also corroborated these results. These NMR experiments indicate that this mixed aggregate is the species that is responsible for asymmetric addition of n-BuLi to aldehydes.     

Application of chiral lithium amide bases to the thia-Sommelet dearomatization reaction

Thia-Sommelet dearomatization reactions of benzylsulfonium ylides can create highly congested quaternary centers. Chiral bis-lithium amide bases were shown to effect enantiotopic deprotonation of benzylsulfonium ions, leading to thia-Sommelet rearrangement. The chiral trienes were generated in up to 50% ee.     

Mixed dimer and mixed trimer complexes of nBuLi and a chiral lithium amide

Multinuclear and multidimensional NMR spectroscopy have shown that lithium (S)-N-isopropyl-O-methyl-valinol (1-[6Li]) exists in a mixed 2:1 complex with nBu[6Li], (1-[6Li])2/nBu[6Li], in non-coordinating solvents such as hexane or toluene. A 6Li,1H-HOESY NMR spectrum indicates that the complex is a cyclic trimer with a large distance between the di-coordinated lithium and the carbanion of nBu[6Li]. Such arrangements are present in the solid state as previously reported by Williard and Sun. The exchange of lithium atoms within the trimer is slow at -33 degrees C. The exchange barrier (deltaG++) was determined to be 14.7 kcal x mol(-1) from quantitative 6Li,6Li-EXSY spectra. Addition of diethyl ether results in the formation of mixed dimers of (1-[6Li])/nBu[6Li], tetramers of nBu[6Li], and homodimers (1-[6Li])2. The apparent equilibrium constant of the mixed dimer was determined from the 6Li NMR integrals as K = 7.     

Enantioselective butylation of aliphatic aldehydes by mixed chiral lithium amide/n-BuLi dimers

The enantioselective butylation of aliphatic aldehydes with mixtures of n-butyllithium and chiral lithium amides in a diethyl ether–dimethoxymethane solvent mixture is described. Enantiomeric excesses ranging from 91 to 98.5% were observed for several aliphatic alcohols. The asymmetric butylation of the prochiral aldehydes proceeds much faster by the mixed lithium amide/n-BuLi complexes than by tetrameric n-BuLi.     

Enantioselective alkylation of lactams and lactones via lithium enolate formation using a chiral tetradentate lithium amide in the presence of lithium bromide

Enantioselective alkylation of lactams and lactones can be realized up to 98% ee by deprotonation with a chiral tetradentate lithium amide (4b) in the presence of lithium bromide, and subsequent alkylation with active alkylating agents in non-chelating solvents.     

U-Shaped dimeric liquid crystals derived from phthalic acid

Details of the transitional properties of four homologous series of U-shaped liquid crystal materials, the benzene-1,2-di-(4-carboxyalkoxybenzylidene-4-n-alkylanilines), are presented. The spacers incorporate 3 to 6 methylene units, whilst terminal aliphatic chain lengths are varied from 1 to 12 units. Members of the two homologous series with an odd number of methylene units in the spacer form nematic and smectic phases as a function of terminal chain length. Materials with an even number of methylene units in the spacer are purely smectogenic, and in both series the first two homologues form only smectic B phases. For all four series the higher homologues show the phase sequence SF/I-SC-SA-I. X-ray diffraction studies have shown that these smectic phases are composed of molecules arranged in bilayers.     

Nigramides A-S, dimeric amide alkaloids from the roots of Piper nigrum

[structure: see text] Fifteen novel dimeric amide alkaloids possessing a cyclohexene ring, nigramides A-O (1-15), as well as four novel dimeric amide alkaloids possessing a cyclobutane ring, nigramides P-S (17-20), have been isolated from the roots of Piper nigrum. Their structures were elucidated on the basis of their spectroscopic data. The biosynthestic hypothesis of nigramides A-O (1-15) was proposed by an intermolecular Diels-Alder reaction from the corresponding monomeric amides. On the basis of this biosynthetic hypothesis, the first study of the thermal and Lewis acid mediated Diels-Alder reactions of piperine in different organic solvents and under solventless conditions is also described.     

Computational study of solvation and stereoselectivity in deprotonation of cyclohexene oxide by a chiral lithium amide

A detailed computational investigation of possible activated complexes in the epoxide opening of cyclohexene oxide by a chiral lithium amide is presented. Transition states for the two routes giving (S)- and (R)-alkoxides with and without solvent have been calculated. Geometry optimizations at PM3 and HF/3-21G levels of theory, and single point calculations at B3LYP/6-31+G(d) level have been used. The experimentally obtained stereoselectivity is semi-quantitatively reproduced at all levels except PM3//PM3. The factors found to control the stereoselectivity are solvation and some non-bonded interactions other than those previously proposed.     

Solution structures of the mixed aggregates derived from lithium acetylides and a camphor-derived amino alkoxide

Low-temperature (6)Li, (13)C, and (15)N NMR spectroscopies reveal that mixtures of lithium cyclopropylacetylide or lithium phenylacetylide (RCCLi) and a vicinal amino alkoxide derived from camphor (R*OLi) in THF/pentane afford an asymmetric (RCCLi)(3)(R*OLi) mixed tetramer and a C(2)-symmetric (RCCLi)(2)(R*OLi)(2) mixed tetramer depending on the stoichiometries. The corresponding (RCCLi)(R*OLi)(3) mixed tetramer is not observed. R*OLi-mediated additions of PhCCLi to benzaldehyde proceed with up to an 8:1 enantiomeric ratio that depend on both the choice of R*OLi and the PhCCLi/R*OLi stoichiometries. The results are considered in light of a previously proposed mechanism for the 1,2-addition to a trifluoromethyl ketone.     

Composition of the activated complex in the stereoselective deprotonation of cyclohexene oxide by a chiral lithium amide

Chiral lithium amides are being developed for stereoselective synthesis of chiral allylic alcohols in high yields and with high enantiomeric excess. However, rational design of the amides for improved stereoselectivity by computational methods, for example, has not been possible due to lack of knowledge of the activated complexes involved in the reactions. Kinetic results are presented for the stereoselective deprotonation by lithium (S)-1-(2-pyrrolidinylmethyl)pyrrolidide (1-Li) of cyclohexene oxide 2, in diethyl ether (DEE), to form (S)-2-cyclohexen-1-ol (S)-3 in high enantiomeric excess. The results show that the rate limiting activated complex is composed of one lithium amide monomer and one molecule of 2 and presumably a solvent molecule. The diamine 1 is found to catalyze the deprotonation.     

Photoluminescent chiral carbon dots derived from glutamine

The integration of luminescence and chirality in carbon dots (CDs) encourages candidates to explore novel functions and applications of CDs, however, the preparation of chiral CDs is very limited. Herein, we report a hydrothermal method to fabricate chiral CDs by utilizing amino acid enantiomers as the precursors. LGln-CDs or DGln-CDs with uniform size of 3–4 nm show excitation-dependent blue fluorescence in solutions. Circular dichroism measurement confirms the opposite optical rotation of chiral CDs in the region from 200 nm to 300 nm, and the signals can be regulated by concentrations of CDs solution. Time-dependent density functional calculation reveals that polypeptides may exist on the surface of CDs due to the polycondensation of L/DGln at high temperature, and the optical activity of CDs originates from the stacking of neighboring carbonyl groups. The facile synthetic methodology proposed will provide potential opportunities for the preparation and application of chiral and chiroptical CDs-based materials.     

Novel chiral dithioethers derived from l-tartaric acid

The synthesis of a new family of systematically modified chiral dithioethers to be used as ligands is described. Phenylthioether derivative 5 and fluorine-containing dithioether ligands 6–8 and 13–15 were prepared by direct reaction of phenylthiol and o-, m- or p-fluorophenylthiol with two different ditriflate derivatives based on the l-tartaric skeleton. The chiral ditriflate 12 containing a dioxolane moiety was reacted with ethane- and propanedithiol, producing cyclic dithioethers 16 and 17, respectively, in good yields (≈50%). The analogous ditriflate 4 with benzyl ether protecting groups, having a skeleton without restricted rotation, gave the thiolane 9 as the main product.     

Hydrogen release from mixtures of lithium borohydride and lithium amide: a phase diagram study

We recently reported the synthesis of a new quaternary hydride in the lithium-boron-nitrogen-hydrogen quaternary phase diagram with the approximate composition LiB0.33N0.67H2.67 having a theoretical hydrogen content of 11.9 wt %. This new compound forms by the reaction of appropriate amounts of lithium amide (LiNH2) and lithium borohydride (LiBH4) and releases greater than 10 wt % hydrogen when heated. A small amount of ammonia, 2-3 mol % of the generated gas, is also released. We now report a study of hydrogen and ammonia release from the series of reactant mixtures (LiNH2)x(LiBH4)1-x, where x=0.667 corresponds to the composition LiB0.33N0.67H2.67. We measured hydrogen and ammonia release amounts as a function of composition and found that maximum hydrogen and minimum ammonia release do occur for x=0.667. We also present evidence for an additional new quaternary phase and for two possibly metastable phases in this system.     

Preparation of proline derived lithium amide bases and their use in enantioselective deprotonation of meso epoxides

An alternative method of preparation for a range of proline derived chiral lithium amide bases is described. (S)-2-(Pyrrolidinomethyl) pyrrolidine, prepared by the new route, has been used to deprotonate cis and trans ^tbutyldimethylsiloxy-3,4-epoxycyclopentane enantioselectively, thus generating chiral cis and trans ^tbutyldimethylsiloxy-2-cyclopenten-4-ols. The products had higher enantiomeric purity than those produced when the base was prepared by a previously reported method.     

Asymmetric synthesis of the erythrinan alkaloid system using a chiral lithium amide base desymmetrisation as the key step

A new asymmetric approach to the erythrinan alkaloid system is described, which involves chiral base desymmetrisation of a ring fused imide and a 6-exo-trig radical cyclisation as the key steps.