Excited-state palladium-catalysed reductive alkylation of imines: scope and mechanism

Palladium catalysis induced by visible-light irradiation is a promising tool for promoting unusual chemical transformations. We describe the development of excited-state palladium-catalyzed reductive alkylation of imines with alkyl bromides. The new methodology shows broad functional group tolerance and can additionally be applied in the direct three-component reaction of aldehydes, anilines, and alkyl bromides to give the alkyl amines under mild reaction conditions. Time-resolved photoluminescence experiments allowed the determination of the excited-state reaction kinetics and indicate that the reaction is proceeding via the inner-sphere electron transfer mechanism.

Palladium catalysis induced by visible-light irradiation is a promising tool for promoting unusual chemical reactivity. Here, the hybrid alkyl radical/Pd(i) species generated is used to promote the reductive alkylation of imines.     

Chemo- and regioselectivity-tunable Pd-catalyzed allylic alkylation of imines

α-Carbanions of cyclic and acyclic imines have been successfully applied as nucleophiles in the Pd-catalyzed allylic alkylation reaction. Tuning of chemo- and regioselectivity has been realized by using t-BuOK/THF and LDA/toluene to give branched and linear products, respectively, with high regio- and diastereoselectivities. A plausible mechanism is proposed on the basis of the experimental results and DFT calculations.     

Lithium 2,2,6,6-tetramethylpiperidide-mediated alpha- and beta-lithiations of epoxides: solvent-dependent mechanisms

Lithium 2,2,6,6-tetramethylpiperidide (LiTMP)-mediated alpha- and beta-lithiations of epoxides are described. LiTMP displays a markedly higher reactivity than does lithium diisopropylamide, consistent with literature reports. Detailed rate studies of LiTMP/THF and LiTMP/Me(2)NEt mixtures reveal similar rates but significant mechanistic differences. LiTMP-mediated alpha-lithiation of cis-cyclooctene oxide with subsequent oxacarbenoid formation and transannular C-H insertion proceeds via monosolvated dimers in both THF and Me(2)NEt. LiTMP-mediated beta-lithiation of 2,3-dimethyl-2-butene oxide affords the corresponding allylic alcohol via a monosolvated monomer in THF and a monosolvated dimer in Me(2)NEt. We discuss how the solvent-dependent aggregation of LiTMP markedly influences the rate profile. The reaction transition structures are examined with density functional computations.     

The Pd-catalysed asymmetric allylic alkylation reactions of sulfamidate imines

The Pd-catalysed asymmetric allylic alkylation (Pd-AAA) of prochiral enamide anions derived from 5H-oxathiazole 2,2-dioxides has been developed. Various 4,5-disubstituted and 4-substituted cyclic sulfamidate imines have participated in the transformation with a range of allyl carbonates—as well as 2-vinyl oxirane, 2-vinyl-N-tosylaziridine, and 2-vinyl-1,1-cyclopropane dicarboxylate—to furnish the desired C-allylated products in moderate to high yields, with high regioselectivites and generally high enantioselectivities. Conversion between N- and C-allyl products was observed, with the N-allylated products converting to the C-allylated products over time. The resulting high-value allylated heterocyclic products all bear a tetrasubstituted stereogenic centre and can be reduced to an allylated chiral sulfamidate or an amino alcohol.

The Pd-catalysed asymmetric allylic alkylation (Pd-AAA) of prochiral enamide anions derived from 5H-oxathiazole 2,2-dioxides has been developed.     

Indium-copper-mediated barbier-grignard-type alkylation reaction of imines in aqueous media

An efficient system of In/CuI/InCl3 was developed for Barbier-Grignard-type alkylation reactions of simple imines, using a one-pot condensation of various aldehydes, amines (including aliphatic and chiral version), and alkyl iodides in water or aqueous media. The reactions proceeded efficiently at room temperature to give the desired products in moderate to good yields. Good diastereoselectivities were obtained when using L-valine methyl ester as substrate.     

Stereoselective alkylation of alpha,beta-unsaturated imines via C-H bond activation

The stereoselective alkylation of alpha,beta-unsaturated imines via C-H activation followed by imine hydrolysis produces tri- and tetrasubstituted alpha,beta-unsaturated aldehydes. In the presence of a rhodium catalyst, alpha,beta-unsaturated N-benzyl imines derived from methacrolein, crotonaldehyde, and tiglic aldehyde undergo directed C-H activation at the beta-position and react with terminal alkenes and alkynes to form the tri- and tetrasubstituted alpha,beta-unsaturated imines with very high stereoselectivity. Hydrolysis to provide alpha,beta-unsaturated aldehydes can be performed under carefully controlled conditions that maintain the stereochemistry of the beta-alkylated imine products. Alternatively, for beta-alkylation products of the N-benzyl imine of methacrolein, hydrolysis can be performed under conditions that provide complete isomerization to the E isomer.     

Enantioselective synthesis of ring-C aromatic steroids by asymmetric Michael-type alkylation of chiral imines.

Optically active phenanthrones 7 and 12 were prepared, using the asymmetric process involving Michael-type alkylation of chiral imines. Compound 12 was then transformed into the ring-C aromatic steroid 16.     

Quinolyl-functionalised Cp-chromium polymerisation catalysts: synthesis and crystal structures of alkylation products

The quinolyl-functionalised Cp-chromium(III) complexes 1 and 2, which serve as precursors for highly active olefin polymerisation catalysts, were alkylated with benzylmagnesium chloride. From these reactions, the new metal complexes 4, 5 and 6 were obtained and structurally characterised. The expected alkylchromium compound 4 is formed together with complex 5, where the nucleophile replaced a hydrogen atom at the quinoline substituent. The dinuclear complex 6 is formed by nucleophile addition, rearrangement and dimerisation.     

Indium-silver- and zinc-silver-mediated barbier-grignard-type alkylation reactions of imines by using unactivated alkyl halides in aqueous media

In the presence of In or Zn/AgI/InCl(3), an efficient and practical method for the Barbier-Grignard-type alkylation reactions of simple imines by using a one-pot condensation of various aldehydes, amines (including the aliphatic and chiral version), and secondary alkyl iodides has been developed. The reaction proceeded more efficiently in water than in organic solvents. Without the use of CuI, it mainly gave the imine self-reductive coupling product, which was not the alkylated product. Good diastereoselectivities (up to 92:8 dr) were obtained when L-valine methyl ester was used as the substrate.     

Highly enantioselective synthesis of 3,3-disubstituted 4-piperidones by michael alkylation of chiral piperidone imines

A method for the highly enantioselective synthesis of (3S)- and (3R)-3,3-disubstituted 4-piperidones with an optical purity of 98% based on the deracemizing alkylation of 3-substituted 4-piperidones during Michael addition of their chiral imines to electrophilic alkenes was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1072–1078, August, 1992.     

Nitrile imines: matrix isolation, IR spectra, structures, and rearrangement to carbodiimides

The structures and reactivities of nitrile imines are subjects of continuing debate. Several nitrile imines were generated photochemically or thermally and investigated by IR spectroscopy in Ar matrices at cryogenic temperatures (Ph-CNN-H 6, Ph-CNN-CH(3)17, Ph-CNN-SiMe(3)23, Ph-CNN-Ph 29, Ph(3)C-CNN-CPh(3)34, and the boryl-CNN-boryl derivative 39). The effect of substituents on the structures and IR absorptions of nitrile imines was investigated computationally at the B3LYP/6-31G* level. IR spectra were analyzed in terms of calculated anharmonic vibrational spectra and were generally in very good agreement with the calculated spectra. Infrared spectra were found to reflect the structures of nitrile imines accurately. Nitrile imines with IR absorptions above 2200 cm(-1) have essentially propargylic structures, possessing a CN triple bond (typically PhCNNSiMe(3)23, PhCNNPh 29, and boryl-CNN-boryl 39). Nitrile imines with IR absorptions below ca. 2200 cm(-1) are more likely to be allenic (e.g., HCNNH 1, PhCNNH 6, HCNNPh 43, PhCNNCH(3)17, and Ph(3)C-CNN-CPh(3)34). All nitrile imines isomerize to the corresponding carbodiimides both thermally and photochemically. Monosubstituted carbodiimides isomerize thermally to the corresponding cyanamides (e.g., Ph-N═C═N-H 5 → Ph-NH-CN 8), which are therefore the thermal end products for nitrile imines of the types RCNNH and HCNNR. This tautomerization is reversible under flash vacuum thermolysis conditions.     

On the sites and mechanisms of alkylation in the nucleic acids

The intrinsic capacity (computed by ab initio molecular orbital techniques) of ethyl and methyl cations to bind to the anionic oxygens of the phosphate groups of the nucleic acids is found to be larger than their affinity for the carbonyl oxygens or for the nitrogens of the bases cytosine and guanine. Analysis of the components of the binding energies indicates that the preference of the ethyl cation for the oxygens of the phosphate or for those of the bases is due to different reasons. The results are discussed in connection with the available experimental observations.     

Particle interactions in kaolinite suspensions and corresponding aggregate structures

The surface charge densities of the silica face surface and the alumina face surface of kaolinite particles, recently determined from surface force measurements using atomic force microscopy, show a distinct dependence on the pH of the system. The silica face was found to be negatively charged at pH>4, whereas the alumina face surface was found to be positively charged at pH<6, and negatively charged at pH>8. The surface charge densities of the silica face and the alumina face were utilized in this study to determine the interaction energies between different surfaces of kaolinite particles. Results indicate that the silica face-alumina face interaction is dominant for kaolinite particle aggregation at low pH. This face-face association increases the stacking of kaolinite layers, and thereby promotes the edge-face (edge-silica face and edge-alumina face) and face-face (silica face-alumina face) associations with increasing pH, and hence the maximum shear-yield stress at pH 5-5.5. With further increase in pH, the face-face and edge-face association decreases due to increasing surface charge density on the silica face and the edge surfaces, and decreasing surface charge density on the alumina face. At high pH, all kaolinite surfaces become negatively charged, kaolinite particles are dispersed, and the suspension is stabilized. The face-face association at low pH has been confirmed from cryo-SEM images of kaolinite aggregates taken from suspension which show that the particles are mostly organized in a face-face and edge-face manner. At higher pH conditions, the cryo-SEM images of the kaolinite aggregates reveal a lower degree of consolidation and the edge-edge association is evident.     

Nucleophilic metal complexes as acylation catalysts: solvent-dependent "switch" mechanisms leading to the first catalyzed Staudinger reaction

[formula: see text] Catalytic acylation using complex transition metal salts MCo(CO)4 is demonstrated. Surprisingly, a solvent-dependent mechanistic "switch" results in a Lewis acid-based acylation mechanism in nonpolar media and a nucleophilic mechanism in polar organic media. These observations lead to the first example of a catalyzed Staudinger reaction to form beta-lactams.     

N-(甘氨酸薄荷酯)-(+)-樟脑亚胺在烷基化反应中的双手性诱导效应

本文报道了从(+)-樟脑与(+)或(-)-甘氨酸薄荷醇酯所得的亚胺的烷基化反应, 烷基化产物经水解得到(R)-氨基酸。与N-(特丁氧羰基亚甲基)-(+)-樟脑亚胺相比,由于存在匹配的双手性诱导效应, 而使N-[甘氨酸-(+)-薄荷酯]-(+)-樟脑亚胺烷基化的立体选择性有明显的提高(43.8-98%),而不匹配的N-[甘氨酸-(-)-薄荷醇酯]-(+)-樟脑亚胺烷基化的立体选择性明显降低。它们的甲基化都给出(S)-丙氨酸, 且立体选择性不受薄荷酯的构型影响。     

Effect of solvent quality on aggregate structures of common surfactants

Aggregate structures of two model surfactants, AOT and C12E5 are studied in pure solvents D2O, dioxane-d8 (d-diox) and cyclohexane-d12 (C6D12) as well as in formulated D2O/d-diox and d-diox/C6D12 mixtures. As such these solvents and mixtures span a wide and continuous range of polarities. Small-angle neutron scattering (SANS) has been employed to follow an evolution of the preferred aggregate curvature, from normal micelles in high polarity solvents, through to reversed micelles in low polarity media. SANS has also been used to elucidate the micellar size, shape as well as to highlight intermicellar interactions. The results shed new light on the nature of aggregation structures in intermediate polarity solvents, and point to a region of solvent quality (as characterized by Hildebrand Solubility Parameter, Snyder polarity parameter or dielectric constant) in which aggregation is not favored. Finally these observed trends in aggregation as a function of solvent quality are successfully used to predict the self-assembly behavior of C12E5 in a different solvent, hexane-d14 (C6D14).