Teruko Tsuchida

Asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides catalyzed by chiral binaphthyldiimine-Ni(II) complexes.

Asymmetric cycloaddition reactions between several nitrile oxides and 3-(2-alkenoyl)-2-oxazolidinones and 2-(2-alkenoyl)-3-pyrazolidinone derivatives were carried out in the presence of chiral binaphthyldiimine (BINIM)-Ni(II) complexes as catalysts. Using (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (30 mol %), good regioselectivity (4-Me/5-Me = 85:15) along with high enantioselectivity (96% ee) of the 4-Me adduct were obtained for the reaction between isolable 2,4,6-trimethylbenzonitrile oxide and 3-crotonoyl-5,5-dimethyl-2-oxazolidinone. Substituted and unsubstituted benzonitrile oxides and aliphatic nitrile oxides, which were generated from the corresponding hydroximoyl chloride in the presence of MS 4A, were reacted with 3-crotonoyl-5,5-dimethyl-2-oxazolidinone, 5,5-dimethyl-3-(2-pentenoyl)-2-oxazolidinone, 5,5-dimethy-3-[3-(ethoxycarbonyl)propenoyl]-2-oxazolidinone, 1-benzyl-2-crotonoyl-5,5-dimethyl-3-pyrazolidinone, and 1-benzyl-2-[3-(ethoxycarbonyl)propenoyl]-5,5-dimethy-3-pyrazolidinone in the presence of (R)-BINIM-4Ph-2QN-Ni(II) or (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complexes (10-30 mol %) as catalysts to give the corresponding cycloadducts in high yields, with high regioselectively (4-R/5-R = 85:15-99:1) and with moderate to high enantioselectivities (42-95% ee) of the 4-R adducts. Higher enantioselectivities and regioselectivities were obtained for the reactions using pyrazolidinone derivatives as the dipolarophiles. For the cycloadditions of 2-(2-alkenoyl)-1-benzyl-5,5-dimethyl-3-pyrazolidinones catalyzed by (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (30 mol %), the enantioselectivity varied from 75% to 95% ee. The reactions between several nitrile oxides and 2-acryloyl-1-benzyl-5,5-dimethyl-3-pyrazolidinone in the presence of (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (10 mol %) resulted in enantioselectivities (79-91% ee) that exceed those of previously reported enantioselective cycloadditions of acrylic acid derivatives. Furthermore, studies using a molecular modeling program using PM3 calculations were carried out to gain insight into the mechanisms of the asymmetric induction.

Asymmetric cycloaddition reactions of diazoesters with 2-alkenoic acid derivatives catalyzed by binaphthyldiimine-Ni(II) complexes.

The catalytic activity of chiral binaphthyldiimine (BINIM)-Ni(II) complexes for asymmetric enantioselective diazoalkane cycloadditions of ethyl diazoacetate with 3-acryloyl-2-oxazolidinone and 2-(2-alkenoyl)-3-pyrazolidinone derivatives was evaluated. The cycloadditions of 3-acryloyl-2-oxazolidinone and its 5,5-dimethyl derivative, in the presence of the BINIM-Ni(II) complex (10 mol %; prepared from (R)-BINIM-4Ph-2QN (ligand C) and Ni(ClO(4))(2)·6H(2)O) afforded 2-pyrazolines having a methine carbon substituted with an oxazolidinonyl group in moderate ratios (70:30 to 72:28), along with high enantioselectivities (90-92% ee) via 1,3-proton migration. On the basis of the investigations on the counteranions of the Ni(II) complex, the N-substituent of pyrazolidinone, and reaction temperatures, the optimal enantioselectivity (97% ee) and ratio (85:15) of 2-pyrazoline were obtained for the reaction of 2-acryloyl-1-benzyl-5,5-dimethyl-3-pyrazolidinone in the presence of (R)-BINIM-4Ph-2QN-Ni(II) ((R)-C/Ni(II)) complex prepared using Ni(BF(4))(2)·6H(2)O. In the cases of 1-benzyl-2-crotonoyl-5,5-dimethyl-3-pyrazolidinone, 1-benzyl-2-(2-butenoyl)-5,5-dimethyl-3-pyrazolidinone, and 1-benzyl-5,5-dimethyl-2-(3-ethoxycarbonyl)propenoyl-3-pyrazolidinone, the use of the (R)-BINIM-2QN-Ni(II) ((R)-A/Ni(II)) complex gave good to high enantioselectivities (85-93% ee) with the sole formation of the 2-pyrazoline having a methine carbon substituted with a pyrazolidinonyl group. Relatively good enantioselectivity (77% ee) was observed for the reaction between 2-acryloyl-5,5-dimethyl-1-naphthylmethyl-3-pyrazolidinone and an α-substituted diazo ester, ethyl 2-diazo-3-phenylpropanoate, which has yet to be employed as a diazo substrate in asymmetric cycloaddition reactions catalyzed by a chiral Lewis acid.

Stabilization of singlet ethoxycarbonylnitrene by 1,4-dioxan. Part 4. Yield of nitrene products in 1,4-dioxan–cyclohexane and effect of cyclohexane-1,2-dione on C–H insertion

A study of the yield of ethoxycarbonylnitrene products for the thermolysis and photolysis of ethyl azidoformate in 1,4-dioxan–cyclohexane shows that the singlet state of the nitrene is stabilized by 1,4-dioxan. The results for the effect of added cyclohexane-1,2-dione both on the yield and on the selectivity for the insertion of nitrene suggest that the dione predominantly traps the triplet rather than the singlet nitrene to give 3-ethoxycarbonylimino-2-hydroxycyclohexanone, and that a complex which can react with the C–H bonds of cyclohexane is formed by inter-action of 1,4-dioxan with the singlet, not the triplet nitrene.

Stabilization of singlet ethoxycarbonylnitrene by 1,4-dioxan. Part 2. Selectivity for insertion into C–H bonds

The selectivity for insertion of ethoxycarbonylnitrene generated thermally or photochemically from ethyl azidoformate into the tertiary, secondary, and primary C–H bonds of iso-octane, cyclohexane, and n-octane were determined at various concentrations of 1,4-dioxan. The relative selectivity for secondary and primary C–H bonds is almost independent of the 1,4-dioxan concentration, whereas that for tertiary and primary C–H bonds decreases with an increase in the quantity of 1,4-dioxan. The tendency for this decrease is greater in photolysis than thermolysis. The results are explained in terms of steric hindrance in the transition state of the reaction between the crowded tertiary C–H bonds and a nitrene–1,4-dioxan complex. The variation of the selectivity with temperature supports formation of this complex.

Perturbation of rearrangement courses by cyclohepta-amylose

Dibenzylmethylsulphonium fluoroborate (I), when treated with aqueous sodium hydroxide in the presence of cyclohepta-amylose, prefers the Sommelet over the Stevens rearrangement by the formation of an inclusion complex, while rate measurements reveal that cyclohepta-amylose retards slightly the rearrangement reactions.

Oligomerization of acrylic acid derivatives by a reaction with the alkylcopper(I)-phosphine complex

Reaction of alkylcopper(I)phosphine complexes with electron-deficient olefins affected preferentially the products based on oligomerization, e.g. the product obtained by sequential conjugated addition, trimerization and cyclization from methyl methacrylate and the dimerization product from butyl acrylate.

Stabilization of singlet ethoxycarbonylnitrene by 1,4-dioxan. Part 3. Stereospecificity for the addition to 4-methylpent-2-ene of the nitrene generated from ethyl azidoformate

The addition to cis-4-methylpent-2-ene of ethoxycarbonylnitrene generated by the photolysis of ethyl azidoformate was carried out in 1,4-dioxan–cyclohexane. Both the stereospecificity of addition and the sum of all singlet nitrene products increase with an increase in the concentration of 1,4-dioxan. The relative yield of cis- to trans-aziridine is proportional to the concentration of 1,4-dioxan, and the total triplet nitrene products stay practically constant. This suggests that increased concentration of the singlet state by 1,4-dioxan corresponds to increased concentration of a singlet 1,4-dioxan–nitrene complex, not the free singlet nitrene. For addition using trans-4-methylpent-2-ene in place of the cis-isomer, there was a smaller increase in the stereospecificity induced by 1,4-dioxan. On the other hand, for addition of the nitrene generated by thermolysis, the stereospecificity was almost independent of the concentration of 1,4-dioxan.

Stabilization of singlet ethoxycarbonylnitrene. Effect of dichloromethane on insertion into tetrahydrofuran and cyclohexane

Ratios of singlet ethoxycarbonylnitrene to total nitrene species for the insertion of the nitrene into tetrahydrofuran and cyclohexane in dichloromethane were determined by taking into consideration tetrahydrofuran–dichloromethane interactions, solvent polarity effects, and triplet quenching experiments. In the case of the nitrene generated photochemically, the rations were almost independent of dichloromethane concentration. This probably suggests that singlet destabilization by the external heavy atom effect of dichloromethane is counterbalanced by singlet stabilization due to an interaction between the nitrene and the lone pair electrons of dichloromethane. Whereas the result for the insertion of the nitrene generated thermally reveals slightly predominant singlet destabilization compared with the photochemical case. This may also result from different temperature conditions.

Stabilization of singlet ethoxycarbonylnitrene by 1,4-dioxan

A study of the solvent polarity and triplet quenching effects on the insertion of ethoxycarbonylnitrene into cyclic ethers demonstrates that the singlet state of the nitrene is stablized by 1,4-dioxan. The lowering of the yield of the triplet nitrene product compared with that of the singlet nitrene product in 1,4-dioxan as solvent supports this postulate. The activation parameters for insertion in the presence and absence of a triplet quencher further support singlet stabilization. This is discussed in the terms of the interaction of the nitrene p orbital with the lone pair electrons of ether oxygen atoms.