This chapter presents the study of P1/P2 chiral main chain polymers for the Zn(II) cascade and the chiral recognition of (R)-1-phenyl-N-[(pyridin-2-yl)methylene/methyl]ethanamine and (S) -1-phenyl-N-[(pyridin-2-yl)methylene/methyl]ethanamine (Scheme 5). 5 Chiral polymers for the fluorometric recognition of optically active 1-phenyl-N-[(pyridin-2-yl)methylene/methyl]ethanamines.
Synthesis of Chiral Main Chain Polymers Bonded with (R,R)- Salen and 1,4-Dioctyloxybenzene as Alternate Segments
Introduction
After the reaction is complete, the catalyst can be separated by solvent or thermal precipitation, membrane filtration, or size exclusion chromatography. Complexes containing these ligands are also soluble in many common organic solvents and can be separated from the products by precipitation, membrane, or nanofiltration techniques.
Chiral Main Chain Polymers with (R,R)-Salen
Following the success of main-chain cross-linked chiral polymer catalysts, Zheng et al. As the degree of crosslinking increased, it became more difficult for the catalyst to form oxo bridges between two nearby metal centers, resulting in lower levels of enantioselectivity.
Present Study
- Synthesis of Non-linear Polymers P1-P2
- Synthesis of Linear Polymers P3-P4
The reaction of 1,4-hydroquinone 11 with 1-bromooctane in the presence of K2CO3 gave 1,4-dioctyloxybenzene 12 which could be brominated with Br2 to give 1,4-dibromo-2,5-dioctyloxybenzene 13 in 85% yield liver. 15 The latter 13 was reacted with trimethoxyborane in the presence of n-BuLi followed by acid hydrolysis to give 2,5-dioctyloxyphenyl diboronate 15 in 80% yield (Scheme 13).19. The synthesis of the polymers P3-P4 was then pursued by condensation of 18b with chiral (1R,2R)-diaminocyclohexane 19a and (1R,2R)-diphenylethylenediamine 19b in CHCl3 (Scheme 18).
Chiral Titanium(IV)-Catalyzed Asymmetric 1,2-Addition of TMSCN to Aldehydes
Introduction
The most commonly used alternative source of cyanide is trimethylsilyl cyanide (TMSCN = (CH3)3SiCN).8 The reaction can be induced thermally or by a variety of catalysts, including Lewis acids, bases, and nucleophiles. Since trimethylsilyl cyanide is also a good silylating agent9, it would silylate the initially formed cyanohydrin, leading to the formation of cyanohydrin trimethylsilyl ether and regeneration of hydrogen cyanide.
Synthetic Applications of Chiral Cyanohydrins
Trimethylsilyl cyanide is only the simplest example of a family of silyl cyanides, and there are reports of the addition of other silyl cyanides to carbonyl compounds.10 In general, the other silyl cyanides are less reactive than trimethylsilyl cyanide, but have the advantage of producing cyanohydrins. silyl ethers which are more stable with respect to hydrolysis. With less reactive nucleophiles (DIBALH and Grignard reagents), appropriately protected cyanohydrins undergo a single addition reaction, initially leading to imines, as shown in Scheme 7.11e-f. Subsequent hydrolysis of the imines yields α-hydroxyaldehydes and ketones, while transimination yields imines.
Enzyme Catalysis
The second nucleophilic addition occurs in a stereoselective manner due to the formation of a chelated intermediate and has been used to prepare a series of ephedrine analogues. Cyanohydrins can be converted into sulfonate esters, and the latter undergo SN2 reactions with a series of nucleophiles and with inversion of configuration, as shown in Scheme 8.11i This approach has been used to prepare chiral α-azido-nitriles,11j α-aminonitriles , 11j-k aziridines,11l α-thionitriles11m and α-fluoronitriles11n and to reverse the stereochemistry of cyanohydrins.11i The α-azido nitriles are particularly versatile intermediates for the synthesis of both α-amino acids and 1,2-diamines.11j .
Organocatalysis
The Feng group reported the use of chiral and achiral N-oxides as catalysts for both racemic and asymmetric cyanohydrin synthesis.14n-o Bis-N-oxides 7a,b were found to act as efficient organocatalysts for the asymmetric addition of trimethylsilyl cyanide to aromatic aldehydes14p and the monoacetals of 1,2-diketones (Scheme 5).14q Interestingly, much higher enantioselectivities (85–93% using catalyst 7a) were obtained with the ketone substrates than those of the aldehydes (53–73% using catalyst 7b).
Chiral Metal Catalysts
- Chiral Alkali Metal Catalysts
- Chiral Transition Metal Catalysts
- Chiral Group(III) Metal Catalysts
- Chiral Rare Earth Metal Catalysts
Decreasing the reaction temperature did not result in a significant increase in enantioselectivity (90% enantiomeric excess at -80 °C as opposed to 86% ee at ambient temperature). The authors subsequently reported the use of chiral dimeric Ti(IV)-salen complex 12 for the asymmetric cyanohydrin synthesis (Scheme 8). 1 hour when only 0.1 mol% catalyst was used. Kim and Lee used the chiral Mn(III) salen 14 to catalyze the trimethylsilyl cyanide addition to aromatic and aliphatic aldehydes in 82–96% yield and 44–62% ee (Scheme 10).16i A triphenylphosphine oxide co-catalyst was used for to increase the reaction rate.
A number of different aldehydes were used as substrates and the best result of 62% ee was obtained with p-chlorobenzaldehyde. A similar asymmetric induction can be obtained for both aromatic (electron-rich and electron-deficient) and aliphatic substrates. Kim and Song used chiral Al(III)-salen 16 with triphenylphosphine oxide as an additive for the cyanosilylation of aldehydes (Scheme 12).16k-l A range of aliphatic and aromatic aldehydes were studied with up to 86% ee.
Present Study
After completion, the reaction mixture was concentrated (ca. 0.5 mL) and the resulting solution was treated with MeOH (ca. 0.5 mL). The resulting solution was concentrated in vacuo, and the residue was washed with MeOH (5 mL) to give P1a as a yellow solid (221 mg). The resulting solution was concentrated in vacuo, and the residue was washed with MeOH (5 mL) to give P2a as a yellow solid (217 mg).
The resulting solution was concentrated in vacuo and the residue was washed with MeOH (5 mL) to give P3a as a yellow solid (106 mg). The resulting solution was concentrated in vacuo and the residue was washed with MeOH (5 mL) to give 9a as a yellow solid (108 mg). The progress of the reaction was monitored by TLC using ethyl acetate and hexane as eluent.
Chiral Titanium(IV)-Catalyzed Asymmetric Sulfoxidation with Aqueous Hydrogen Peroxide
Introduction
Oxidation Reactions
- Metal Catalyzed Reactions
- Reactions with Organic Peroxides
- Reactions with Hydrogen Peroxide
- Metal-Free Reactions
- Electrochemical Methods
- Biological Methods
- Kinetic Resolution of Sulfoxides
- Oxidative Methods
A chiral vanadium complex derived from VO(acac)2 and ligands 29-30 studied for the oxidation of sulfides in the presence of aqueous hydrogen peroxide with 90% ee (scheme R,5R)-5-[(hydroperoxydiphenyl)methyl]-2, 2- dimethyl-1,3-dioxolan-4-yl-diphenylmethanol 31 (TADOOH), obtained from hydrogen peroxide and tetraaryl-1,3-dioxolan-4,5-dimethanol (TADDOL), studied for the oxidation of sulfides with 86% ee (Scheme 24).28. In 1976, Firth and Miller reported the electrochemical oxidation of sulfides with limited enantioselectivity. 32a Although the results obtained were poor (3% ee), this was the first report of the electrochemical asymmetric oxidation of sulfides. Cytochrome P450 monooxygenase was cloned from Rhodococcus species ECU0066, which is used for sulfide oxidation with 99% ee (Scheme 30).35.
While asymmetric sulfoxidation is attractive for the preparation of optically active sulfoxides, the kinetic resolution of sulfoxides has also been extensively explored as an alternative method. Most kinetic resolutions involve the preferential oxidation of one enantiomer over the other. Reaction of α-sulfinyl carbanion derived from methyl p-tolyl sulfoxide with optically active menthyl carboxylate gave β-ketosulfoxide with up to 71% ee (Scheme 33).38.
Nucleophilic Substitution
Present Study
With the optimized conditions in hand, the scope of the protocol for other sulfides was explored (Table 3). The formation of the intermediate c may be favored compared to d to minimize the steric repulsion (Scheme 41). The oxidation of the coordinated sulfide in c by oxygen transfer can give the intermediate e that can complete the catalytic cycle.
Drying (Na2SO4) and evaporation of the solvent gave a residue which was further purified on silica gel column chromatography using hexane and EtOAc as eluent. The resulting mixture, after stirring for 3 hours, was used for the catalysis of the oxidation reaction. Drying (Na2SO4) and evaporation of the solvent gave a residue which was purified on silica gel column chromatography using hexane and EtOAc as eluent.
Chiral Main Chain Polymers as OFF-ON Chemosensor for the Fluorometric Detection of Zn 2+
- Introduction
- Diamine Based Schiff’s Bases as Chemosensor for Zn 2+ Detection .1 Small Molecules as Probe for Zn 2+ Detection
- Polymers as Probe for Zn 2+ Detection
- Present Study
- References
A few studies have focused on the use of stereoregular organic polymers for detection of metal ions,4a,19 because the selective coordination and binding of certain metal ions to the chromophoric site of the polymers can greatly affect the optical properties of the polymers. Xu et al synthesized a chiral polymer 6 incorporating an (R,R)-salen moiety by our condensation methodology and showed that the polymer 6 exhibits excellent fluorescent sensor properties for the detection of Zn2+ (Scheme 6).19k ,21 Compared to other cations (Na+, K+, Mg2+, Ca2+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cu2+, Ag+, Cd2+, Hg2+ and Pb2+), Zn2+ can show a pronounced fluorescence enhancement as well as a large blue shift of produces the polymer fluorescence. The polymer P2 with Zn2+ emits a strong blue fluorescence, due to the formation of Zn(II) polymer complex contributing to the non-radiative decay of the excited state of the Zn(II) polymer complex as well as the quenching of the photoinduced -electron transfer (PET) of the lone pair of the electrons of nitrogen.22 Furthermore, a blue shift (~50 nm) was observed in the emitted light which can be caused by reduction in the HOMO energy level of the polymer at the formation of the Zn(II) polymer complex.23 The polymer P2 which gave the best fluorescence enhancement was further studied with varied Zn2+.
In contrast, the addition of metal ions such as Ni2+, Co2+, and Pb2+, and Cu2+, Al3+, Ce3+, and Fe3+ ions to Zn(II) polymer complex solutions led to quenching of Zn(II) complex fluorescence. . However, no change in the fluorescence intensity of the Zn(II) polymer complex was observed. Solutions of polymers P1-P2 (3 mL, 1 x 10-5 M in THF relative to the monomer unit) and metal nitrate salts (100 μL, 3 x 10-4 M in water, 1 equiv) were thoroughly mixed. at ambient temperature to produce the corresponding metal-polymer complexes (Figure 1).
Chiral Recognition of Optically Active 1-Phenyl-N-[(pyridin-2-yl) methylene/methyl]ethanamines
- Introduction
- Chiral Main Chain Polymers for Chiral Recognition
- Chiral Dendrimers for Chiral Recognition
- Chiral Macrocyclic System for Chiral Recognition
- Present Study
- References
This can also be attributed to the lower π-π* band gap of the polymer which may facilitate the photoinduced electron transfer quenching by the amino alcohol. Although this enantioselectivity was small, it was greater than using (R)-BINOL which showed no difference whatsoever in the fluorescence quenching when treated with the two enantiomers of the amino alcohol 2. This interaction inhibited the PET fluorescence quenching of the macrocycle by only pairing electrons on nitrogen atoms, leading to the enhanced fluorescence.
To reveal the effect of chelating the imine, R-22 and S-22 were reduced with NaBH4 to give (R)-1-phenyl-N-[(pyridin-2-yl)methyl]ethanamine R-23 and ( S)-1-phenyl-N-[(pyridin-2-yl)methyl]ethanamine S-23, whose interaction with Zn(II)-polymer P1-P2 complexes was investigated (Figure 11). Evaporation of the solvent gave a residue which was purified on silica gel column chromatography with EtOAc and hexane as eluent to give R-23 as a colorless liquid in 95% (201 mg) yield. Evaporation of the solvent gave a residue which was purified on silica gel column chromatography with EtOAc and hexane as eluent to give S-23 as a colorless liquid in 95% (201 mg) yield.
List of Publications
Conferences
