Chiral Initiators Research Articles

Macromolecular helicity control of poly(phenyl isocyanate)s with a single stimuli-responsive chiral switch.

The introduction of a single chiral substituent with a switchable conformer equilibrium at the poly(phenyl isocyanate) terminus allowed the control of the helical sense of the polymer backbone using various external stimuli. Helical sense enhancement was achieved through a domino effect, where the helical sense was assigned by VCD spectroscopy and DFT calculations.

Rationalization of Asymmetric Amplification via Autocatalysis Triggered by Isotopically Chiral Molecules

Asymmetric amplification induced in the Soai autocatalytic reaction by chiral initiators that are enantiomeric only by virtue of an isotope, e.g., −CH3 vs CD3–, is examined by spectroscopic, kinetic, and DFT modeling studies to help understand requirements for the emergence of biological homochirality. We find that the initiator inhibits the autocatalytic pathway at the outset of the reaction but ultimately provides the imbalance required for asymmetric amplification. This work provides clues in the ongoing search for prebiotically plausible versions of asymmetric autocatalysis.

Synthesis of One-Handed Helical Block Copoly(substituted acetylene)s Consisting of Dynamic cis-transoidal and Static cis-cisoidal Block: Chiral Teleinduction in Helix-Sense-Selective Polymerization Using a Chiral Living Polymer as an Initiator.

By using a living one-handed helical cis-transoidal poly(chiral substituted phenylacetylene) as a polymer initiator (poly(1n)), helix-sense-selective polymerization (HSSP) of an achiral phenylacetylene 2 having two hydroxy groups successfully afforded a diblock copoly(phenylacetylene) (copoly(1n/2m)) consisting of a dynamic one-handed helical cis-transoidal block and a static one-handed helical cis-cisoidal block. The formation of the diblock structure was confirmed by consumption of the chiral initiator, appearance of characteristic CD indicating the one-handed helical cis-cisoidal block, and occurrence of the selective photocylic aromatization reaction in the cis-cisoidal block. Therefore, HSSP has been achieved by using the chiral alkenyl groups in the initiator as a chiral source for the first time. In addition, since the HSSP was achieved in spite of the long distance between the chiral initiation site and the propagating site, chiral teleinduction through the rigid and static one-handed helical cis-cisoidal block based on domino effects was confirmed.

Asymmetric Induction by a Nitrogen 14N/15N Isotopomer in Conjunction with Asymmetric Autocatalysis

AbstractChirality arising from isotope substitution, especially with atoms heavier than the hydrogen isotopes, is usually not considered a source of chirality in a chemical reaction. An N2,N2,N3,N3‐tetramethyl‐2,3‐butanediamine containing nitrogen (14N/15N) isotope chirality was synthesized and it was revealed that this isotopically chiral diamine compound acts as a chiral initiator for asymmetric autocatalysis.

Asymmetric Induction by a Nitrogen 14 N/15 N Isotopomer in Conjunction with Asymmetric Autocatalysis.

Chirality arising from isotope substitution, especially with atoms heavier than the hydrogen isotopes, is usually not considered a source of chirality in a chemical reaction. An N 2 ,N 2 ,N 3 ,N 3‐tetramethyl‐2,3‐butanediamine containing nitrogen (14N/15N) isotope chirality was synthesized and it was revealed that this isotopically chiral diamine compound acts as a chiral initiator for asymmetric autocatalysis.

Copolymerization of Cyclic Esters Controlled by Chiral NNO-Scorpionate Zinc Initiators

Reaction of the chiral alcohol-scorpionate compound bpzteH [bpzteH = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1-para-tolylethanol] with [ZnR2] (R = Me, CH2SiMe3) in a 1:2 molar ratio afforded the dinuclear chiral alkyl zinc complexes [Zn(R)(κ2-NNμ-O)Zn(R)2] (1 and 2) [κ2-NNμ-O = bpzte, R = Me 1, CH2SiMe3 2]. Subsequent alcoholysis reaction with ArOH (1 equiv; Ar = 2,6-C6H3Me2) yielded the chiral dinuclear zinc complexes [(ZnR)2(κN:κN-μ-O)(μ-OAr)] (3 and 4) [κN:κN-μ-O = bpzte, R = Me 3, CH2SiMe3 4]. The X-ray crystal structures of 1 and 3 confirmed a dinuclear structure in all complexes, with the alkoxide of the heteroscorpionate ligands in a μ-bridging mode between the two Zn(II) centers. The zinc complexes 1–4, bearing trisalkyl and alkyl-aryloxide ligands, are shown to function as highly efficient single-component initiators for the ring-opening homopolymerization of e-caprolactone and l-/rac-lactide. These initiators enable rapid polymerization at ambient temperatures, affording materials with low molecular w...

Asymmetric polymerization of N-vinylcarbazole with optically active anionic initiators

The anionic polymerization of N-vinylcarbazole (NVC) by using optically active anionic initiators such as the lithium salts of (S)-1-(9H-fluoren-2-yl)-4-isopropyl-4,5-dihydrooxazole ((S)-1-FIDH) and (S)-2-(9H-fluoren-2-yl)-4- isopropyl-4,5-dihydrooxazole ((S)-2-FIDH) and complexes of (-)-Sparteine with n-butylithium (n-BuLi-(-)-Sp) or fluorenyl lithium (FILi-(-)-Sp) was achieved. The yield and specific rotation of poly(N-vinylcarbazole)s (poly(NVC)s) were considerably affected by the molar ratio of (S)-FIDH to NVC. The highest yield and specific rotation were obtained with Li- (S)-1-FIDH as an initiator, with a molar ratio of monomer and initiator [M]/[I] = 10/1. The effects of the chiral initiators, type of solvent and the polymerization temperature were investigated. The obtained optical activity of polymers was attributed to asymmetric induction of the chiral initiators.

Carbon Anionic Chiral Initiators for Asymmetric Anionic Polymerization of Achiral Isocyanates.

Novel optically active carbon anionic initiators bearing a chiral oxazole substituent on fluorene ring, (S)-1-(9H-fluoren-2-yl)-4-isopropyl-4, 5-dihydrooxazole lithium ((S)-1-FIDD-Li) and (S)-2-(9H-fluoren-2-yl)-4-isopropyl-4, 5-dihydrooxazole lithium ((S)-2-FIDD-Li), were synthesized. Anionic polymerizations of achiral polyisocyanates with the chiral initiators were investigated and optical rotation of the obtained polymers were attributed to asymmetric induction of the chiral initiators. The crowded substituent of initiator ((S)-2-FIDD-Li) seems to reduce the polymerizability of isocyanates and yet enhances the chiral induced ability in polymerization.

Asymmetric induction by retgersite, nickel sulfate hexahydrate, in conjunction with asymmetric autocatalysis

A chiral crystal of retgersite, nickel sulfate hexahydrate, acts as a chiral initiator of asymmetric autocatalysis, affording highly enantiomerically enriched pyrimidyl alkanols.

Homopolymerization and copolymerization of N‐substituted maleimides with chiral anionic initiators

AbstractNovel optically active anionic initiators bearing a chiral oxazole substituent on the fluorene ring, (S)‐1‐(9H‐fluoren‐2‐yl)‐4‐isopropyl‐4,5‐dihydrooxazole lithium (Li‐(S)‐1‐FIDH) and (S)‐2‐(9H‐fluoren‐2‐yl)‐4‐isopropyl‐4,5‐dihydrooxazole lithium (Li‐(S)‐2‐FIDH), were prepared. Anionic homopolymerizations of achiral N‐substituted maleimide (RMI) with the chiral initiators were investigated. The optically active polymers obtained were attributed to asymmetric induction of the chiral initiators. The very crowded chiral initiator Li‐(S)‐1‐FIDH was found to play a better asymmetric induction role in the polymers than Li‐(S)‐2‐FIDH. Anionic copolymerization of (R)‐(+)‐N‐1‐phenylethyl maleimide and optically inactive RMI with Li‐(S)‐1‐FIDH were also studied. © 2014 Society of Chemical Industry

Asymmetric autocatalysis of pyrimidyl alkanol and its application to the study on the origin of homochirality.

CONSPECTUS: Amplification of enantiomeric excess (ee) is a key feature for the chemical evolution of biological homochirality from the origin of chirality. We describe the amplification of ee in the asymmetric autocatalysis of 5-pyrimidyl alkanols in the reaction between diisopropylzinc (i-Pr2Zn) and pyrimidine-5-carbaldehydes. During the reaction, an extremely low ee (ca. 0.00005% ee) can be amplified to >99.5% ee, and therefore, the initial slightly major enantiomer is automultiplied by a factor of ca. 630000, while the initial slightly minor enantiomer is automultiplied by a factor of less than 1000. In addition, pyrimidyl alkanols with various substituents at the 2-position of the pyrimidine ring, 3-quinolyl alkanol, 5-carbamoyl-3-pyridyl alkanol, and large multifunctionalized pyrimidyl alkanols also act as highly efficient asymmetric autocatalysts in the addition of i-Pr2Zn to the corresponding aldehydes. The asymmetric autocatalysis of pyrimidyl alkanol can discriminate the chirality of various compounds. Chiral substances such as alcohols, amino acids, hydrocarbons, metal complexes, and heterogeneous chiral materials can act as chiral triggers for asymmetric autocatalysis to afford pyrimidyl alkanols with the corresponding absolute configuration of the initiator. This recognition ability of chiral compounds is extremely high, and chiral discrimination of a cryptochiral quaternary saturated hydrocarbon was established by applying asymmetric autocatalysis. By using the large amplification effect of the asymmetric autocatalysis, we can link various proposed origins of chirality with highly enantioenriched organic compounds in conjunction with asymmetric autocatalysis. Thus, a statistical fluctuation in ee of racemic compounds can be amplified to high ee by using asymmetric autocatalysis. Enantiomeric imbalance induced by irradiation of circularly polarized light can affect the enantioselectivity of asymmetric autocatalysis. The asymmetric autocatalysis was also triggered by the morphology of inorganic chiral crystals such as quartz, sodium chlorate, and cinnabar. Chiral organic crystals of achiral compounds also act as chiral initiators, and during the study of a crystal of cytosine, enantioselective chiral crystal phase transformation of the cytosine crystal was achieved by removal of the water of crystallization in an achiral monohydrate crystal. Enantioselective C-C bond formation was realized on the surfaces of achiral single crystals based on the oriented prochirality of achiral aldehydes. Furthermore, asymmetric autocatalysis of pyrimidyl alkanols is a highly sensitive reaction that can recognize and amplify the significantly small effect of a chiral compound arising solely from isotope substitution of hydrogen, carbon, and oxygen (D/H, (13)C/(12)C, and (18)O/(16)O). These examples show that asymmetric autocatalysis with an amplification of chirality is a powerful tool for correlating the origin of chirality with highly enantioenriched organic compounds. Asymmetric autocatalysis using two β-amino alcohols reveals a reversal of enantioselectivity in the addition of i-Pr2Zn to aldehyde and is one approach toward understanding the mechanism of asymmetric dialkylzinc addition, where heteroaggregates act as the catalytic species.

Partial Kinetic Resolution of Oxanorbornenes by Ring-Opening Metathesis Polymerization with a Chiral Ruthenium Initiator.

We report the first kinetic resolution by ring-opening metathesis polymerization (KR-ROMP). The polymerization profile showed a solvent-dependent variation of selectivity (S) over the course of the reaction. In tetrahydrofuran and dichloromethane, the resolution selectivity increased over the course of the reaction, while in toluene the selectivity was much higher in the beginning of the reaction and decreased throughout. Evidence suggests that the change in selectivity might be attributed to the chiral secondary structure of the growing polymer chain.

Enantioselective Synthesis Induced by the Helical Molecular Arrangement in the Chiral Crystal of Achiral Tris(2-hydroxyethyl) 1,3,5-Benzenetricarboxylate in Conjunction with Asymmetric Autocatalysis

Abstract 5-Pyrimidyl alkanol with an enantiomeric excess of up to >99.5% was formed using chiral crystals of achiral tris(2-hydroxyethyl) 1,3,5-benzenetricarboxylate as a chiral initiator. In the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde, the helicity of the molecular arrangement of achiral tricarboxylate in the crystalline state could be successfully used as a source of chirality to afford enantioenriched alkanol in conjunction with asymmetric autocatalysis with amplification of enantiomeric excess.

Helix-sense-selective Polymerization of Substituted Acetylenes by Using an Isolated Rh Chiral Initiator with an Amino Acid Ligand

Abstract Helix-sense-selective polymerization (HSSP) of substituted acetylenes by using an isolated chiral Rh initiator with an amino acid ligand has been achieved. The sense of the helix of the main chain of the resulting polymer was controlled by the sign of the chirality of the ligand. The isolated initiator needed less of the chiral ligand and gave polymers having a higher [θ] value than the two component chiral initiator systems we reported previously. The resulting polymers had a higher Mw.

ChemInform Abstract: Asymmetric Autocatalysis Triggered by Chiral Crystals Formed from Achiral Compounds and Chiral Isotopomers

AbstractReview: 77 refs.

Reversal in enantioselectivity induced by achiral alcohols in asymmetric autocatalysis in the presence of a chiral diol as a chiral initiator

A reversal in enantioselectivity was observed by the combination of a chiral diol and achiral alcohols as a chiral initiator in the asymmetric alkylation of a pyrimidine-5-carbaldehyde using diisopropylzinc. (2S,3S)-Butane-2,3-diol alone induced (R)-pyrimidyl alkanol, while a mixture of the chiral diol and phenol derivatives induced (S)-pyrimidyl alkanol. The effect of achiral alcohols is also discussed.

Asymmetric Autocatalysis Triggered by Chiral Crystals Formed from Achiral Compounds and Chiral Isotopomers

AbstractAsymmetric autocatalysis with amplification of enantiomeric excess is found in the enantioselective addition of diisopropylzinc to pyrimidine‐5‐carbaldehyde using pyrimidyl alkanol as an asymmetric autocatalyst. Asymmetric autocatalysis has been employed as a method for clarifying the origin of homochirality. Circularly polarized light, inorganic chiral crystals and statistical fluctuation of enantiomeric imbalance act as chiral initiators in asymmetric autocatalysis to afford highly enantioenriched products. We have investigated asymmetric autocatalysis using chiral crystals formed from achiral and racemic compounds as an origin of chirality. Absolute control of the crystal chirality of cytosine was achieved by the removal of crystal water. Enantioselective carbon‐carbon bond formation at the enantiotopic crystal face of aldehydes was established using diisopropylzinc vapor. In addition, asymmetric autocatalysis triggered by chiral compounds arising from H, C and O isotope substitution has been achieved.

“Governing initiation-supporting termination” in chiral poly(n-hexyl isocyanate)

Poly(n-hexyl isocyanate) (PHIC) with varying molecular weights were synthesized using a chiral initiator and chiral terminator by living anionic polymerization. In such PHICs, chirality of the initiator plays a decisive role in determining the helical sense of the entire polymeric chain, whereas chirality of the terminator plays a supportive role.

Synthesis of Several Chiral Atom Transfer Radical Polymerization Initiators and Its Helix-sense-selective Initiating Function for ATRP

Five optically active alkyl bromides were synthesized and were used as chiral atom transfer radical polymeriza- tion (ATRP) initiators for the helically selective polymerization of 1-phenyldibenzosuberyl methacrylate (PDBSMA). In order to avoid the racemization of the primary free radical formed in initiating step, the optically active alkyl bromide initia- tors were designed as such a structure in which the bromine atom did not connect to the chiral center. The chiral ATRP ini- tiators tested here are (S)-2,2'-di(bromomethyl)-1,1'-binaphthyl, (S)-2-bromomethyl-2-methyl-1,1'-binaphthyl, menthyl α-bromophenylacetate, N-menthyl α-bromophenylacetamide and (3β,5α)-cholestan-3-yl α-bromo phenylacetate. (S)-2,2'- Di(bromomethyl)-1,1'-binaphthyl, (S)-2-bromomethyl-2-methyl-1,1'-binaphthyl and menthyl α-bromophenylacetate were synthesized following the method reported by literatures. N-menthyl α-bromophenylacetamide was synthesized by adding dropwise the solution of α-bromophenylacetyl chloride in tetrahydrofuran (THF) into the mixture of menthylamine, triethyl- amine and THF with stirring at room temperature within 3 h and stirring at room temperature for another 8 h after the addi- tion. (3β,5α)-Cholestan-3-yl α-bromo phenylacetate was synthesized using the method for the synthesis of menthyl α-bromophenylacetate except using (3β,5α)-cholestanol instead of menthol. The poly-PDBSMA obtained from the ATRP initiated by the optically active alkyl bromides was fractionated into THF-soluble part and THF-insoluble part. THF-soluble part was optically active. By studying the chiroptical properties of the THF-soluble part of the poly-PDBSMA and by com- paring the optical rotation of the THF-soluble part of the poly-PDBSMA with that of the poly(methyl methacrylate) (poly-MMA) obtained under the same polymerization condition, we concluded that the ATRP initiated by the optically active alkyl bromides was helix-sense selective. The NMR study of poly-MMA derived from the THF-insoluble part showed that the polymer produced from the polymerization initiated by (S)-2,2'-di(bromomethyl)-1,1'-binaphthyl was isotactic, which proved further that the ATRP initiated by the optically alkyl bromines was helix-sense selective. Among the five optically active alkyl bromides, (S)-2,2'-di(bromomethyl)-1,1'-binaphthyl and (S)-2-bromomethyl-2-methyl-1,1'-binaphthyl had the best helical selectivity. The helix-sense selectivity depended on the polymerization temperature. The ceiling temperature is 70 ℃. In the range of 0—70 ℃, the helix-sense selectivity increased with the increase of the polymerization temperature. Keywords atom transfer radical polymerization; chiral alkylbromide; helix-sense-selective; helical polymer

Asymmetric anionic polymerizations of 7-cyano-7-alkoxycarbonyl-1,4-benzoquinone methides

Asymmetric anionic polymerizations of 7-cyano-7-alkoxycarbonyl-1,4-benzoquinone methides (1) with various alkoxy groups were performed using chiral initiators such as lithium isopropylphenoxide (iPrPhOLi)/(S)-(–)-2,2′-isopropylidene-bis(4-phenyl-2-oxazoline) ((–)-PhBox) and lithium isopropylphenoxide (iPrPhOLi)/(–)-sparteine ((–)-Sp) to investigate the effect of the alkoxy groups of alkoxycarbonyl substituent in the monomers 1 and chiral ligands of chiral initiators on the control of chiral center in the formation of polymers. Molar optical rotation values of the polymers were significantly dependent upon alkoxy groups, and the polymers with higher molar optical rotation were obtained in monomers with primary alkoxy groups. The asymmetric anionic oligomerizations of the quinone methides having methoxy(1a), ethoxy(1b), and n-propoxy(1c) groups with chiral initiators were carried out. Both 1-mers and 2-mers were isolated and their optical resolutions were performed to determine the extent of stereocontrol. High stereoselectivity was observed at the propagation reaction, but not at the initiation reaction. The effect of the counterion on the control of chiral center in the formation of the polymer was investigated in the asymmetric anionic polymerizations of 1b with iPrPhOM(M = Li, Na, K)/(–)-Sp and iPrPhOM(M = Li, Na, K)/(–)-PhBox initiators and discussed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011