Semiclassical theory of “Optical activity” in the asymmetric top: off resonance

Earlier work on optical activity in pure rotational spectroscopy is generalized to the more realistic model of the asymmetric top. The analog of the Rosenberg dispersion formula for the optical activity parameter, β, is given for the J = 0 state of an asymmetric top. It involves only the coupling to the J = 1 manifold of states. The molecular parameters which determine the presence or absence of optical activity in pure rotational spectroscopy are displayed. These provide a reasonable alternate definition of chirality in the pure rotational region of the spectrum.     

Asymmetric radical polymerization of N-butadiene 1-carboxylyl S(−)-α-phenyl ethyl amine

N-butadiene 1-carboxylyl S(?)-α-phenyl ethyl amine (Bu-1-CPA) was prepared and polymerized in various solvents such as acetonitrile, dimethylformamide (DMF), methanol, dioxane and benzene at 50° using AIBN as initiator. From the i.r. spectra of the polymers, it was confirmed that poly(Bu-1-CPA) was composed of trans 1,4-units. The polymer produced in DMF showed constant optical activity around [α]_D ? 10° (c = 1.0 in DMF) but the polymers obtained in the other solvents showed different optical activity, suggesting that the degree of asymmetric induction depended upon the solvent used during polymerization. From results for the copolymerization of Bu-1-CPA with styrene, it was similarly found that the asymmetric induction occurred in the backbone chain. The proposed mechanism for asymmetric induction involves polymerization via amide-iminol type prototropic tautomerism of Bu-1-CPA.     

Catalytic asymmetric hydrosilylation of ketones by rhodium(I) complexes containing the enantiomers of (R1, R1)-(±)-1,2-phenylenebis(methylphenylarsine) and their phosphorus isosteres

Soluble (bicyclo[2.2.1]hepta-2,5-diene)rhodium(I) complexes containing the enantiomers of (R¹,R¹-(±)-1,2-phenylenebis(methylphenyl-arsine) or its phosphorus isosteres have been found to be highly efficient catalysts for the asymmetric hydrosilylation of prochiral ketones. The rates of reaction for both the bis(tertiary arsine)- and the bis(tertiary phosphine)-containing catalysts appear to be amongst the fastest of their type hitherto reported, with both catalysts giving comparable optical yields of asymmetric silyl ethers. This is the first successful use of a tertiary arsine-containing complex for catalytic asymmetric hydrosilylation. The optical yields varied between 18 – 41% for C₆H₅COCH₃ and CH₃COC(CH₃)₃, depending upon conditions and catalyst, but with o-MeOC₆H₄COCH₃ as substrate, the optical yield dropped to 1 – 2% for both catalysts.     

First asymmetric total synthesis of (+)-curcutetraol

The first asymmetric total synthesis of (+)-curcutetraol, a marine phenolic bisabolane-type sesquiterpene, was achieved in eight steps in ca. 50% overall yield. The chiral tertiary benzylic alcohol moiety in the o-position of a phenol was constructed in high optical yield (99% ee) by an asymmetric synthesis using a chiral aminal, (2R,5S)-2-methoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane.     

Reduction of carbonyl compounds via hydrosilylation: V. Synthesis of optically active allylic alcohols via regioselective asymmetric hydrosilylation

Regioselective asymmetric reduction of prochiral α,β-unsaturated ketones to optically active allylic alcohols was performed via hydrosilylation catalyzed by a rhodium(I) complex with (+)-BMPP, (+)-DIOP and (?)-DIOP as chiral ligands. The allylic alcohols with optical purity up to 69% e.e. were obtained in good yields. The extent of asymmetric induction was found to depend on the stereo-electronic matching of the chiral ligand, ketone and hydrosilane employed. In the asymmetric reduction of (R)-carvone, leading to carveol, the extent of asymmetric induction was found to depend markedly on the ligand/rhodium ratio. Either trans-(5R,1S)-carveol or cis-(5R,1R)-carveol was obtained with good stereoselectivity by using (?)-DIOP or (+)-DIOP as chiral ligand, and it turned out that the chiral center present in carvone had only a slight influence on the asymmetric induction by the chiral catalysts.     

Exploiting the Chiral Ligands of Bis(imidazolinyl)- and Bis(oxazolinyl)thiophenes—Synthesis and Application in Cu-Catalyzed Friedel–Crafts Asymmetric Alkylation

Five new C₂-symmetric chiral ligands of 2,5-bis(imidazolinyl)thiophene (L1–L3) and 2,5-bis(oxazolinyl)thiophene (L4 and L5) were synthesized from thiophene-2,5-dicarboxylic acid (1) with enantiopure amino alcohols (4a–c) in excellent optical purity and chemical yield. The utility of these new chiral ligands for Friedel–Crafts asymmetric alkylation was explored. Subsequently, the optimized tridentate ligand L5 and Cu(OTf)₂ catalyst (15 mol%) in toluene for 48 h promoted Friedel–Crafts asymmetric alkylation in moderate to good yields (up to 76%) and with good enantioselectivity (up to 81% ee). The bis(oxazolinyl)thiophene ligands were more potent than bis(imidazolinyl)thiophene analogues for the asymmetric induction of the Friedel–Crafts asymmetric alkylation.     

Chiral β-dimethylaminoalkylphosphines. Highly efficient ligands for a nickel complex catalyzed asymmetric grignard cross-coupling reaction

Chiral β-dimethylaminoalkylphosphines were prepared starting with amino acids, (S)-alanine, (S)-phenylalanine, (R)-phenylglycine, (S)-valine, and (R)-tert-leucine. The chiral phosphines were found to be highly efficient ligands for a nickel catalyzed asymmetric Grignard cross-coupling reaction (38～94% optical yield).     

Optically active phenanthrolines in asymmetric catalysis. Rhodium-catalyzed asymmetric transfer hydrogenation of acetophenone

The catalyst formed in situ from [Rh(1,5-cyclooctadiene)Cl]₂ and (+)-(S)-3-s-butyl-1,10-phenanthroline promotes the asymmetric transfer hydrogenation of acetophenone in isopropanol solution; optical yields of up to 31% are obtained.     

A new electronically deficient atropisomeric diphosphine ligand (S)-CF3O-BiPhep and its application in asymmetric hydrogenation

A new electronically deficient atropisomeric diphosphine ligand (S)-CF₃O-BiPhep was synthesized from 1-bromo-3-(trifluoromethoxy)benzene in high yield. The key steps included oxidative coupling with anhydrous ferric chloride and optical resolution by (+)-DMTA. The ligand afforded high performance for Ir-catalyzed asymmetric hydrogenation of quinolines with ee up to 92% and TON up to 25,000. It was also successfully applied to the Pd-catalyzed asymmetric hydrogenation of simple indoles with ee up to 87% and Rh-catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone with 97% ee.     

Novel chiral C2-symmetric multidentate aminophosphine ligands for use in catalytic asymmetric reduction of ketones

A series of novel chiral C₂-symmetric multidentate aminophosphine ligands have been successfully synthesized by Schiff-base condensation of bis（o-formylphenyl）phenylphosphane and easily available monoprotected（1R,2R）-diaminocyclohexane.The catalytic properties of these ligands were investigated in Ir-catalyzed asymmetric transfer hydrogenation of various aromatic ketones,giving the corresponding optical active alcohols with up to 98%conversion and good ee under mild reaction conditions.     

Enantioselective total synthesis of (S)-(−)-quinolactacin B

The enantioselective total synthesis of (−)-quinolactacin B (−)-1 was performed in seven steps and 33% overall yield from tryptamine. The synthesis features the use of ruthenium catalytic asymmetric hydrogen reaction to introduce the chirality in dihydro-β-carboline 2. Based on Noyori’s work, the hydrogenation using the (R,R)-TsDPEN-Ru complex produces dihydro-β-carbolines possessing the (S) absolute configuration, the corrected asymmetric center of the natural product. The synthetic quinolactacin B displayed optical rotations that was in accordance with that of the natural product, thereby supporting the (S) configuration for natural quinolactacin B. The final product’s stereochemical assignment is in agreement with that proposed by Nakagawa and co-workers.     

Construction of optical active metallo-supramolecular polymers from enantiopure bis-pybox ligands

Two types of optical active metallo-supramolecular polymers were successfully constructed from the complexation of two enantiopure bis-pyridine-dioxazole (bis-pybox) ligands and 3d transition metal ions such as Zn²⁺ and Fe²⁺ in organic solution. The self-assembly process was investigated via UV–vis and fluorescent titration. The chiral characteristic of polymers was detected by circular dichroism. It was revealed that the phenyl-substituted polymers showed higher stability than the benzyl-substituted ones. Temperature-dependent circular dichroism spectra demonstrated the dynamic structure of this type polymer under the variation of temperature. This work highlights the opportunity in designing and constructing of the optical active metallo-supramolecular polymers from the organic privilege ligands in the field of asymmetric catalysis.     

Synthesis of (αR,βS)-epoxyketones by asymmetric epoxidation of chalcones with cinchona phase-transfer catalysts

An efficient method to synthetically produce optically enriched (αR,βS)-epoxyketones was developed using a quaternary ammonium salt derived from cinchona alkaloid as the chiral phase-transfer catalyst. (αR,βS)-Epoxyketones were prepared in high optical purities (91-99% ee) by the asymmetric epoxidation of 1,3-diarylenones with aqueous sodium hypochlorite in the presence of a hydrocinchonine-derived chiral phase-transfer catalyst bearing a 2,3,4-trifluorobenzyl group.     

Condensation of 1-alkoxy-1,3-butadienes with optically active glyoxylic acid esters

The condensation of 1-alkoxy-1,3-butadienes with optically active esters of glyoxylic acid leading to esters of 2-alkoxy-5,6-dihydro-2H-pyran-6-carboxylic acids was studied and the dependence of asymmetric induction on the following parameters examined: alkoxy group in dienes, dissymetric group in glyoxylates, solvent and the temperature of condensation. The optical yield and absolute configuration of the adducts were determined by optical rotation measurements of methyl malate obtained by degradation. The data are rationalized by postulating parallel formation of four active complexes corresponding to a transoid and cisoid conformation of the glyoxylate ester in the transition state.     

Tocopherol side chain synthesis via asymmetric organocatalytic transfer hydrogenation and convenient measurement of stereoselectivity

An asymmetric synthetic route for 1-iodofarnesane, a key intermediate for tocopherol side chain synthesis, starting from (+)-(R)-citronellal was developed. 1-Iodofarnesane was prepared through eight steps in about 50% overall yield, and asymmetric transfer hydrogenation of the enal with a chiral organocatalyst was conducted as a stereoinduction step. To measure the stereoinduction level and optical purity of the product, a convenient analytical method was developed in which a phenylcarbamate derivative of the C₁₅ alcohol was found to be suitable to give proper polarity and UV-activity for chiral UV-HPLC analysis.     

Enantioselective preparation of (2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids and some derivatives

(2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids (epoxyangelic acids) were prepared from (Z)-2-methyl-2-butenoic acid using the Sharpless asymmetric epoxidation method in combination with the use of (−)- and (+)-menthol as chiral auxiliaries. Both substances, obtained in high enantiomeric excess, were characterized by spectroscopic and optical activity data. Their absolute configuration was determined by correlation with (R)-(+)-2-methyl-1,2-butanediol.     

Mandelate and prolinate ionic liquids: synthesis, characterization, catalytic and biological activity

A group of quaternary ammonium mandelates and l-prolinates, as ionic liquids, were synthesized and characterized. The prepared salts were soluble in water and showed high surface activity. The described synthesis of l-prolinate was simple and the obtained ionic liquid contained a chiral anion. l-Prolinate in CH₂Cl₂ was employed for the asymmetric Michael addition of a ketone to nitrostyrene. A yield of 60%, enantioselectivity (upto 50% ee), and good diastereoselectivity (syn/anti ratio of up to 90:10) were obtained for the asymmetric addition of cyclohexanone. These novel ionic liquids proved to be very effective anti-microbial and anti-fungal agents, especially didecyldimethylammonium l-prolinate. Additionally, it was found that phytotoxicity can be a useful tool in assessing the optical forms of ionic liquids.     

Asymmetric total synthesis of optically active α-curcumene

(R)-(?)-α-Curcumene has been prepared in 66% optical yield and in 34% overall yield in five steps by means of asymmetric Grignard cross-coupling reaction catalyzed by a nickel complex of chiral (aminoalkylferrocenyl)phosphine as a key carbon-carbon bond forming step.     

Asymmetric grignard cross-coupling reaction between (E)-β-bromostyrene and 1-phenylethylmagnesium chloride

Trans-2,3-bis-(diphenylphosphinomethyl)-norbornene-(5), trans-2,3-bis-(diphenylphosphinomethyl)-7-oxanorbornane, and (−)-/2((S)-1-dimethylaminoethyl)-phenyl/-diphenylphosphine have been used as ligands for the nickel and palladium catalyzed asymmetric Grignard cross-coupling reaction giving the coupling product (E)-1,3-diphenyl-1-butene.Chemical yields from 60 to 95% and optical yields up to 40% were obtained, depending on the types of ligand coordinated.     

The synthesis of (+)- and (−)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylarsino)butane and their use in asymmetric catalysis

(+)- and (?)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylarsino)butane, the arsenic analogs of (+)- and (?)-diop have been synthesized in good yields. These ligands give similar optical yields to diop in the asymmetric hydrosilylation of ketones, but lower optical yields for the asymmetric hydrogenation of α-acetamidocinnamic acid, but, in this case, yield the isomer having the opposite configuration to diop.