Chiral Alkoxy Groups Research Articles

Development of a Chiral N-Alkoxyamide Strategy and Application to the Asymmetric Total Synthesis of Fasicularin

AbstractThe asymmetric total synthesis of fasicularin by a chiral N-alkoxyamide strategy is reported. Incorporation of the chiral alkoxy group onto an amide nitrogen changes the original reactivity of the amide, enabling two key transformations: aza-spirocyclization and the reductive Strecker reaction. DFT calculations indicate that pyramidalization of the N-alkoxyamide nitrogen is crucial to produce a cyclic hemiaminal in equilibrium, which undergoes aza-spirocyclization. The chiral alkoxy group is also used as a stereocontrol element to establish two consecutive stereocenters. The iridium-catalyzed reductive Strecker reaction of the N-alkoxylactam provides the aminonitrile with high diastereoselectivity.

Asymmetric Total Synthesis of Fasicularin by Chiral N-Alkoxyamide Strategy.

The asymmetric total synthesis of fasicularin is reported. The key to success is the use of a chiral N-alkoxyamide to control both reactivity and stereoselectivity. This functional group enables the aza-spirocyclization and the reductive Strecker reaction, which cannot be realized with an ordinary amide. In addition, use of the chiral alkoxy group establishes two consecutive stereocenters in the aza-spirocyclization through remote stereocontrol.

Mechanistic insights into the tropo-inversion of the biphenyl moiety in chiral bis-amido phosphites and in their palladium(ii) complexes.

Chiral bis-amido phosphites L1 and L2 containing a diaminobiphenyl unit and a chiral alkoxy group derived from either (-)-menthol or 3-acetoxy deoxycholic methyl ester have been synthesised. Both L1 and L2 react with PdCl2(NCPh)2 affording di- or mononuclear derivatives with formula trans-[Pd(μ-Cl)Cl(L)]2 (1a, L = L1; 1b, L = L2) or trans-PdCl2(L)2 (2a, L = L1; 2b, L = L2) depending on the Pd : L molar ratio. The crystal structure of (M,P)-1a confirms the trans arrangement of the ligand L1 and shows an unusual puckering of the Pd2(μ-Cl)2 core (θ 46°). Both the ligands L1 and L2 and their complexes (1 and 2) are fluxional in solution as a consequence of the tropo-inversion of the diaminobiphenyl unit. For L1, L2, 1a and 2a a combined study including variable temperature 31P{1H} NMR spectroscopy and line shape analysis, Eyring plots and DFT calculations have shed light on the mechanism of the tropo-inversion.

Conformational chirality of the biphenyl groups induced by the aggregation of poly{bis[4-(4’-(S)-2-methylbutoxy)-biphenoxy] phosphazene}

Poly{bis[4-(4’-(S)-2-methylbutoxy)biphenyloxy]phosphazene}(PP-C) was designed and successfully synthesized, and then characterized by means of FT-IR spectroscopy, 1H- and 31P-NMR, GPC spectroscopy, wide angle X-ray diffraction and differential scanning calorimetry. The results indicated that for PP-C, the Mw is 2.18×105 and the PDI is 1.96. PP-C was a kind of crystallized polymer with a crystallizing point of -2.0 °C and a melting point of 28 °C. The conformational chirality of the PP-C molecules was studied using circular dichroism spectrum. It was found that in dilute THF solution, the biphenyl groups in the PP-C molecules twisted randomly. However, when the PP-C formed aggregates, the biphenyl groups tended to twist single-handedly, which was controlled by the adjacent chiral alkoxy groups.

Stereoselective synthesis of 1-methoxyspiroindoline phytoalexins and their amino analogues

The stereoselective synthesis of the spiroindoline phytoalexin (R)-(+)-1-methoxyspirobrassinin and its unnatural (S)-(−)-enantiomer were achieved by the bromine-induced spirocyclization of 1-methoxybrassinin using chiral auxiliaries (+)- and (−)-menthol, followed by oxidation of the obtained menthyl ethers. The TFA-catalyzed methanolysis of chiral 1-methoxyspirobrassinol menthyl ethers provided (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether and its other three unnatural stereoisomers. The enantiomers of the 2-amino analogues of the indole phytoalexin (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether were prepared by the TFA-catalyzed replacement of the chiral alkoxy group with an amine. The synthesized compounds were tested in vitro on cancer cell lines and examined with enantiopure 2-amino analogues of the indole phytoalexin (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether, which showed in most cases, lower activity than the corresponding racemates.

Long range chirality transfer in free radical polymerization of vinylterphenyl monomers bearing chiral alkoxy groups

ABSTRACTTwo series of chiral bulky vinyl aromatics, 2‐(4'‐alkoxyphenyl)‐5‐(4'‐hexyloxyphenyl)styrene (S‐Am (m = 0, 1, 2, 3)/R‐A0) and 2‐(4'‐hexyloxyphenyl)‐5‐(4'‐alkoxyphenyl)styrene (S‐Bm (m = 0, 1, 2, 3)/R‐B0), were synthesized and radically polymerized (where m denotes the carbon number between stereogenic center and ether oxygen atom). The generation and stereomutation of helical structures as well as chirality transfer from the stereogenic center of the side‐group to the polymer backbone during polymerization were investigated by a combination of 1H‐ and 13C‐NMR, polarimetry, circular dichroism spectroscopy, liquid crystal induced circular dichroism, and computer simulation. All the polymers, except S‐B3, display optical rotations and Cotton effects in the UV‐Vis absorption region of terphenyl pendant, which are quite different from the corresponding model compounds and monomers, suggesting the formation of chiral secondary structures, that is, skewed packing of side‐groups and twisting of polymer backbones with a dominant screw sense. The sign of optical rotation changes alternatively and the strength diminishes when m increases from 1 to 3. However, although the stereogenic centers in S‐A0 and S‐B0 are closer to the vinyl group than those in S‐A1 and S‐B1, separately, a weaker chiral induction power is observed. Moreover, optical rotations of polymers derived from S‐A0/R‐A0 and S‐B0/R‐B0 are opposite in sign and increase with annealing time in tetrahydrofuran. These results are in a sharp contrast with our previous findings in similar vinylterphenyl compounds, where ‐COO‐ rather than ‐O‐ links the chiral alkyl tail to the terphenyl group, manifesting a remarkable effect of small structural variation of side‐group on polymer chiroptical properties and complexity of chirality transfer in helix‐sense‐selective polymerization. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3674–3687

Effects of local dipoles on the chiroptical properties of chiral oligo(phenyleneethynylene)s: Large g values for annealed films of chiral oligo(phenyleneethynylene) bearing alkoxy and bromo-substituents

The effects of local dipole on the chiroptical properties of chiral conjugated oligomers were investigated by comparative studies on two analogous chiral oligo(phenyleneethynylene)s: Myr-OPE-Br and Myr-OPE. Myr-OPE-Br carries local dipoles introduced by electron-accepting Br-groups and electron-donating chiral alkoxy-groups, while Myr-OPE only carries chiral alkoxy groups. The DSC thermogram of Myr-OPE-Br showed a glass transition at ∼80 °C and a cold crystallization centered at 120 °C, while Myr-OPE only showed a glass transition at ∼90 °C. Thermal annealing treatment showed significant effects on the absorption and CD spectra of spin-coated film of Myr-OPE-Br: with annealing above 100 °C, the absorption maximum exhibited an obvious red shift; the absorption bands displayed well-resolved vibronic structures; the CD spectrum was inversed compared to those with no annealing or annealing at 80 °C; and the g abs value of the annealed film increased with increasing annealing temperature and time. After annealing at 140 °C for 1 h, a maximum g abs value above 0.117 was observed for Myr-OPE-Br film. While for Myr-OPE, the thermal annealing treatment showed no obvious effect on both the absorption and CD spectra. The CD spectra of both the as-coated film and annealed film of Myr-OPE showed no obvious Cotton effect. The observed large g values as well as the thermochromic changes in the absorption and CD spectra of annealed Myr-OPE-Br films were attributed to the presence of local dipoles.

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

The asymmetric synthesis of gymnastatin H has been achieved by using the photoisomerisation of a conjugated ester to its β,γ-unsaturated isomer through the protonation of a in situ generated dienol as key step. Thanks to diacetone D-glucose used as a chiral alkoxy group, the protonation occurred well onto one of the two diastereotopic faces with very high yields and selectivities. Moreover, by this way the configuration of the C-6 centre of the target molecule was controlled.

Modular Approach to New Chiral Monodentate Diamidophosphite Ligands. Application in Palladium-Catalyzed Asymmetric Hydrovinylation of Styrene

A new group of chiral monodentate diamidophosphite ligands (2 P−N/1 P−O bond) based on diazaphospholidine backbones derived from N,N′-dibenzylcyclohexane-1,2-diamine (7) and N,N′-dimethylcyclohexane-1,2-diamine (8), and diazaphosphepine backbones derived from N,N′-dimethyl-[1,1′-binaphthyl]-2,2′-diamine (9) and various chiral alkoxy groups (coming from phenylethanol a, borneol b, methyllactate c, allylic alcohol d, and methanol e) were prepared. The ligands have a highly modular structure, which is well suited to the synthesis of a small library. Preparation was readily accomplished by the successive addition of pure enantiomeric substituted diamine and pure enantiomeric alcohol to phosphorus trichloride. The corresponding diamidophosphite selenides Se(7−9) were prepared and the JPSe was calculated in order to evaluate the σ-donor ability of the new ligands. The reaction of [Pd(μ-Cl)(η3-2-CH3C3H4)]2 with the new diamidophosphite ligands (7−9) led to the monomeric allylic neutral complexes 11−13. Two isomers appeared in solution due to the R- or S-geometry around the palladium atom. The molecular structure determined by X-ray diffraction of the neutral complex [PdCl(η3-2-CH3C3H4)(7a)] (11a-(S,S,Sal)) showed a nonsymmetric coordination of the allyl moiety due to the greater trans influence of the phosphorus atom. The asymmetric hydrovinylation reaction between styrene and ethylene was tested using filtered CH2Cl2 solutions of [PdCl(η3-2-CH3C3H4)L] complexes and AgBF4 as catalytic precursors. The reaction performed at 15 °C and 15 bar of ethylene starting pressure led to good selectivities and moderate to good activities of 3-phenyl-1-butene. The best results were obtained when the cationic catalytic precursor contained the 9b-(R,Sal) diamidophosphite with a binaphthyl backbone and bornyloxy as the third substituent. With this system the TOF reached 595 h−1 of 3-phenyl-1-butene, whereas the ee was 90% toward the R-isomer.

Synthesis and polymerization behavior of various substituted half-sandwich titanium complexes Cp′TiCl2(OR∗) as catalysts for syndiotactic polystyrene

A new set of chiral alkoxy substituted half-sandwich titanium complexes of Cp'TiCl 2 (OR * )(Cp' = Cp, CH 3 CH(CH 3 )Cp, CH 3 OCH 2 CH 2 Cp, CH 3 OCH 2 CH(CH 3 )Cp; R * = menthyl, fenchyl) were synthesized, characterized and tested as catalyst precursors for the syndiospecific polymerization of styrene. The structure of complex 8 was confirmed by X-ray crystallography. When chiral alkoxy groups took the place of chlorine atom, it was found that the intramolecular coordination of the oxygen on Cp ring to the titanium disappeared in the solid state. Under the same conditions, complexes 1-4 showed higher activity, and complexes 5-8 showed lower activity than CpTiCl 3 . The catalytic activity increased in the order 8 < 7 < 6 < 5 < CpTiCl 3 < 4 < 3 < 2 < 1. The highest activity was 7.37 x 10 7 g s-PS/(mol Ti mol S h) for complex 1/methylaluminoxane (MAO) at a molar ratio of Al/Ti = 2000. Kinetic measurements of the polymerization were carried out at different temperature for complex 1. The effects of variation on temperature, Al/Ti ratio for catalytic activity and syndiotactic polystyrene (s-PS)% were also studied.

Synthesis of Optically Active Arylcyclopentanes by Carbocyclisation of ω-Alkenylbenzyllithiums Involving Diastereofacial Differentiation

ω-Alkenylbenzyllithiums, bearing a chiral alkoxy group in suitable position cyclise to arylcyclopentanes with very high control of the relative stereochemistry and very high stereofacial differentiation. This reaction has been used in the synthesis of enantiopure arylcyclopentanes derivatives.

Studies on asymmetric conversion of arenes to functionalized cyclohexenones via chiral auxiliary-promoted nucleophilic additions to arene-chromium complexes

Reactions of alkoxyarene-chromium tricarbonyl complexes, having chiral alkoxy groups, with isobutyronitrile anion, followed by standard work-up produces substituted alkoxycyclohexadienes with diastereomeric excesses of up to 76%. Conversion to cyclohexenones allows recovery of the chiral alcohol auxiliary. The absolute stereochemistry of the product from the optimum procedure was determined by using Mosher's method on the derived cyclohexenol.

Fluoroalkoxyphosphonium ylids. Epimerization and transformations

Dehydrofluorination of alkoxydifluorophosphoranes 2, containing chiral alkoxygroup, by organometallic bases passes under conditions of kinetic control to afford diastereomeres of ylid 3 in the proportion 1:1. In the presence of lithium salts the epimerization of 3 leads to the formation of the most thermodynamic stable diastereomere. Hydrolysis and reaction of 3 with alcohols affords phosphinates 6, reaction with acids provides fluorophosphinates 7.

Reaction of chromium (Fischer) carbenes and sulfilimines

The photochemical reactions of alkoxychromium (Fischer) carbenes and sulfilimines lead to imidates in fair to excellent yields. Aromatic, heteroaromatic, and alkylsulfilimines, the latter bearing functional groups such as cyano, sulfone, ether, ester, and dioxolane groups, gave the corresponding imidates in good to excellent yield. However, acyl- and sulfonyl-substituted sulfilimines did not react with chromium carbenes, except for sulfilimines bearing ethoxycarbonyl and phtalimidylamino groups. A variety of differently substituted chromium carbene complexes bearing alkyl, cycloalkyl, styryl, alkyl, and alkynyl groups attached either at the carbene carbon or at the oxygen also gave imidates in good yields. For α,β-unsaturated carbenes, the exclusive 1,2-addition of the sulfimine nitrogen was observed at room temperature, in contrast to the behavior of other nitrogen nucleophiles which are reported to add in 1,4-fashion under these reaction conditions. In turn, optically active imidates of the type ArN=C(OR * )Me [R * = chiral substituent derived from (R)-(+)-1-phenyl-1-butanol, l-(-)-menthol, (1S)-endo-(-)-borneol, and (1R)-(-)-myrtenol] can be prepared efficiently by utilizing the corresponding chiral alkoxy group on the carbene moiety. The reactions above also occur in the dark but reaction times are considerably longer. N-Halosulfilimines reacted with alkoxychromium carbenes to yield N-acylsulfimines instead of the expected N-haloimidates. Based upon a set of thermal and photochemical reactions between N-haloimidates and diphenyl sulfide in the absence of chromium complexes, the complex (CO) 5 CrNCMe is proposed to be responsible for this novel reaction of N-haloimidates and diphenyl sufide

α-tributylstannylacetals: Preparation via transacetalisation of diethoxymethyltributyltin, and use for the synthesis of new α-stannylated ethers

The transacetalisation of readily available diethoxymethyltributyltin affords a large variety of new α-stannylacetals, which are expected to have a high potential for selective organic synthesis when they contain labile or chiral alkoxy groups. The α-stannylacetals can be converted into the corresponding substituted α-stannyl-ethers by treatment with organoaluminium halides or by use of an acetyl chloride/Grignard reagent sequence. The study has concentrated on allylic, homoallylic, and homopropargylic derivatives, which offer the best potential for organic synthesis.

Unexpectedly high diastereomeric induction in the diels-alder reaction of quinones with chiral aryl containing 1-alkoxy-3-trimethylsilyloxybuta-1,3-dienes.

Chiral 1-alkoxy-3-trimethylsilyloxybuta-1,3-dienes induce a high diastereomeric excess in the cycioaddition with quinones when the chiral alkoxy group is of the type OCH(CH 3)R with R = aryl. Also forR =vinyl. CH 2OCH 3 the found induction is higher than that observed for R = ten. butyl. The highest diastereomeric excess (>95%) was achieved in the cycloaddifion of 1-[1-(p-methoxyphenyl)-ethoxy]-3-trimethylsilyloxybuta-1,3-diene with benzoquinone. An explanation is given based on the assumption that the R substituent is suongly enlarged in size by complexation with the used quinones.

Asymmetric diels-alder reactions with chiral alkoxycyclohexadienes

Excellent diastereofacial discriminations have been observed for the addition of 1,4-naphthoquinone to alkoxycyclohexa-1,3-dienes subject to appropriate selection of a chiral alkoxy group.

ChemInform Abstract: Silicon‐Functionalized Silyl Enol Ether. Part 2. Silyl Enol Ethers Bearing Stereogenic Silicon Atoms and Chiral Alkoxy Groups: The Effect of These Groups Upon the Facial Selectivity of the Epoxidation of an Enol Double Bond.

AbstractThe lithium enolates (III), derived from the ketones (I), react with the dichlorosilanes (IV) to produce the chlorosilyl enol ethers (V).

Silicon-functionalized silyl enol ethers. Part 2. Silyl enol ethers bearing stereogenic silicon atoms and chiral alkoxy groups: the effect of these groups upon the facial selectivity of the epoxidation of an enol double bond

Silicon-functionalized silyl enol ethers. Part 2. Silyl enol ethers bearing stereogenic silicon atoms and chiral alkoxy groups: the effect of these groups upon the facial selectivity of the epoxidation of an enol double bond