Terminal Allyl Research Articles

Artemisinin biosynthesis in growing plants of Artemisia annua. A 13CO 2 study

Artemisinin from Artemisia annua has become one of the most important drugs for malaria therapy. Its biosynthesis proceeds via amorpha-4,11-diene, but it is still unknown whether the isoprenoid precursors units are obtained by the mevalonate pathway or the more recently discovered non-mevalonate pathway. In order to address that question, a plant of A. annua was grown in an atmosphere containing 700 ppm of 13CO 2 for 100 min. Following a chase period of 10 days, artemisinin was isolated and analyzed by 13C NMR spectroscopy. The isotopologue pattern shows that artemisinin was predominantly biosynthesized from ( E,E)-farnesyl diphosphate (FPP) whose central isoprenoid unit had been obtained via the non-mevalonate pathway. The isotopologue data confirm the previously proposed mechanisms for the cyclization of ( E,E)-FPP to amorphadiene and its oxidative conversion to artemisinin. They also support deprotonation of a terminal allyl cation intermediate as the final step in the enzymatic conversion of FPP to amorphadiene and show that either of the two methyl groups can undergo deprotonation.

Polyanionic Aryl Ether Metallodendrimers Based on Cobaltabisdicarbollide Derivatives. Photoluminescent Properties

Fluorescent Frechet-type poly(aryl ether) dendrimers that incorporate the 1,3,5-triphenylbenzene as core molecule and 3, 6, 9, or 12 terminal allyl ether groups have been prepared in very good yield by following the Frechet convergent approach. Regiospecific hydrosylilation reactions on the allyl ether functions with the cobaltabisdicarbollide derivative Cs[1,1′-μ-SiMeH-3,3′-Co(1,2-C2B9H10)2] lead to different generations of Fechet-type polyanionic metallodendrimers decorated with 3, 6, and 9 cobaltabisdicarbollide units. Starting dendrimers exhibit photoluminescence properties at room temperature under ultraviolet irradiation; nevertheless, after functionalization with cobaltabisdicarbollide derivatives, the fluorescence properties are quenched. Products are fully characterized by FTIR, NMR, and UV−vis spectroscopies. For metallodendrimers, the UV−vis absorptions have been a good tool for estimating the experimental number of cobaltabisdicarbollide units peripherally attached to the dendrimeric structure...

Rapid, Selective Ru-Sulfonate-Catalyzed Allylation of Indoles Using Alcohols as Substrates

The Ru-catalyzed allylation of differing indole compounds using ArCH(OH)CH═CH2 (Ar = Ph, 2-CH3C6H4, 2-CH3OC6H4 2-ClC6H4, and 1-naphthyl) is relatively fast (usually <30 min for 100% conversion) at ambient temperature in the presence of [Ru(Cp*)(CH3CN)3](PF6) + a sulfonic acid cocatalyst, RSO3H (R = p-tolyl, a camphor fragment or CH3). The new catalysts allow allyl alcohols rather than carbonates, halides, acetates, etc., to be used as substrates in this allylation chemistry, thereby avoiding the use of a (wasted) leaving group. The branched products are favored, and in a number of examples b/l ratios in excess of 20 are observed. The catalyst is selective in that there is little or no N-allylation. The use of acids such as CF3SO3H or HBF4 results in slower and/or less selective reactions. Although phosphoric acid additives show some promise, carboxylic acids are much less effective or do not catalyze the reaction at all. The preformed isolated complexes [Ru(Cp*)(η3-C3H5)(RSO3)2] are efficient catalyst precursors; however, NMR experiments suggest that one of the active species is the monosulfonate cationic complex [Ru(Cp*)(η3-C3H5)(CH3CN)(RSO3)]+. Stoichiometric oxidative addition reactions are shown to be relatively rapid. New Ru(Cp*) complexes have been generated and characterized by NMR methods. DFT calculations suggest that the large b/l ratios observed have a structural basis in that the Ru−C(allyl) bond length for the substituted terminal allyl carbon, Ru−C(1), is relatively long. X-ray structures for Ru(Cp*)(η3-C3H5)(SO4) and the dication [Ru(Cp*)(η3-C3H5)(H2O)2]2+ (as a camphor sulfonate salt) are reported.

Structure-Based Rationale for Selectivity in the Asymmetric Allylic Alkylation of Cycloalkenyl Esters Employing the Trost ‘Standard Ligand’ (TSL): Isolation, Analysis and Alkylation of the Monomeric form of the Cationic η3-Cyclohexenyl Complex [(η3-c-C6H9)Pd(TSL)]+

The solution-phase structures of the monomeric forms of the cationic Pd-eta(3)-allyl and Pd-eta(3)-cyclohexenyl complexes [Pd(R,R)-1(eta(3)-C(3)H(5))](+) (7(+)) and [Pd(R,R)-1(eta(3)-C(6)H(9))](+) (8(+)) bearing the trans-cyclohexylenediamine-based Trost 'Standard Ligand' (R,R)-1 have been elucidated by NMR, isotopic labeling and computation. In both complexes, (R,R)-1 is found to adopt a C(1)-symmetric conformation, leading to a concave shape in the 13-membered chelate in which one amide group in the chiral scaffold projects its NH unit out of the concave surface in close vicinity to one allyl terminus. The adjacent amide has a reversed orientation and projects its carbonyl group out of the concave face in the vicinity of the opposite allyl terminus. Stoichiometric and catalytic asymmetric alkylations of [8(+)][X(-)] by MCHE(2) (E = ester, M = 'escort' counterion, X = Pd allyl counterion) show the same selectivities and trends as have been reported for in situ-generated catalysts, and a new model for the enantioselectivity has been explored computationally. Three factors are found to govern the regioselectivity (pro-S vs pro-R) of attack of nucleophiles on the eta(3)-C(6)H(9) ring in 8(+) and thus the ee of the alkylation product: (i) a pro-R torquoselective bias is induced by steric interaction of the eta(3)-C(6)H(9) moiety with one phenyl ring of the ligand; (ii) pro-S delivery of the nucleophile can be facilitated by hydrogen-bonding with the concave orientated amide N-H; and (iii) pro-R delivery of the nucleophile can be facilitated by escort ion (M) binding to the concave orientated amide carbonyl. The latter two opposing interactions lead to the selectivity of the alkylation being sensitive to the identities of X(-) and M(+). The generation of 8(+) from cyclohexenyl ester substrate has also been explored computationally. The concave orientated amide N-H is able to activate the leaving group of the allylic ester by hydrogen bonding to its carbonyl group. However, this interaction is only feasible for the (S)-enantiomer of substrate, leading to the prediction of a powerful kinetic resolution (k(S) >> k(R)), as is found experimentally. This new model involving two regiochemically distinct (NH) and (CO) locations for nucleofuge or nucleophile binding, may prove of broad utility for the interpretation of the selectivity in asymmetric allylic alkylation reactions catalyzed by Pd complexes of (R,R)-1 and related ligands.

Comparison of an Internally Coordinated 2-Pentenyllithium with Its 4-Sila Analog. Structure and Dynamic Behavior: Unexpected 13C7Li Spin Coupling

Four allylic lithium compounds have been prepared with a tethered ligand, (CH(3)OCH(2)CH(2))(2)NCH(2)C(CH(3))(2)-L, attached to a terminal allyl carbon. They are equimolar equilibrium mixtures of 3-endo-L-allyllithium with 3-exo-L-allyllithium, 9en and 9ex, respectively, and (separately) 1-exo-TMS-3-endo-L-allyllithium with 1-exo-TMS-3-exo-L-allyllithium, 13en and 13ex, respectively. Carbon-13 NMR analysis shows that all four compounds are monomeric and internally coordinated, the allyl moiety in each one is partially localized, and (7)Li is spin coupled to both (31)C(1) and (13)C(2) of allyl. NMR line shape changes show that 9en, 9ex, 13en, and 13ex all undergo fast transfer of the lithium-coordinated ligand between faces of the allyl planes at low temperatures. Within each equilibrium system the compound with the exo-tethered ligand inverts faster than its endo analog. All four compounds invert faster in THF-d(10) compared to in diethyl ether-d(10) as solvent. Corresponding Eyring activation parameters are reported. Also, inversion in THF-d(8) for all four compounds is characterized by large negative DeltaS(double dagger) values, whereas in diethyl ether-d(10) DeltaS(double dagger) values for inversion are near neutral. NMR line shape changes due to the dynamics of bimolecular C,Li exchange and rotation around the C(2)-C(3) bonds are just detected via selective line broadening effects above 290 K. These processes are much slower than inversion.

Arylallylic Lithium Compounds, Internally versus Externally Coordinated: Comparison of Their Structures and Dynamic Behavior via X-ray Crystallography and NMR

A comparison of externally coordinated arylallyllithiums with internally coordinated arylallyllithiums using a combination of X-ray and NMR studies shows that 2-bis(2-methoxyethyl)aminomethyl-1-phenylallyllithium 7, and 2-bis(2-methoxyethyl)aminomethyl-1,3-diphenylallyllithi um 8, are indeed fully internally coordinated with all phenyls endo, and lithium is close to one terminal allyl carbon. By contrast, among the externally coordinated analogs 1-phenylallyl-lithium.(HMPT)4 5, and 1-phenylallyllithium.(THF) 6, both phenyls are exo and the proximity of lithium to anion was only detected in compound 6. Lithium-7 NMR clearly identifies the Li(HMPT)4+ complex in 5, whereas a 7Li{1H} HOESY experiment reveals 7Li to be coordinated to THF in 6 and close to the PhC terminal allyl carbon. Carbon-13 NMR shows that all of the above compounds are fully delocalized despite differences among the sites of lithium and their separations from the anions. Changes in the 13C NMR line shapes show that the diphenyl compound 8 undergoes a very fast 1,3-lithium sigmatropic shift, and all of the phenyls in the above compounds undergo fast rotation around their phenyl Cipso-Callyl bonds. Barriers to rotation, DeltaH from NMR line shapes for 5, 6, 7, and 8 respectively, are 19.8, 14.6, 10.2, and 8.9 kcal x mol-1. The decrease in barriers is clearly correlated with a decrease in separation of lithium from an allyl terminal carbon and implies that especially among the latter three, 6, 7, and 8, lithium is involved in the mechanism for phenyl rotation. This question is discussed.

Electronic differentiation competes with transition state sensitivity in palladium-catalyzed allylic substitutions

Electronic differentiations in Pd-catalyzed allylic substitutions are assessed computationally from transition structure models with electronically modified phospha-benzene-pyridine ligands. Although donor/acceptor substitutions at P and N ligand sites were expected to increase the site selectivity, i.e. the preference for "trans to P" attack at the allylic intermediate, acceptor/acceptor substitution yields the highest selectivity. Energetic and geometrical analyses of transition structures show that the sensitivity for electronic differentiation is crucial for this site selectivity. Early transition structures with acceptor substituted ligands give rise to more intensive Pd-allyl interactions, which transfer electronic P,N differentiation of the ligand more efficiently to the allyl termini and hence yield higher site selectivities.

Regio- and Diastereoselective Decarboxylative Coupling of Heteroaromatic Alkanes

Allylic esters of heteroaromatic alkanes undergo facile palladium-catalyzed decarboxylative coupling. The resulting C−C bond is formed with high diastereoselectivity and high regioselectivity for coupling at the more substituted allyl terminus. It is proposed that this unusual combination of selectivities results from a tandem allylation/aza-Cope rearrangement sequence. After allylation, decarboxylative dearomatization produces an intermediate for the aza-Cope rearrangement. The subsequent aza-Cope rearrangement occurs under mild conditions because it is driven by rearomatization.

Photoluminescence of PMMA doped with fluorescein and carbosilane dendrimer and lasing in PBG resonance cavity

Carbosilane dendrimers with terminal allyl groups were synthesized and used to encapsulate the allyl derivative of fluorescein (allyl-FL) doped in PMMA. The optical property of this system was investigated and the results showed that the concentration of allyl-FL in PMMA could be increased to 4.5 wt% without decrease of the luminescence efficiency by adding the dendrimer into the system. The allyl-FL/dendrimer/PMMA film was embedded into a resonance cavity composed of two pieces of photonic band gap (PBG) materials to form a new-type solid-state laser. A laser emission at 589 nm was obtained when excited with a third harmonic generation (THG) of a pulsed Nd:YAG laser (355 nm) and its full-width at half-maximum of the spectrum was 1.7 nm.

Rhodium-Catalyzed Hydroallylation of Activated Alkenes

Rhodium-catalyzed hydroallylation of activated alkenes have been reported. This concept is manipulated by a one-pot operation of neutral components, an allylic carbonate, an α,β-unsaturated ketone or ester and a hydrosilane, which are activated in a specific order by [Rh(cod){P(OPh)3}2]OTf (2e, cod = 1,5-cyclooctadiene) under almost neutral conditions. In the absence of rhodium catalyst, no reaction proceeds at all. In this procedure, a variety of γ,δ-unsaturated ketones or esters are obtained in a moderate to an excellent yield. For example, slow addition of 3-methoxycarbonyloxy-1-phenyl-1-butene (4) in CH2Cl2 to a solution of methyl methacrylate (7a), diethylmethylsilane (8), and 1 mol % of 2e in CH2Cl2 afforded a mixture of methyl 5-phenyl-2,2,3-trimethyl-4(E)-pentenoate (9a) and methyl 2,2-dimethyl-3-phenyl-4(E)-hexenoate (10a) in 93% yield. Although the distinction between the two allylic termini during the hydroallylation with linear carbonate is relatively difficult, introduction of a trialkylsilyl group to either of the two allylic termini is a powerful tool for regioselective allylation, which preferentially proceeds at the terminus opposite the one bearing a trialkylsilyl group.

Deconvoluting the Memory Effect in Pd‐Catalyzed Allylic Alkylation: Effect of Leaving Group and Added Chloride

An analysis of product distributions in the Tsuji-Trost reaction indicates that several instances of reported "memory effects" can be attributed to slow interconversion of the initially formed syn- and anti-[Pd(eta3-allyl)] complexes. Addition of chloride triggers a true memory effect, in which the allylic terminus originally bearing the leaving group has a higher reactivity. The latter effect, termed regioretention, can be rationalized by ionization from a palladium complex bearing a chloride ion, forming an unsymmetrically substituted [Pd(eta3-allyl)] complex. DFT calculations verify that the position trans to the phosphine ligand is more reactive both in the initial ionization and in the subsequent nucleophilic attack.

Palladium-Catalyzed Coupling of Allylboronic Acids with Iodobenzenes. Selective Formation of the Branched Allylic Product in the Absence of Directing Groups

Palladium-catalyzed coupling reactions of functionalized allylboronic acids with iodobenzenes were achieved under standard Suzuki-Miyaura coupling conditions. The coupling reactions afforded selectively the branched allylic products in high to excellent yields. In contrast to palladium-catalyzed nucleophilic substitution reactions proceeding via (eta3-allyl)palladium intermediates, this process does not require directing groups in the allyl moiety to achieve substitution at the congested allylic terminus. The regioselectivity of the process was largely unaffected by the substituent effects of the iodobenzenes and the allylic substrates.

Perturbation of Conjugation in Internally Solvated Allylic Lithium Compounds: Variation of Ligand Structure. NMR and X-ray Crystallography

Several allyic lithium compounds were prepared with different potential ligands tethered at C2. These are with CH3OCH2CH2NCH3CH2-, 5 and 1-TMS 6, with (CH3)2NCH2CH2NCH3CH2-, 1-TMS 7, and with ((CH3)2NCH2CH2)2NCH2-, 8 and 1-TMS 9. In all these compounds Li is fully coordinated to the pendant ligand and is sited off the axis perpendicular to the allyl plane at one of the allyl termini as indicated by a combination of X-ray crystallography and NMR spectra. Compounds 5 and 8 are Li-bridged dimers as shown by X-ray crystallography and also dimeric in benzene solution as determined from freezing point determinations. Compounds 6, 7, and 9 are monomeric in THF-d8 or diethyl ether-d10 solution and exhibit one bond 13C1, 6Li scalar coupling at low temperature. Taken together the crystallographic and NMR data indicate that all of these compounds incorporate partially delocalized allylic moieties. Compounds 5 and 8 undergo fast 1,3-Li-sigmatropic shifts that are proposed to take place within low concentrations of monomers in fast equilibrium with prevalent dimers. Averaging with increasing temperature of the one-bond 13C, 6Li coupling constant in 6, 7, and 13 provided the dynamics of bimolecular C-Li exchange with Delta H++ values of 6.7, 12, and 13 kcal x mol(-1), respectively. Averaging of the diastereotopic N(CH3)2 13C resonances of 7 is indicative of fast transfer of coordinated ligand between faces of the allyl plane Delta H++ = 5.3 kcal x mol(-1) combined with slower inversion at nitrogen. Compound 8 exhibits similar effects. It is concluded that variation of the ligand structure changes dynamic behavior of the compounds but has little influence of their degrees of delocalization.

Star-Shaped Poly(tetrahydrofuran) with Reactive End Groups: Design, MALDI-TOF Study, and Solution Behavior

Star-shaped poly(tetrahydrofuran) (PTHF) with up to six allyl end groups was prepared by living cationic ring-opening polymerization. A functional initiation system, using allyl alcohol and trifluoromethanesulfonic anhydride, was used, followed by end-capping of the living polymer chains with the multifunctional termination agent tris(2-aminoethyl)amine. In this way, star-shaped PTHF with allyl end groups could be synthesized, with varying molecular weight (6000−20 000 g·mol-1) and number of arms (three to six). Subsequently, the terminal allyl functions were quantitatively transformed into hydroxy groups using a hydroboration procedure. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis, NMR, and size exclusion chromatography confirmed the controlled synthesis of these reactive star-shaped structures. MALDI-TOF was successfully used to determine the absolute molecular weight and purity of star-shaped polymers. They were further characterized by viscosimetry measurements, and their properties were compared to their linear analogues. For the same molecular weight, the stars had a strong reduced viscosity in solution.

PGSE NMR Diffusion, Overhauser, and DFT Studies on the Salts [Pd(η3-CH3CHCHCHPh)(dppe)](anion)

PGSE NMR diffusion, Overhauser and DFT studies on the salts [Pd(η3-CH3CHCHCHPh)(dppe)](anion) (dppe = 1,2-bis(diphenylphosphino)ethane, anion = BF4-, CF3SO3-, BArF-, PF6-) are reported. In dichloromethane solution there is little or no ion pairing for the BArF derivative, whereas the other three anions show intermediate degrees of ion pairing. In chloroform solution the CF3SO3- and BArF- salts show complete ion pairing. The 19F,1H HOESY studies reveal a selective approach of the CF3SO3- and PF6- anions with respect to the allyl ligand. The approach brings the anion somewhat closer to the allyl phenyl ring than to the allyl methyl group. Further, the anion approaches the Pd center from the side of the two terminal allyl protons. The anions are not attracted to the allyl ligand but rather are choosing both an electronically (allyl phenyl vs allyl methyl) and sterically (terminal allyl protons vs central allyl proton) preferred pathway toward the P and metal atoms. This result is partially rationalized via D...

Decarboxylative Claisen Rearrangement Reactions of Allylic Tosylmalonate Esters.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Polymeric Topological Isomers through Double Metathesis Condensation with H‐Shaped Telechelic Precursors

AbstractSummary: An H‐shaped poly(tetrahydrofuran), poly(THF), having four terminal allyl groups was prepared through the covalent conversion of an ionically linked polymer assembly, comprised of four units of cationic poly(THF) having a pyrrolidinium salt and an allyl end group, and one unit of anionic poly(THF) having two dicarboxylate end groups. A pair of polymeric topological isomers, having double‐cyclic, manacle, and θ‐shaped constructions, was subsequently produced under dilution through the intramolecular double metathesis condensation of four terminal allyl groups of the H‐shaped precursor.The formation of manacle‐shaped and θ‐shaped architectures by the intramolecular double metathesis condensation of an H‐shaped poly(tetrahydrofuran) with four terminal allyl groups.magnified imageThe formation of manacle‐shaped and θ‐shaped architectures by the intramolecular double metathesis condensation of an H‐shaped poly(tetrahydrofuran) with four terminal allyl groups.

X-ray, 13C NMR, and DFT Studies on a Ruthenium(IV) Allyl Complex. Explanation for the Observed Control of Regioselectivity in Allylic Alkylation Chemistry

X-ray, 13C NMR, and DFT studies on the cationic Ru(IV) allyl complex Ru(Cp*)Cl(CH3CN)(η3-PhCHCHCH2), as a PF6 salt, have revealed a marked asymmetry in the bonding of the allyl ligand, which can be interpreted as arising from differences in π-bonding from the metal center to the two terminal allyl carbons. This asymmetry in the bonding is offered as an explanation for the observed control of regioselectivity in the Ru-catalyzed allylic alkylation reaction.

Decarboxylative Claisen Rearrangement Reactions of Allylic Tosylmalonate Esters

[reaction: see text] Two different combinations of silylating agent and base are used for one-pot [3,3]-sigmatropic rearrangement-decarboxylation reactions of tosylmalonic mono(allylic) esters under mild conditions, providing the products of formal regiospecific allylation of methyl tosylacetate at the more substituted allylic terminus.

Photocuring of a thiol‐ene system based on an unsaturated polyester

AbstractTo produce a photocurable thiol‐ene system, unsaturated polyester was prepared from the condensation reaction of ethylene glycol, diethylene glycol, and fumaric acid. Diallyl groups were introduced into the ends of the unsaturated polyester by a sequential condensation reaction. The coating formulation studied contained an equimolar ratio of thiol and vinyl groups of the prepared unsaturated polyester, including 1 wt % Irgacure 184. The curing behaviors of the unsaturated polyester with multifunctional thiols were investigated using real‐time FTIR spectroscopy. The rates of disappearance of thiol and vinyl groups of the unsaturated polyester were similar, demonstrating that there was little free‐radical homopolymerization of the internal fumaric group or the end‐capped vinyl ether group during the photocuring process and that the thiol‐ene reaction is the dominant process. The kinetics of the model compounds demonstrated that the reaction of the terminal allyl double bond with the thiyl radical is faster than that of the internal fumaric double bond in the UV curing of the unsaturated polyester. The storage stability of the thiol‐ene system based on unsaturated polyester was effectively increased by the addition of N‐PAL. The Raman spectra revealed that the presence of a multifunctional thiol (penta 3‐MP4) in the coating formulation increased the degree of surface curing due to the chain‐transfer ability of the thiyl radical. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 342–350, 2005