General base and general acid catalyzed intramolecular aminolysis of esters. Cyclization of esters of 2-aminomethylbenzoic acid to phthalimidine

Plots of log k(0) vs pH for the cyclization of trifluoroethyl and phenyl 2-aminomethylbenzoate to phthalimidine at 30 degrees C in H(2)O are linear with slopes of 1.0 at pH >3. The values of the second-order rate constants k(OH) for apparent OH(-) catalysis in the cyclization reactions are 1.7 x 10(5) and 5.7 x 10(7) M(-)(1) s(-)(1), respectively. These rate constants are 10(5)- and 10(7)-fold greater than for alkaline hydrolysis of trifluoroethyl and phenyl benzoate. The k(OH) for cyclization of the methyl ester is 7.2 x 10(3) M(-)(1) s(-)(1). Bimolecular general base catalysis occurs in the intramolecular nucleophilic reactions of the neutral species. The value of the Bronsted coefficient beta for the trifluoroethyl ester is 0.7. The rate-limiting step in the general base catalyzed reaction involves proton transfer in concert with leaving group departure. The mechanism involving rate-determining proton transfer exemplified by the methyl ester in this series (beta = 1.0) can then be considered a limiting case of the concerted mechanism. General acid catalysis of the neutral species reaction or a kinetic equivalent also occurs when the leaving group is good (pK(a) 相似文献   

Ruthenium-catalyzed cyclization of alkyne-epoxide functionalities through alternation of the substituent and structural skeleton of epoxides

Treatment of 1-(o-ethynylphenyl)-2-alkyl-2-aryl epoxides with TpRuPPh(3)(CH(3)CN)(2)PF(6) catalyst (10 mol %) in hot toluene (100 degrees C, 12 h) led to an atypical cyclization and gave 1-aryl-2-alkyl-1H-indene derivatives and carbon monoxide efficiently. The cyclization of 1-cis-enynyl-2-alkyl epoxides with this catalyst in hot toluene (10 mol %, 100 degrees C, 12 h) gave 2,5-disubstituted phenols in 45-72% yields. Under the same conditions, 1-cis-enynyl- 2,2-dialkyl epoxides and 1-cis-enynyl- 2-alkyl-2-aryl epoxides gave the corresponding 6,6-disubstituted cyclohexa-2,4-dien-1-ones in good yields (85-91%). Mechanisms for these new cyclization reactions are proposed on the basis of trapping experiments and isotope labeling experiments. The formation of 1H-indene products likely involves ruthenium-acyl intermediates whereas cyclohexa-2,4-dien-1-ones are thought to derive from ruthenium-ketene intermediates.     

Syntheses and thermal reactivities of tetradentate metalloenediynes of Cu(II) and Zn(II)

The syntheses and Bergman cyclization temperatures of disubstituted tetradentate enediyne ligands based on a dibenzylethylenediamine backbone are reported relative to the corresponding Cu(II) and Zn(II) analogues. For these compounds, the R-groups dimethylamine (dma), pyridine (py), quinoline (quin), and 3-oxypyridine (pyO) have been symmetrically and asymmetrically incorporated at the alkyne termini positions directly (0:0) or via a methylene spacer (1:0, 0:1, 1:1). Electron paramagnetic resonance (EPR) reveals that all Cu(II) complexes are monomeric with near axial symmetry and g-values (g(x) approximately 2.04, g(y) approximately 2.09 g(z) approximately 2.25) representative of tetragonal Cu(II) geometries. The hyperfine splitting parameter A(z) values are approximately 170 x 10(-)(4) cm(-)(1), which is consistent with distorted 4-coordinate, or weakly 6-coordinate, structures. In contrast, solution conductivity measurements show that Zn(II) complexes with rigid py or quin ligands (e.g., py-py 0:0, py-quin 0:0) behave as 1:4 electrolytes indicative of dimeric, bridging enediyne structures. Consequently, these Zn(II) complexes have very high Bergman cyclization temperatures (>290 degrees C), while their less rigid, 1:1 analogues (<185 degrees C) and monomeric Cu(II) counterparts (110-136 degrees C) have markedly lower cyclization temperatures. The results underscore the important consequences metal center structure plays in influencing Bergman cyclization temperatures of metalloenediynes.     

Asymmetric intramolecular cyclopropanation of diazo compounds with metallosalen complexes as catalyst: structural tuning of salen ligand

Intramolecular cyclopropanation of alkenyl α-diazoacetates and alkenyl diazomethyl ketones was examined by using optically active (ON⁺)Ru(II)(salen) and Co(II)(salen) complexes as catalysts. For the cyclization of 2-alkenyl α-diazoacetates, Co(II)(salen) complexes 9 and 10 were found to be superior catalysts to the corresponding (ON⁺)Ru(II)(salen) complexes 4 and 5. On the other hand, (ON⁺)Ru(II)(salen) complex 2 was found to be the catalyst of choice for the cyclization of 3-alkenyl diazomethyl ketones, and complex 4 was found to be a good catalyst for the cyclization of (E)-4-alkenyl diazomethyl ketones. The present study demonstrates that metallosalen complexes, especially optically active (ON⁺)Ru(II)(salen) and Co(II)(salen) complexes, can serve as efficient catalysts for the cyclization of alkenyl diazocarbonyl compounds, if a suitable salen ligand is used as the chiral auxiliary.     

Synthesis of a dialuminum-substituted silicotungstate and the diastereoselective cyclization of citronellal derivatives

A novel dialuminum-substituted silicotungstate TBA(3)H[gamma-SiW(10)O(36){Al(OH(2))}(2)(mu-OH)(2)] x 4 H(2)O (1, TBA = tetra-n-butylammonium) was synthesized by the reaction of the potassium salt of [gamma-SiW(10)O(36)](8-) (SiW10) with 2 equiv of Al(NO(3))(3) in an acidic aqueous medium. It was confirmed by the X-ray crystallographic analysis that compound 1 was a monomer of the gamma-Keggin dialuminum-substituted silicotungstate with the {Al(2)(mu-OH)(2)} diamond core. The cluster framework of 1 maintained the gamma-Keggin structure in the solution states. The reaction of 1 with pyridine yielded TBA(3)[(C(5)H(5)N)H][gamma-SiW(10)O(36){Al(C(5)H(5)N)}(2)(mu-OH)(2)] x 2 H(2)O (2), and the molecular structure was successfully determined by the X-ray crystallographic analysis. In compound 2, two of three pyridine molecules coordinated to the axial positions of aluminum centers and one of them existed as a pyridinium cation, showing that compound 1 has two Lewis acid sites and one Br?nsted acid site. Compound 1 showed high catalytic activity for the intramolecular cyclization of citronellal derivatives such as (+)-citronellal (3) and 3-methylcitronellal (4) without formation of byproduct resulting from etherification and dehydration. For the 1-catalyzed cyclization of 3, the diastereoselectivity toward (-)-isopulegol (3a) reached ca. 90% and the value was the highest level among those with reported systems so far. The reaction rate for the 1-catalyzed cyclization of 3 decreased by the addition of pyridine, and the cyclization hardly proceeded in the presence of 2 equiv of pyridine with respect to 1. On the other hand, the reaction rate and diastereoselectivity to 3a in the presence of 2,6-lutidine were almost the same as those in the absence. Therefore, the present cyclization is mainly promoted by the Lewis acid sites (aluminum centers) in 1. DFT calculations showed that the formation of the transition state to produce 3a is sterically and electronically more favorable than the other three transition states for the present 1-catalyzed cyclization of 3.     

Organolanthanide-catalyzed intramolecular hydroamination/cyclization/bicyclization of sterically encumbered substrates. Scope, selectivity, and catalyst thermal stability for amine-tethered unactivated 1,2-disubstituted alkenes

This paper reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amine-tethered unactivated 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines using coordinatively unsaturated complexes of the type (eta(5)-Me(5)C(5))(2)LnCH(TMS)(2) (Ln = La, Sm), [Me(2)Si(eta(5)-Me(4)C(5))(2)]SmCH(TMS)(2), and [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2) (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2) mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and good to excellent yield. In addition, chiral C(1)-symmetric organolanthanide catalysts of the type [Me(2)Si(OHF)(CpR*)]LnN(TMS)(2) (OHF = eta(5)-octahydrofluorenyl; Cp = eta(5)-C(5)H(3); R* = (-)-menthyl; Ln = Sm, Y), and [Me(2)Si(eta(5)-Me(4)C(5))(CpR*)]SmN(TMS)(2) (Cp = eta(5)-H(3)C(5); R* = (-)-menthyl) mediate asymmetric intramolecular hydroamination/cyclization of amines bearing internal olefins and afford chiral 2-substituted piperidine and pyrrolidine in enantioselectivities as high as 84:16 er at 60 degrees C. The substrate of the structure NH(2)CH(2)CMe(2)CH(2)CH=CH(CH(2))(2)CH=CH(2) is regiospecifically bicyclized by [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2) to the corresponding indolizidine skeleton in good yield and high diastereoselectivity. Thermolysis of (eta(5)-Me(5)C(5))(2)LaCH(TMS)(2) in cyclohexane-d(12) at 120 degrees C rapidly releases CH(2)(SiMe(3))(2) and leads to possible formation of fulvene (eta(6)-Me(4)C(5)CH(2)-) species. The thermolysis product readily reverts to active catalysts upon protonolysis by substrate and exhibits the same catalytic activity as the (eta(5),eta(1)-Me(5)C(5))(2)LaCH(TMS)(2) precatalyst at 120 degrees C in the cyclization of cis-2,2-dimethylhept-5-enylamine. Catalytically-active lanthanide-amido complexes (eta(5)-Me(5)C(5))(2)La(NHR)(NH(2)R)(n) and [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]Sm(NHR)(NH(2)R)(n) are shown to be thermally robust species.     

3,3'-Bis(trisarylsilyl)-substituted binaphtholate rare earth metal catalysts for asymmetric hydroamination

Chiral 3,3'-bis(trisarylsilyl)-substituted binaphtholate rare earth metal complexes (R)-[Ln{Binol-SiAr3}(o-C6H4CH2NMe2)(Me2NCH2Ph)] (Ln = Sc, Lu, Y; Binol-SiAr3 = 3,3'-bis(trisarylsilyl)-2,2'-dihydroxy-1,1'-binaphthyl; Ar = Ph (2-Ln), 3,5-xylyl (3-Ln)) and (R)-[La{Binol-Si(3,5-xylyl)3}{E(SiMe3)2}(THF)2] (E = CH (4a), N (4b)) are accessible via facile arene, alkane, and amine elimination. They are efficient catalysts for the asymmetric hydroamination/cyclization of aminoalkenes, giving TOF of up to 840 h(-1) at 25 degrees C for 2,2-diphenyl-pent-4-enylamine (5c) using (R)-2-Y. Enantioselectivities of up to 95% ee were achieved in the cyclization of 5c with (R)-2-Sc. The reactions show apparently zero-order rate dependence on substrate concentration and first-order rate dependence on catalyst concentration, but rates depend on total amine concentrations. Activation parameters for the cyclization of pent-4-enylamine using (R)-2-Y (deltaH(S)(double dagger) = 57.4(0.8) kJ mol(-1) and deltaS(S)(double dagger) = -102(3) J K(-1) mol(-1); deltaH(R)(double dagger) = 61.5(0.7) kJ mol(-1) and deltaS(R)(double dagger) = -103(3) J K(-1) mol(-1)) indicate a highly organized transition state. The binaphtholate catalysts were also applied to the kinetic resolution of chiral alpha-substituted aminoalkenes with resolution factors f of up to 19. The 2,5-disubstituted aminopentenes were formed in 7:1 to > or = 50:1 trans diastereoselectivity, depending on the size of the alpha-substituent of the aminoalkene. Rate studies with (S)-1-phenyl-pent-4-enylamine ((S)-15e) gave the activation parameters for the matching (deltaH(double dagger) = 52.2(2.8) kJ mol(-1), deltaS(double dagger) = -127(8) J K(-1) mol(-1) using (S)-2-Y) and mismatching (deltaH(double dagger) = 57.7(1.3) kJ mol(-1), deltaS(double dagger) = -126(4) J K(-1) mol(-1) using (R)-2-Y) substrate/catalyst combination. The absolute configuration of the Mosher amide of (2S)-2-methyl-4,4-diphenyl-pyrrolidine and (2R)-methyl-(5S)-phenyl-pyrrolidinium chloride, prepared from (S)-15e, were determined by crystallographic analysis. Catalyst (R)-4a showed activity in the anti-Markovnikov addition of n-propylamine to styrene.     

Ruthenium-catalyzed cyclization of epoxide with a tethered alkyne: formation of ketene intermediates via oxygen transfer from epoxides to terminal alkynes

Treatment of (o-ethynyl)phenyl epoxides with TpRuPPh(3)(CH(3)CN)(2)PF(6) (10 mol %) in hot toluene (100 degrees C, 3-6 h) gave 2-naphthols or 1-alkylidene-2-indanones very selectively with isolated yields exceeding 72%, depending on the nature of the epoxide substituents. Surprisingly, the reaction intermediate proved to be a ruthenium-pi-ketene species that can be trapped efficiently by alcohol to give an ester compound. This phenomenon indicates a novel oxygen transfer from epoxide to its terminal alkyne catalyzed by a ruthenium complex. A plausible mechanism is proposed on the basis of reaction products and the deuterium-labeling experiment. The 2-naphthol products are thought to derive from 6-endo-dig cyclization of (o-alkenyl)phenyl ketene intermediates, whereas 1-alkylidene-2-indanones are given from the 5-endo-dig cyclization pathway.     

Mn(III)-based oxidative free-radical cyclizations of substituted allyl alpha-methyl-beta-ketoesters: syntheses,DFT calculations,and mechanistic studies

The cyclizations of the substituted allyl alpha-methyl-beta-ketoester radicals 11, 14, and 18 were studied by the DFT method at the UB3LYP/6-31G level; the results show that the cis cyclization is easier than the corresponding trans cyclization, but the generated cis radicals are not necessarily more stable than the corresponding generated trans radicals after the cyclizations. The free-radical cyclizations of 11, 14, and 18 in the presence of Mn(OAc)(3) in acetic acid or acetonitrile are all reversible and operate under thermodynamic control, and stereoselectivity of the cyclizations depends on relative stability of the cyclization-generated radicals. Therefore, the oxidative free-radical cyclization of allyl alpha-methyl-beta-ketoester 5a with Mn(OAc)(3) gives a cis product as a major product, while the same oxidative free-radical cyclizations of substituted allyl alpha-methyl-beta-ketoesters 5b and 5c with Mn(OAc)(3) produce trans products as major products.     

Novel synthesis and oxidizing ability of tropylium ions annulated with two 2,4-dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-diones

Convenient preparation of novel tropylium ions annulated with two 2,4-dimethylfuro[2,3-d]pyrimidine-1(2H),3(4H)-diones, 12a(+).BF(4)(-) and 12b(+)().BF(4)(-), consists of a reaction of 2-methoxytropone with dimethylbarbituric acid to give 7,9-dimethyl-3-[1',3'-dimethyl-2'(1'H),4'(3'H),6'(5'H)-trioxopyrimidin-5'-ylidene]cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dione 8 and the following oxidative cyclization by using DDQ or photoirradiation under aerobic conditions. On the basis of the MO calculations, the selectivity of two types of oxidative cyclization reactions of 8 was rationalized. X-ray crystal analyses and MO calculations were carried out to clarify the structural characteristics of 12a(+). BF(4)(-) and 12b(+).BF(4)(-). The stability of cations 12a(+) and 12b(+) is expressed by the pK(R) + values which were determined spectrophotometrically as 8.8 and 8.6. The electrochemical reduction of 12a(+) and 12b(+) exhibited reduction potential at -0.63 and -0.62 (V vs Ag/AgNO(3)), respectively. Reactions of 12a(+)().BF(4)(-) and 12b(+)().BF(4)(-) with some nucleophiles, hydride and diethylamine, were carried out to clarify that the reactivity of 12a(+)().BF(4)(-) and 12b(+).BF(4)(-) was substantially dependent on the annulating position. The oxidizing ability of 12a(+).BF(4)(-) and 12b(+).BF(4)(-) toward alcohols and amines in the autorecycling process was demonstrated as well.     

5-Endo-trig radical cyclizations: disfavored or favored processes?

Relative kinetic data were determined for the 5-endo-trig cyclization of radical 12 compared to hydrogen abstraction from (TMS)(3)SiH in the temperature range of 344-430 K, which allows for the estimation of a rate constant of 2 x 10(4) s(-)(1) at 298 K with an activation energy of ca. 9 kcal/mol for the cyclization process. The 5-endo-trig cyclization of a variety of radicals that afford five-membered nitrogen-containing heterocycles was addressed computationally at the UB3LYP/6-31G level. The 5-endo vs 4-exo mode of cyclication and the effect of delocalization of the unpaired electron in the transition state were investigated. Because the ring formed during cyclization contains five sp(2) centers, electrocyclization via a pentadienyl-like resonance form was also considered. For comparison, similar calculations were performed for 4-penten-1-yl and related radicals. The factors that affect the activation energies of homolytic 5-endo-trig cyclization were determined. In the absence of steric or conformational effects, the endo cyclization to form the five-membered ring was strongly favored over exo cyclization to form the four-membered ring not only on thermodynamic grounds but also kinetically. When a substituent on the double bond was able to delocalize the unpaired electron in the transition state of the 4-exo path, the two modes of cyclization became kinetically comparable. These results have an important bearing on the generalization of the Baldwin-Beckwith rules, which classified the 5-endo-trig radical cyclization as a "disfavored" process.     

Rhenium(I)-induced cyclization of thiosemicarbazones derived from beta-keto esters

The reactions of methylacetoacetate and ethyl 2-methylacetoacetate thiosemicarbazones (H(2)L(A) and H(2)L(B), respectively) with [ReX(CO)(5)] and [ReX(CO)(3)(CH(3)CN)(2)] (X = Cl, Br) were explored under various experimental conditions. Besides the adducts fac-[ReX(CO)(3)(H(2)L)], in which the rhenium is coordinated to three carbonyl groups, the X anion, and the N,S-bidentate thiosemicarbazone ligand, the following complexes were also isolated: fac-[ReBr(CO)(3)(Hpyz(B))], the tetrameric complexes fac-[Re(pyz(A))(CO)(3)](4) and fac-[Re(pyz(B))(CO)(3)](4), and fac-[Re(pyz(B))(CO)(3)(H(2)O)] (where Hpyz(A) and Hpyz(B) are pyrazolones derived by cyclization of H(2)L(A) and H(2)L(B), respectively). The cyclization reactions were monitored by (1)H NMR spectroscopy and the complexes isolated were identified by elemental analysis, mass spectrometry, IR and (1)H NMR spectroscopy, and in some cases by X-ray diffractometry. The isolation and the full structural identification of the rather unusual fac-[ReBr(CO)(3)(Hpyz(B))], which contains the enol form of the pyrazolone ligand, affords new insight into the cyclization of thiosemicarbazones derived from beta-keto esters.     

Metal-induced cyclization of thiosemicarbazones derived from beta-keto amides and beta-keto esters: open-chain and cyclized ligands in zinc(II) complexes

The reactions of Zn(OAc)(2) with acetoacetanilide, methyl acetoacetate, o-acetoacetanisidide, and ethyl 2-methylacetoacetate thiosemicarbazones (HTSC(1), HTSC(2), HTSC(3), and HTSC(4), respectively) were explored in methanol. With HTSC(1), HTSC(2), and HTSC(3), following isolation of the corresponding zinc(II) thiosemicarbazonates [Zn(TSC(x))(2)] (x = 1, 2, 3), the mother liquors afforded pyrazolonate complexes [ZnL(1)(2)(H(2)O)] (HL(1) = 2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothioamide) that had been formed by cyclization of the corresponding TSC(-). The reaction of HTSC(4) with zinc(II) acetate gave only the pyrazolonate complex [ZnL(2)(2)(H(2)O)] (HL(2) = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazole-1-carbothioamide). All compounds were studied by IR and NMR spectroscopy, and HTSC(3), [Zn(TSC(3))(2)] x DMSO, [ZnL(1)(2)(H(2)O)] x 2DMSO, and [ZnL(2)(2)(H(2)O)] x 2DMSO were also studied by X-ray diffractometry, giving a thorough picture of the cyclization process. In preliminary tests of the effects of HL(1) and [ZnL(1)(2)(H(2)O)] on rat paw inflammatory edema induced by carrageenan, HL(1) showed antiinflammatory activity.     

Metal-ligand charge-transfer-promoted photoelectronic Bergman cyclization of copper metalloenediynes: photochemical DNA cleavage via C-4' H-atom abstraction

Metal-to-ligand charge-transfer (MLCT) photolyses (lambda > or = 395 nm) of copper complexes of cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne (bpod, 1), [Cu(bpod)(2)]PF(6) (2), and [Cu(bpod)(2)](NO(3))(2) (3) yield Bergman cyclization of the bound ligands. In contrast, the uncomplexed ligand 1 and Zn(bpod)(2)(CH(3)COO)(2) compound (4) are photochemically inert under the same conditions. In the case of 4, sensitized photochemical generation of the lowest energy (3)pi-pi state, which is localized on the enediyne unit, leads to production of the trans-bpod ligand bound to the Zn(II) cation by photoisomerization. Electrochemical studies show that 1, both the uncomplexed and complexed, exhibits two irreversible waves between E(p) values of -1.75 and -1.93 V (vs SCE), corresponding to reductions of the alkyne units. Irreversible, ligand-based one-electron oxidation waves are also observed at +1.94 and +2.15 V (vs SCE) for 1 and 3. Copper-centered oxidation of 2 and reduction of 3 occur at E(1/2) = +0.15 and +0.38 V, respectively. Combined with the observed Cu(I)-to-pyridine(pi) MLCT and pyridine(pi)-to-Cu(II) ligand-to-metal charge transfer (LMCT) absorption centered near approximately 315 nm, the results suggest a mechanism for photo-Bergman cyclization that is derived from energy transfer to the enediyne unit upon charge-transfer excitation. The intermediates produced upon photolysis degrade both pUC19 bacterial plasmid DNA, as well as a 25-base-pair, double-stranded oligonucleotide. Detailed analyses of the cleavage reactions reveal 5'-phosphate and 3'-phosphoglycolate termini that are derived from H-atom abstraction from the 4'-position of the deoxyribose ring rather than redox-induced base oxidation.     

Model studies of DNA C5' radicals. Selective generation and reactivity of 2'-deoxyadenosin-5'-yl radical

The reaction of hydrated electrons (e(aq)(-)) with 8-bromo-2'-deoxyadenosine has been investigated by radiolytic methods coupled with product studies and addressed computationally by means of DFT-B3LYP calculations. Pulse radiolysis revealed that this reaction was complete in approximately 0.3 mus, and, at this time, no significant absorption was detected. The spectrum of a transient developed in 20 mus has an absorbance in the range 300-500 nm (epsilon(max) congruent with 9600 M(-1) cm(-1) at 360 nm), and it was assigned to aromatic aminyl radical 3. Computed vertical transitions (TD-UB3LYP/6-311+G) are in good agreement with the experimental observations. Radical 3 is obtained by the following reaction sequence: one-electron reductive cleavage of the C-Br bond that gives the C8 radical, a fast radical translocation from the C8 to C5' position, and an intramolecular attack of the C5' radical at the C8,N7 double bond of the adenine moiety. The rate constant for the cyclization is 1.6 x 10(5) s(-1). On the basis of the theoretical findings, the cyclization step is highly stereospecific. The rate constants for the reactions of C5' and aminyl 3 radicals with different oxidants were determined by pulse radiolysis methods. The respective rate constants for the reaction of 2'-deoxyadenosin-5'-yl radical with dioxygen, Fe(CN)(6)(3)(-), and MV(2+) in water at ambient temperature are 1.9 x 10(9), 4.2 x 10(9), and 2.2 x 10(8) M(-1) s(-1). The value for the reaction of aminyl radical 3 with Fe(CN)(6)(3-) is 8.3 x 10(8) M(-1) s(-1), whereas the reaction with dioxygen is reversible. Tailored experiments allowed the reaction mechanism to be defined in some detail. A synthetically useful radical cascade process has also been developed that allows in a one-pot procedure the conversion of 8-bromo-2'-deoxyadenosine to 5',8-cyclo-2'-deoxyadenosine in a diastereoisomeric ratio (5'R):(5'S) = 6:1 and in high yield, by reaction with hydrated electrons in the presence of K(4)Fe(CN)(6).     

Intramolecular hydroamination/cyclization of conjugated aminodienes catalyzed by organolanthanide complexes. Scope, diastereo- and enantioselectivity, and reaction mechanism

Organolanthanide complexes of the general type Cp'(2)LnCH(TMS)(2) (Cp' = eta(5)-Me(5)C(5); Ln = La, Sm, Y; TMS = SiMe(3)) and CGCSmN(TMS)(2) (CGC = Me(2)Si(eta(5)-Me(4)C(5))((t)()BuN)) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization of primary and secondary amines tethered to conjugated dienes. The rates of aminodiene cyclizations are significantly more rapid than those of the corresponding aminoalkenes. This dienyl group rate enhancement as well as substituent group (R) effects on turnover frequencies is consistent with proposed transition state electronic demands. Kinetic and mechanistic data parallel monosubstituted aminoalkene hydroamination/cyclization, with turnover-limiting C=C insertion into the Ln-N bond to presumably form an Ln-eta(3) allyl intermediate, followed by rapid protonolysis of the resulting Ln-C linkage. The rate law is first-order in [catalyst] and zero-order in [aminodiene]. However, depending on the particular substrate and catalyst combination, deviations from zero-order kinetic behavior reflect competitive product inhibition or self-inhibition by substrate. Lanthanide ionic radius effects and ancillary ligation effects on turnover frequencies suggest a sterically more demanding Ln-N insertion step than in aminoalkene cyclohydroamination, while a substantially more negative DeltaS( double dagger ) implies a more highly organized transition state. Good to excellent diastereoselectivity is obtained in the synthesis of 2,5-trans-disubstituted pyrrolidines (80% de) and 2,6-cis-disubstituted piperidines (99% de). Formation of 2-(prop-1-enyl)piperidine using the chiral C(1)-symmetric precatalyst (S)-Me(2)Si(OHF)(CpR)SmN(TMS)(2) (OHF = eta(5)-octahydrofluorenyl; Cp = eta(5)-C(5)H(3); R = (-)-menthyl) proceeds with up to 71% ee. The highly stereoselective feature of aminodiene cyclization is demonstrated by concise syntheses of naturally occurring alkaloids, (+/-)-pinidine and (+)-coniine from simple diene precursors.     

Catalytic asymmetric synthesis of quaternary carbons bearing two aryl substituents. Enantioselective synthesis of 3-alkyl-3-aryl oxindoles by catalytic asymmetric intramolecular heck reactions

A practical sequence involving three consecutive palladium(0)-catalyzed reactions has been developed for synthesizing 3-alkyl-3-aryloxindoles in high enantiopurity. The Heck cyclization precursors 10 and 11a-k are generated in one step by chemoselective Stille cross-coupling of 2'-triflato-(Z)-2-stannyl-2-butenanilide 9 with aryl or heteroaryl iodides. The pivotal catalytic asymmetric Heck cyclization step of this sequence takes place in high yield and with high enantioselectivity (71-98% ee) with the Pd-BINAP catalyst derived from Pd(OAc)(2) to construct oxindoles containing a diaryl-substituted all-carbon quaternary carbon center. A wide variety of aryl and heteroaryl substituents, including ones of considerable steric bulk, can be introduced at C3 of oxindoles in this way (Table 4). The only limitations encountered to date are aryl substituents containing ortho nitro or basic amine functionalities and the bulky N-alkyl-7-oxindolyl group. Asymmetric Heck cyclization of butenalide 22 having an o-(N-acetyl-N-benzylamino)phenyl substituent at C2 provided a approximately 1:1 mixture of amide atropisomers 23 and 24 in high yield and high enantioselectivity. These atropisomers are formed directly upon Heck cyclization of 22 at 80 degrees C, as they interconvert thermally to only a small extent at this temperature.     

Oxidative Prins and Prins/Friedel-Crafts cyclizations for the stereoselective synthesis of dioxabicycles and hexahydro-1H-benzo[f]isochromenes via the benzylic C-H activation

1-Benzyl ethers of (E)- and (Z)-hex-3-en-1,6-diols and hept-3-en-1,7-diols undergo a smooth oxidative cyclization with DDQ in the presence of In(OTf)(3) through a sequential C-H bond activation and an intramolecular Prins cyclization to afford the corresponding trans- and cis-fused hexahydro-2H-furo[3,2-c]pyrans and octahydropyrano[4,3-b]pyrans respectively in good yields with an excellent stereoselectivity. Aryl tethered homoallylbenzyl ethers such as benzyl ethers of (E)- and (Z)-6-arylhex-3-enyl alcohols undergo a tandem Prins/Friedel-Crafts cyclization in the presence of stoichiometric amounts of DDQ and SnCl(4)via the benzylic C-H bond activation to furnish the corresponding trans- and cis-fused hexahydro-1H-benzo[f]isochromenes in good yields with complete stereoselectivity.     

Rhodium-catalyzed asymmetric cyclization/hydroboration of 1,6-enynes

[reaction: see text] Reaction of enyne 1 with catecholborane catalyzed by a 1:1 mixture of [Rh(COD)(2)](+)SbF(6)(-) and (S)-BINAP (5 mol %) followed by Pd-catalyzed arylation with p-IC(6)H(4)CF(3) gave benzylidenecyclopentane 5 in 65% yield with 88% ee. Rhodium-catalyzed asymmetric cyclization/hydroboration followed either by Pd-catalyzed arylation or by oxidation was applied to the synthesis of a number of chiral, nonracemic carbocycles and heterocycles.     

Sulfate radical anions (SO(4)(*)(-)) as donor of atomic oxygen in anionic transannular, self-terminating, oxidative radical cyclizations

SO(4)(*)(-) generated by the Fenton redox system S(2)O(8)(2)(-)- Fe(2+) induces a novel anionic, transannular, self-terminating, oxidative radical cyclization in the reactions with the ten-membered cycloalkyne 1 and the cycloalkynone 7, yielding the bicyclic ketones 5 and 6 or the alpha,beta-epoxy ketones 8 and 9, respectively. In these reactions SO(4)(*)(-) acts as an oxygen transfer reagent and can thus be considered as a donor of atomic oxygen in solution.