Imino ene reaction catalyzed by ytterbium(III) triflate and TMSCl or TMSOTf

A novel combined system of Yb(OTf)(3) with TMSCl or TMSOTf catalyzed an imino ene reaction. The reaction of N-tosylbenzaldimine (1) with alpha-methylstyrene (2) proceeded smoothly to give homoallylic amine 3 in the presence of a catalytic amount of Yb(OTf)(3) and TMSCl. This catalytic system was successfully applied to the imino ene reactions of various aldimines with alkenes. This new imino ene reaction provides a unique method for the three-component coupling reaction of an aldehyde, tosylamide, and alpha-methylstyrene in the presence of Yb(OTf)(3) and TMSOTf, to give the corresponding homoallylic amine.     

An efficient and mild bismuth triflate-catalysed three-component Mannich-type reaction

In the presence of a catalytic amount of Bi(OTf)(3).4H(2)O, aldehydes together with amines react with silyl enolates to afford the corresponding Mannich-type adducts smoothly. A wide variety of silyl enolates derived from ketones, as well as esters and thioesters, react rapidly to afford the beta-amino ketones or the beta-amino esters in high yields (up to 94%).     

Stereoblock copolymers and tacticity control in controlled/living radical polymerization

Three controlled/living radical polymerization processes, atom transfer radical polymerization (ATRP), reversible addition-fragmentation transfer (RAFT) polymerization, and nitroxide-mediated polymerization (NMP), were investigated for the polymerization of N,N-dimethylacrylamide in the presence of Lewis acids known to enhance isotacticity, such as yttrium trifluoromethanesulfonate (Y(OTf)(3)) and ytterbium trifluoromethanesulfonate (Yb(OTf)(3)). Poly(N,N-dimethylacrylamide) with controlled molecular weight, low polydispersity (M(w)/M(n) < 1.2), and a high proportion of meso dyads ( approximately 85%) was prepared by ATRP (with initiating system methyl 2-chloropropionate/CuCl/Me(6)TREN) and RAFT (with cumyl dithiobenzoate transfer agent) in the presence of Y(OTf)(3). The combination of NMP (using N-tert-butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide, SG1) and a Lewis acid complexation technique led to less precise control over chain architecture and microstructure ( approximately 65% meso dyads), as compared to RAFT/Y(OTf)(3) or ATRP/Y(OTf)(3). The latter two systems were used for the first one-pot synthesis of stereoblock copolymers by radical polymerization. Well-defined stereoblock copolymers, atactic-b-isotactic poly(N,N-dimethylacrylamides), were obtained by adding Y(OTf)(3) at a given time to either RAFT or ATRP polymerizations, initially started without the presence of the Lewis acid.     

Scandium ion-promoted photoinduced electron transfer from electron donors to acridine and pyrene. Essential role of scandium ion in photocatalytic oxygenation of hexamethylbenzene

Photoinduced electron transfer from a variety of electron donors including alkylbenzenes to the singlet excited state of acridine and pyrene is accelerated significantly by the presence of scandium triflate [Sc(OTf)(3)] in acetonitrile, whereas no photoinduced electron transfer from alkylbenzenes to the singlet excited state of acridine or pyrene takes place in the absence of Sc(OTf)(3). The rate constants of the Sc(OTf)(3)-promoted photoinduced electron-transfer reactions (k(et)) of acridine to afford the complex between acridine radical anion and Sc(OTf)(3) remain constant under the conditions such that all the acridine molecules form the complex with Sc(OTf)(3). In contrast to the case of acridine, the k(et) value of the Sc(OTf)(3)-promoted photoinduced electron transfer of pyrene increases with an increase in concentration of Sc(OTf)(3) to exhibit first-order dependence on [Sc(OTf)(3)] at low concentrations, changing to second-order dependence at high concentrations. The first-order and second-order dependence of k(et) on [Sc(OTf)(3)] is ascribed to the 1:1 and 1:2 complexes formation between pyrene radical anion and Sc(OTf)(3). The positive shifts of the one-electron redox potentials for the couple between the singlet excited state and the ground-state radical anion of acridine and pyrene in the presence of Sc(OTf)(3) as compared to those in the absence of Sc(OTf)(3) have been determined by adapting the free energy relationship for the photoinduced electron-transfer reactions. The Sc(OTf)(3)-promoted photoinduced electron transfer from hexamethylbenzene to the singlet excited state of acridine or pyrene leads to efficient oxygenation of hexamethylbenzene to produce pentamethylbenzyl alcohol which is further oxygenated under prolonged photoirradiation of an O(2)-saturated acetonitrile solution of hexamethylbenzene in the presence of acridine or pyrene which acts as a photocatalyst together with Sc(OTf)(3). The photocatalytic oxygenation mechanism has been proposed based on the studies on the quantum yields, the fluorescence quenching, and direct detection of the reaction intermediates by ESR and laser flash photolysis.     

Synthesis and chiral recognition ability of optically active poly{N‐[(R)‐α‐methoxycarbonylbenzyl]methacrylamide} with various tacticities by radical polymerization using Lewis acids

The radical polymerization of an optically active methacrylamide, N‐[(R)‐α‐methoxycarbonylbenzyl]methacrylamide, was carried out in the absence and presence of Lewis acids such as yittribium trifluoromethanesulfonate [Yb(OTf)₃] and scandium trifluoromethanesulfonate [Sc(OTf)₃]. Catalytic amounts of the Lewis acids significantly affected the stereoregularity of the obtained polymers. The polymerization with Yb(OTf)₃ in tetrahydrofuran afforded isotactic polymers (up to mm = 87%), whereas the conventional radical method without the Lewis acid produced polymers rich in syndiotacticity (up to rr = 88%). The radical polymerization in the presence of MgBr₂ proceeded in a heterotactic‐selective manner (mr = 63%). Thus, the isotactic, syndiotactic, and heterotactic poly(methacrylamide)s were synthesized by the radical processes. The chiral recognition abilities of the obtained optically active poly(methacrylamide)s were affected by the stereoregularity. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3354–3360, 2003     

Adamantylation of β-dicarbonyl compounds

Reactions of adamantan-1-ol with β-dicarbonyl compounds in 1,2-dichloroethane in the presence of In(OTf)₃, Ga(OTf)₃, Sc(OTf)₃, or Cu(OTf)₂ give the corresponding adamantylated derivatives in 45–93% yields.     

Elusive 6-exo-Hydroxybicyclo[2.2.2]octan-2-ones from the corresponding acetates by methanolysis in the presence of CH(3)ONa/La(OTf)(3)

[reaction: see text] A series of 6-exo-acetoxybicyclo[2.2.2]octan-2-ones were converted into the corresponding 6-exo-hydroxybicyclo[2.2.2]octan-2-ones by methanolysis in the presence of CH(3)ONa/La(OTf)(3). Under the given conditions, epimerization at C(6) of the latter led in the least favorable cases only to traces of the more stable 6-endo-hydroxybicyclo[2.2.2]octan-2-ones. This procedure, when combined with the described conversion of easily available 6-endo-hydroxybicyclo[2.2.2]octan-2-ones into the corresponding 6-exo-acetoxy derivatives, provides a convenient route to elusive 6-exo-hydroxybicyclo[2.2.2]octan-2-ones. Applications to total synthesis are shown and envisaged.     

Convergent total synthesis of (+)-mycalamide A

The details of a convergent total synthesis of (+)-mycalamide A are described. Yb(OTf)3-TMSCl-catalyzed cross-aldol reaction conditions are used to synthesize the right segment of mycalamide A. In this reaction, an acid-sensitive aldehyde reacts with methyl trimethylsilyl dimethylketene acetal without epimerization to provide the desired aldol adduct. Additionally, a tetrahydropyran ring, which is the left segment of mycalamide A, is prepared using a novel one-pot delta-lactone formation methodology. Both segments are constructed from a common starting material, d-mannitol. These segments are then coupled in the presence of BuLi, and the functional groups are transformed to complete the synthesis of (+)-mycalamide A.     

Stereoselective pinacol coupling of chiral formylferrocene using divalent samarium triflate: preparation of a new chiral bisferrocenyl oxazoline ligand and its application to asymmetric Diels-Alder reactions

[reaction: see text] The pinacol coupling reaction of planar chiral ortho-oxazoline-substituted formylferrocene was smoothly mediated by SmI2 or Sm(OTf)3 to give the (R,R) isomer selectivity (up to 76% diastereomeric excess). The combination of Yb(OTf)3 and the (R,R)-ferrocenyl diol was revealed to be a good catalyst for the asymmetric Diels-Alder reaction of 3-acyloxazolidinone with cyclopentadiene, and the endo adduct was produced in up to 80% enantiomeric excess.     

Improved synthesis of functional CTVs and cryptophanes using Sc(OTf)3 as catalyst

Functional cyclotriveratrylene (CTV) and cryptophane derivatives are synthesized in the presence of scandium triflate [Sc(OTf)3]. This route allows the preparation of new derivatives that could not be prepared or easily obtained by using the previously reported experimental procedures. With a catalytic amount of scandium triflate (1% mol), CTVs were obtained with yields similar to or higher than those reported previously in reactions run under strong acidic conditions. Cryptophanes were also synthesized in fairly good yields by performing the ring-closure step in the presence of a stoichiometric amount of Sc(OTf)3. Interestingly, this novel approach strongly reduces the formation of side products and gives rise to novel functionalized molecules for the construction of supramolecular host-guest systems.     

An Asymmetric, bifunctional catalytic approach to non-natural alpha-amino acid derivatives

A catalytic, asymmetric process for the synthesis of 1,4-benzoxazinones from o-benzoquinone imides and ketene enolates is reported. Addition of Lewis acids (Zn(OTf)2, In(OTf)3, and in particular Sc(OTf)3) creates a bifunctional catalytic system that dramatically increases the reaction rate and the yield of these non-natural amino acid precursors while preserving the remarkable enantioselectivity inherent to the reaction. Cocatalyst Sc(OTf)3 increases the yield by up to 42% while producing products in >99% ee.     

Indium-mediated asymmetric Barbier-type propargylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents

We report a simple, efficient, and general method for the indium-mediated enantioselective propargylation of aromatic and aliphatic aldehydes under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 90%) and enantiomeric excess (up to 95%). The extension of this methodology to ketones demonstrated the need for electrophilic ketones more reactive than acetophenone as the reaction would not proceed with just acetophenone. Using the Lewis acid indium triflate [In(OTf)(3)] induced regioselective formation of the corresponding homoallenic alcohol product from acetophenone. However, this methodology demonstrated excellent chemoselectivity in formation of only the corresponding secondary homopropargylic alcohol product in the presence of a ketone functionality. Investigation of the organoindium intermediates under our reaction conditions shows the formation of allenylindium species, and we suggest that these species contain an indium(III) center. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.     

Total synthesis of pteridic acids A and B

Pteridic acid A (1) is a spirocyclic octaketide produced by the phytoepiphytic actinomycete Streptomyces hygroscopicus TP-A0451 and possesses potent plant-growth-promoting activity comparable to that of indole-3-acetic acid. The enantioselective total synthesis of this natural product was achieved by employing the Sn(OTf)(2)-mediated Evans aldol reaction and the Fukuyama acetylenic coupling reaction as the key C--C bond-forming steps producing 1 through a 14-step sequence in 22 % overall yield from a known oxazolidinone derivative. MgBr(2)-mediated equilibration of an anomerically favored spirocyclic intermediate used for the synthesis of 1 brought about partial epimerization of the spirocenter to give the corresponding anomerically disfavored epimer, which was converted into pteridic acid B (11-epi-1), another plant-growth promoter of the same microbial origin.     

Facile synthesis of 3,5-diaryl-1,2,4-triazoles via copper-catalyzed domino nucleophilic substitution/oxidative cyclization using amidines or imidates as substrates

Two methods for the synthesis of 3,5-diaryl-1,2,4-triazoles, both domino reactions, are reported. The first procedure, the Cu(OTf)₂-catalyzed reaction between two amidines using NaHCO₃ as a base, 1,10-phenanthroline as an additive and K₃[Fe(CN)₆]/atmospheric oxygen as the oxidant, delivers 3,5-diaryl-1,2,4-triazoles with yields up to 68%. The second procedure for the synthesis of 3,5-diaryl-1,2,4-triazoles with yields up to 64% rests on the Cu(OTf)₂-catalyzed reaction between two imidates and ammonium carbonate. This method features the formation of three bonds in a single synthetic step.     

Polymer-supported glyoxylate and alpha-imino acetates. Versatile reagents for the synthesis of alpha-hydroxycarboxylic acid and alpha-amino acid libraries

Polymer-supported glyoxylate.monohydrate (3) and alpha-imino acetates (7) have been readily prepared from chloromethylated resin via two or three steps. The ene reactions of 3 with alkenes were successfully performed in the presence of Yb(OTf)3 (50 mol %) to afford, after cleavage from the polymer support, the corresponding alpha-hydroxycarboxylic acid esters in good yields. The reactions of 7 with silyl enolates, Danishefsky's diene, and alkenes also proceeded smoothly in the presence of Sc(OTf)3 (20 mol %) to give the corresponding alpha-amino acid, pyridone, and tetrahydroquinoline derivatives, respectively, in good yields.     

Enol esters: versatile substrates for Mannich-type multicomponent reactions

The interaction of cyclic enol esters with diversely substituted anilines and ethyl glyoxalate yields, under Sc(OTf)3 catalysis, disubstituted N-aryl lactams in a multicomponent reaction. The protocol allows access to the trans stereoisomers after an epimerization of the initial mixture in which the cis isomers predominate. Vinyl acetate yields quinoline derivatives, whereas isopropenyl acetate leads to the corresponding Mannich adducts.     

Cyclopropane-aldehyde annulations at quaternary donor sites: stereoselective access to highly substituted tetrahydrofurans

A diastereoselective synthesis of pentasubstituted tetrahydrofurans via a Lewis acid catalyzed (3 + 2)-annulation of quaternary donor site cyclopropanes and aldehydes is described. The reaction is catalyzed by Sn(OTf)(2), SnCl(4), or Hf(OTf)(4) in yields up to 95% and diastereomeric ratios as high as 99:1.     

简单亚胺的高效烯丙基化反应研究

首次实现了In(OTf)3催化下二丁基二烯丙基锡对活性较低的简单亚胺的高效烯丙基化加成. 烯丙基锡试剂和亚胺底物在10 mol%的In(OTf)3催化下, 无需添加其它辅助试剂, 二氯甲烷中室温搅拌10 h, 就可以得到收率为80%～99%的高烯丙基胺产物. 用四烯丙基锡替换该体系中的二丁基二烯丙基锡, 50 mol%用量即能得到很好的结果. 同时还对反应的机理进行了探讨.     

Group 3 metal (Sc, La) triflates as catalysts for the carbomethoxylation of aliphatic amines with dimethylcarbonate under mild conditions

The activity of Sc(OTf)₃ and La(OTf)₃ (OTf=SO₃CF₃) as catalysts for the phosgene-free synthesis of carbamate esters via carbomethoxylation of aliphatic amines with dimethylcarbonate (DMC) has been investigated. In the presence of M(OTf)₃ (M=Sc, La), primary and secondary aliphatic amines easily react with dimethylcarbonate, under very mild conditions (20 °C), to afford carbamate esters with good yield and excellent selectivity (≌100%). Sc(OTf)₃ is a more effective catalyst than the homologue La salt. The carbomethoxylation reaction requires as strict anhydrous conditions, as, at 20 °C, the presence of water inhibits markedly the catalytic activity of both triflate salts. Temperature influences carbamate selectivity, which is lower at higher temperature because of deleterious formation of N-methylation side-products.     

New entries to water-compatible Lewis acids

Lewis acid catalysis has attracted much attention in organic synthesis as it often affords access to unique reactivity and selectivity under mild conditions. Although various kinds of Lewis acids have been developed and applied in industry, these Lewis acids must be generally used under strictly anhydrous conditions, as the presence of even a small amount of water interferes with the reactions due to preferential reaction of the Lewis acids with water rather than the substrates. In contrast to this, rare earth and other metal complexes have been found to be water-compatible. Furthermore, Bi(OTf)(3)- and Ga(OTf)(3)-basic ligand complexes have also been found to be stable in water, and have been used as water-compatible Lewis acids. This application is particularly significant, as Bi(OTf)(3) and Ga(OTf)(3) themselves are unstable in the presence of water, but are stabilized by the basic ligands. This observation has led to the development of a new approach to Lewis acid catalysis in which Lewis acids that are generally unstable in the presence of water are rendered amenable to aqueous systems when combined with basic ligands. In particular, the use of chiral basic ligands leading to new types of water-compatible chiral Lewis acids may enable a wide range of asymmetric catalysis in aqueous media.