Lewis base catalyzed Mannich-type reactions between trimethylsilyl enol ethers and aldimines

Lewis base catalyzed Mannich-type reaction between trimethylsilyl enol ethers and N-tosylaldimines is described. Nitrogen anions generated from amides or imides such as lithium benzamide or potassium phthalimide are found to be effective Lewis base catalysts in DMF at room temperature to afford the corresponding beta-amino carbonyl compounds in good to high yields; the oxygen anion generated from carboxylic acids such as lithium acetate was also found to be effective in dry DMF. The above-mentioned lithium acetate-catalyzed Mannich-type reaction between aldimines and various trimethylsilyl (TMS) enol ethers such as silyl ketene acetal proceeded smoothly even in water-containing DMF. Then, Lewis base catalyzed three-component Mannich-type reactions of TMS enol ether, tosylamide, and aromatic aldehyde having electron-withdrawing group such as p-nitrobenzaldehyde were investigated. The reaction proceeded smoothly to afford the corresponding beta-amino ester in good yield. Further, ammonium carboxylates such as tetrabutyl ammonium acetate or tetrabutyl ammonium benzoate were found to be more effective Lewis base catalysts in the above-mentioned Mannich-type reaction. The synthesis proceeded in various solvents at lower temperatures. The reaction between aldimines and TMS enol ethers generated from thioester and various ketones such as propiophenone or cyclohexanone also proceeded smoothly to afford the corresponding beta-amino carbonyl compounds in high yields with good to high anti-selectivities.     

Lewis acid-catalyzed Prins-type reactions of methylenecyclopropylcarbinols with aldehydes and aldimines

Lewis acid-catalyzed Prins-type reactions of methylenecyclopropylcarbinols with aldehydes and aldimines proceeded smoothly to give the corresponding 3-oxa-bicyclo[3.1.0]hexane units via 5-exo cyclization in good to high total yields.     

Highly regioselective palladium/copper-catalysed cross-coupling reactions of terminal alkynes and allenes

The Pd/Cu-catalysed cross-coupling reaction of heterocyclic terminal alkynes and allene/allenyl heterocycles affords novel trisubstituted en-ynes in good yield.     

Novel amine-catalysed hydroalkoxylation reactions of activated alkenes and alkynes

Substoichiometric loadings of DBU catalyse the efficient 1,4-addition of alcohols and non-nucleophilic amines such as pyrrole to activated alkenes; the application of this methodology in a one-pot synthesis of a natural product, and as a novel strategy for the synthesis of mono-protected 1,3-carbonyl compounds is reported.     

Lewis acid promoted Mannich type reactions of α,α-dichloro aldimines with potassium organotrifluoroborates

Potassium phenylethynyltrifluoroborate and potassium styryltrifluoroborates react with α,α-dichlorinated aldimines in the presence of BF₃·OEt₂ as a Lewis acid to give a new stable class of functionalized propargylamines and allylamines. The use of hexafluoroisopropanol as a co-solvent in this modified Petasis reaction allows high yield isolation of the target compounds.     

Lewis base activation of Lewis acids. Vinylogous aldol reactions

A highly regioselective vinylogous aldol reaction catalyzed by SiCl4 and a chiral phosphoramide (R,R)-5, providing delta-hydroxy enones for a variety of aldehyde and dienol ether structures, has been developed. Low catalyst loadings (1 mol %) can be employed, giving the products in good yields, excellent enantioselectivities, and in some cases excellent anti diastereoselectivities. Both simple ester-derived dienol ethers as well as dioxanone-derived dienol ethers are employed. The observed regioselectivity is rationalized in terms of the sensitivity of the catalyst to the steric demands of the nucleophile.     

Aza-Baylis-Hillman reactions of diisopropyl azodicarboxylate or diethyl azodicarboxylate with acrylates and acrylonitrile

It has been found that in the Baylis-Hillman reactions of DIAD or DEAD with acrylates or acrylonitrile, the Lewis base and solvent can significantly affect the reaction rate. Using DABCO as Lewis base in DMF or THF, the corresponding aza-Baylis-Hillman adducts 2 or 3 can be obtained in moderate to good yields.     

Polymerization of acrylamide in various solvents in the presence of Lewis acids

The radical polymerization of acrylamide in various solvents in the presence of Lewis acids has been investigated. Considerable effects of LiBr, LiCl and CaCl₂ on the total reaction rate and the values of k_p and k₁ for polymerization in DMSO or THF have been shown. For the polymerization of acrylamide in aqueous solution, addition of the salts does not affect the kinetic behaviour of the process. The observed effect of salts arises from complexation between the salt and the monomer and/or the propagating radicals.     

Catalytic asymmetric Mannich-type reactions of fluorinated ketoesters with N-Boc aldimines in the presence of chiral palladium complexes

The catalytic enantioselective Mannich reaction promoted by chiral palladium complexes is described. The treatment of α-fluoro-β-ketoesters with N-Boc-aldimines under mild reaction conditions afforded the corresponding β-aminated α-fluoro-β-ketoesters with excellent enantioselectivities (up to 99% ee).     

Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions

The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.     

Different N-C-N formation reactions of aromatic aldehydes and thiohydantoins controlled by Lewis acid promoters

A three-component reaction of aromatic aldehydes, acetonitrile, and 2-thiohydantoins promoted by TiCl₄ was discovered, and a different N-C-N bond-forming reaction took place with FeCl₃, AlCl₃ or BF₃·Et₂O as promoter. The thiohydantoin derivatives 1 and 3 were synthesized in moderate to high yields. A plausible mechanism for the formation of 1 and 3 is suggested.     

Thermally activated chemical reactions in the presence of internal multiplicative noise

The rate of escape over the barrier of a double-well potential is estimated for the Lindenberg—Seshadri model, both in the overdamped and underdamped Limit. The internal multiplicative noise terms are shown analytically to play distinct roles in the two regimes so that these cannot be assimilated to an “effective” friction for application purposes.     

The development of new monometallic bifunctional catalysts with Lewis acid and Lewis base properties, and their application in asymmetric cyanation reactions

Bifunctional catalysts can drastically improve the efficiency of asymmetric processes with respect to enantioselectivity and/or conversion rate. A new type of chiral bifunctional catalyst has been developed recently in the Shibasaki group that contains both Lewis acid and Lewis base moieties. These monometallic and bifunctional phosphinoyl-containing catalysts are able to coordinate both nucleophilic and electrophilic substrates in the transition state. Several successful applications of this new catalytic concept in the field of asymmetric cyanation reactions have already been reported, for example, the asymmetric hydrocyanation of aldehydes and imines as well as the asymmetric Reissert reaction. The development and principle of this catalytic concept as well as main applications thereof are reviewed in this article.     

Lewis acid catalyzed ring-opening reactions of methylenecyclopropanes with diphenylphosphine oxide in the presence of sulfur or selenium

Methylenecyclopropanes undergo an interesting Lewis acid-catalyzed ring-opening reaction with diphenylphosphine oxide in the presence of sulfur or selenium upon heating at 85 degrees C in 1,2-dichloroethane to give the corresponding homoallylic thiol or selenol derivatives in good to high yields.