Matsujiro Akakura

2-Iodoxybenzenesulfonic Acid as an Extremely Active Catalyst for the Selective Oxidation of Alcohols to Aldehydes, Ketones, Carboxylic Acids, and Enones with Oxone

Electron-donating group-substituted 2-iodoxybenzoic acids (IBXs) such as 5-Me-IBX (1g), 5-MeO-IBX (1h), and 4,5-Me(2)-IBX (1i) were superior to IBX 1a as catalysts for the oxidation of alcohols with Oxone (a trademark of DuPont) under nonaqueous conditions, although Oxone was almost insoluble in most organic solvents. The catalytic oxidation proceeded more rapidly and cleanly in nitromethane. Furthermore, 2-iodoxybenzenesulfonic acid (IBS, 6a) was much more active than modified IBXs. Thus, we established a highly efficient and selective method for the oxidation of primary and secondary alcohols to carbonyl compounds such as aldehydes, carboxylic acids, and ketones with Oxone in nonaqueous nitromethane, acetonitrile, or ethyl acetate in the presence of 0.05-5 mol % of 6a, which was generated in situ from 2-iodobenzenesulfonic acid (7a) or its sodium salt. Cycloalkanones could be further oxidized to alpha,beta-cycloalkenones or lactones by controlling the amounts of Oxone under the same conditions as above. When Oxone was used under nonaqueous conditions, Oxone wastes could be removed by simple filtration. Based on theoretical calculations, we considered that the relatively ionic character of the intramolecular hypervalent iodine-OSO(2) bond of IBS might lower the twisting barrier of the alkoxyperiodinane intermediate 16.

Stereocontrolled Synthesis of Vicinal Diamines by Organocatalytic Asymmetric Mannich Reaction of N-Protected Aminoacetaldehydes: Formal Synthesis of (−)-Agelastatin A

The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both syn- and anti-selective asymmetric direct Mannich reactions of N-protected aminoacetaldehydes with N-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (S)-3. This organocatalytic process represents the first example of a Mannich reaction using Z- or Boc-protected aminoacetaldehyde as a new entry of α-nitrogen functionalized aldehyde nucleophile in enamine catalysis. The obtained optically active vicinal diamines are useful chiral synthons as exemplified by the formal synthesis of (-)-agelastatin A.

Organocatalytic Enantioselective Diels−Alder Reaction of Dienes with α-(N,N-Diacylamino)acroleins

Catalytic and highly enantioselective Diels-Alder reaction of cyclic and acyclic dienes with alpha-phthalimidoacroleins provides cyclic alpha-quaternary alpha-amino acid precursors. The conformationally flexible chiral ammonium salt of H-L-Phe-L-Leu-N(CH(2)CH(2)) 2-reduced triamine with pentafluorobenzensulfonic acid is very effective as an asymmetric catalyst for the Diels-Alder reaction.

Rapid, one-pot synthesis of β-siloxy-α-haloaldehydes.

The Mukaiyama cross-aldol reaction of α-fluoro-, α-chloro-, and α-bromoacetaldehyde-derived (Z)-tris(trimethylsilyl)silyl enol ethers is described, furnishing anti-β-siloxy-α-haloaldehydes. A highly diastereoselective, one-pot, sequential double-aldol process is developed, affording novel β,δ-bissiloxy-α,γ-bishaloaldehydes. Reactions are catalyzed by C(6)F(5)CHTf(2) and C(6)F(5)CTf(2)AlMe(2) (0.5-1.5 mol %) and provide access to halogenated polyketide fragments.

Brønsted Base-Assisted Boronic Acid Catalysis for the Dehydrative Intramolecular Condensation of Dicarboxylic Acids

Brønsted base-assisted boronic acid catalysis for the dehydrative self-condensation of carboxylic acids is described. Arylboronic acid bearing bulky (N,N-dialkylamino)methyl groups at the 2,6-positions can catalyze the intramolecular dehydrative condensation of di- and tetracarboxylic acids. This is the first successful method for the catalytic dehydrative self-condensation of carboxylic acids.

Ketone Super Silyl Enol Ethers in Sequential Reactions: Diastereoselective Generation of Tertiary Carbinols in One Pot

Ketone super silyl enol ethers are shown to be excellent nucleophiles in the Mukaiyama aldol reaction as well as in sequential one-pot diastereoselective reactions. High yields and diastereoselectivities are obtained with a variety of silyl enol ether/aldehyde/Grignard combinations. The utility of this reaction is exemplified in a one-pot 4-component reaction generating two secondary and one tertiary alcohol in one step.

Hydrophobic N,N-Diarylammonium Pyrosulfates as Dehydrative Condensation Catalysts under Aqueous Conditions

Oil-soluble N,N-diarylammonium pyrosulfates as nonsurfactant-type catalysts for the dehydrative ester condensation under aqueous conditions are described. Preheat treatment of dibasic sulfuric acid with bulky N,N-diarylamines generates water-tolerant salts of pyrosulfuric acid as active catalyst species. The present catalysts in water can also widely be applied to unusual selective esterifications and dehydrative glycosylation.

Boron Tribromide-Assisted Chiral Phosphoric Acid Catalyst for a Highly Enantioselective Diels–Alder Reaction of 1,2-Dihydropyridines

BBr3-chiral phosphoric acid complexes are highly effective and practical Lewis acid-assisted Brønsted acid (LBA) catalysts for promoting the enantioselective Diels-Alder (DA) reaction of α-substituted acroleins and α-CF3 acrylate. In particular, the DA reaction of α-substituted acroleins with 1,2-dihydropyridines gave the corresponding optically active isoquinuclidines with high enantioselectivities. Moreover, transformations to the key intermediates of indole alkaloids, catharanthine and allocatharanthine, are demonstrated.

Intramolecular Dehydrative Condensation of Dicarboxylic Acids with Brønsted Base-Assisted Boronic Acid Catalysts

Bifunctional Bronsted base-assisted boronic acid catalysts, arylboronic acids bearing two sterically bulky (N,N-dialkylamino)methyl groups at the 2,6-positions, exhibit remarkable activities for the dehydrative intramolecular condensation of dicarboxylic acids. The steric bulkiness of the (N,N-dialkylamino)methyl groups of 1, which prevents the formation of less active species such as the N→B chelated species and triarylboroxines 3, is crucial for the high catalytic activity. This is the first successful method for the catalytic dehydrative self-condensation of di- and tetracarboxylic acids.

Controlling stereochemistry in polyketide synthesis: 1,3- vs. 1,2-asymmetric induction in methyl ketone aldol additions to β-super siloxy aldehydes

The aldol addition of methyl ketones to β-siloxy and α-methyl β-siloxy aldehydes is described. Careful control of mechanistically distinct aldol reactions leverages 1,2- and 1,3-asymmetric induction, selectively forming syn and anti aldol adducts with excellent diastereocontrol. Experimental and theoretical investigations have provided insight to the factors governing diastereoselectivity.