Catalyst-Controlled, Enantioselective, and Diastereodivergent Conjugate Addition of Aldehydes to Electron-Deficient Olefins.

A chiral-amine-catalyzed enantioselective and diastereodivergent method for aldehyde addition to electron-deficient olefins is presented. Hydrogen bonding was used as a control element to achieve unusual anti selectivity, which was further elucidated through mechanistic and computational studies.

Design of a New Bimetallic Catalyst for Asymmetric Epoxidation and Sulfoxidation.

A new chiral tethered 8-quinolinol-based ligand class is developed. The binuclear titanium complex of the ligand operates through a novel mechanism allowing for the regio- and stereoselective epoxidation of primary and tertiary homoallylic alcohols (up to 98% ee), as well as first examples of 2-allylic phenols (up to 92% ee). The new catalyst system also promotes the asymmetric oxidation of γ-hydroxypropyl sulfides giving an important class of chiral sulfoxides that have been inaccessible to date (up to 95% ee).

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.

Chemoselective silyl transfer in the Mukaiyama aldol reaction promoted by super silyl Lewis acid.

In the silyl Lewis acid-promoted Mukaiyama aldol reaction, the steric and electronic properties of the silyl group on the silyl Lewis acid influence the reaction mechanism and product distribution. When super silyl triflates such as (TMS)3SiOTf and (TES)3SiOTf are used as Lewis acids, the silyl group of the silyl enol ether chemoselectively transfers to the product. The mechanistic details have been investigated using density functional theory (DFT) calculations.

An enantioselective Diels-Alder reaction of 1,2-dihydropyridines with α-acyloxyacroleins catalyzed by a chiral primary ammonium salt.

The first enantioselective Diels-Alder reaction of 1,2-dihydropyridines with α-acyloxyacroleins catalyzed by a chiral primary ammonium salt has been developed and it offers more efficient routes to key synthetic intermediates of alkaloids, for which the direct preparations were unavailable before. The asymmetric induction can be understood through the optimized geometry of an iminium salt aqua complex derived from the catalyst and the dienophile.

Selective bromocyclization of 2-geranylphenols promoted by phosphite-urea cooperative catalysts.

Nucleophilic phosphite-urea cooperative catalysts are highly efficient for the bromonium-induced cyclization of 2-geranylphenols. Phosphite-N,N'-dimethylurea catalysts also show moderate activity, probably due to the steric effect of their bent conformation.

Powerful amino diol catalyst for effecting the direct asymmetric conjugate addition of aldehydes to acrylates.

Di-tert-butyl methylenemalonate (1) could be employed as a reactive equivalent of a three-carbon Michael acceptor such as acrylate in a direct asymmetric conjugate addition of aldehydes catalyzed by an axially chiral amino diol (S)-3a. Furthermore, acrylate, an unexplored and challenging substrate in enamine catalysis, has also been successfully employed in asymmetric conjugate addition reaction. Relatively inert acrylate is doubly activated by polyfluoroalkyl group of 2 and the hydroxyl group on the axially chiral amino diol catalyst (S)-3b, giving corresponding conjugate adducts in high yield with excellent enantiomeric excess. The obtained conjugate addition products were readily converted to synthetically useful and important chiral building blocks.

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.

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.

Rapid, one-pot synthesis of ß-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-ß-siloxy-α-haloaldehydes. A highly diastereoselective, one-pot, sequential double-aldol process is developed, affording novel ß,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.

Rational design of highly effective asymmetric Diels-Alder catalysts bearing 4,4'-sulfonamidomethyl groups.

The rational design of bis(oxazoline)-copper(II) catalysts based on postulated intramolecular secondary n-cation interaction for the highly enantioselective Diels-Alder reaction is presented. A theoretical calculation suggested that the n electrons of the 4,4'-sulfonamidomethyl groups successfully interact with the Cu(II) cation and that the counteranions with protons of sulfonamido groups. These secondary interactions might be essential for the high catalytic activity, the broad range of substrates, and the high level of induction of the enantioselectivity.

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.

Organocatalytic enantioselective Diels-Alder reaction of dienes with alpha-(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.