José R. Pedro

New Highly Asymmetric Henry Reaction Catalyzed by CuII and a C1‐Symmetric Aminopyridine Ligand, and Its Application to the Synthesis of Miconazole

A new catalytic asymmetric Henry reaction has been developed that uses a C(1)-symmetric chiral aminopyridine ligand derived from camphor and picolylamine. A variety of aromatic, heteroaromatic, aliphatic, and unsaturated aldehydes react with nitromethane and other nitroalkanes in the presence of DIPEA (1.0 equiv), Cu(OAc)(2)*H(2)O (5 mol %), and an aminopyridine ligand (5 mol %) to give the expected products in high yields (up to 99 %), moderate-to-good diastereoselectivites (up to 82:18), and excellent enantioselectivities (up to 98 %). The reaction is air-tolerant and has been used in the synthesis of the antifungal agent miconazole.

Organocatalytic Asymmetric Addition of Naphthols and Electron‐Rich Phenols to Isatin‐Derived Ketimines: Highly Enantioselective Construction of Tetrasubstituted Stereocenters

A quinine-derived thiourea organocatalyst promoted the highly enantioselective addition of naphthols and activated phenols to ketimines derived from isatins. The reaction afforded chiral 3-amino-2-oxindoles with a quaternary stereocenter in high yields (up to 99%) with excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this transformation is the first highly enantioselective addition of naphthols to ketimines.

Highly Enantioselective Zinc/Binol‐Catalyzed Alkynylation of N‐Sulfonyl Aldimines

The catalytic enantioselective formation of new C C bonds is an important class of organic reactions. Among them, the asymmetric additions of terminal alkynes to C=O and C=N bonds are two of the most important objectives in organic synthesis; the resulting chiral propargylic alcohols and amines are versatile building blocks for the synthesis of a wide range of natural products and pharmaceuticals. Some excellent work has been reported on the asymmetric addition of alkynes to carbonyl compounds resulting in high ee values. However, the practical enantioselective alkynylation of imines and imine derivatives to form propargylic amines is challenging because of the poor electrophilicity of the azomethine carbon. In this context, most of the studies reported so far deal with the catalytic enantioselective alkynylation of N-aryl imines by using Cu salts in combination with nitrogen-containing ligands. The leading studies of this reaction with N-aryl imines have been developed by Wei et al. , Bisai and Singh, and Benaglia and co-workers ; and Knochel and co-workers and Carreira and co-workers reported using iminium intermediates generated in situ in a three-component synthesis of propargylic amines. Other methods, which do not make use of copper complexes as the catalyst, have also been described. Hoveyda and co-workers have used peptide-based ligands in combination with Zr(OiPr)4·HOiPr to catalyze the addition of preformed mixed alkynylzinc reagents to various N-aryl aromatic imines, which gives good results with trimethylsilylethyne and lower enantioselectivities with aryl-substitued alkynes. Jiang and Si have described the addition of alkynes to a trifluoromethyl activated cyclic imine by using a stoichiometric amount of a chiral amino alcohol ligand. Recently, Bolm and co-workers have described the use of dimethylzinc to catalyze the addition of terminal alkynes toN-aryl andN-protected imines in the absence of ligands. An enantioselective version has been implemented by these authors for o-methoxyanilinederived imines by using a relatively large loading (40 mol%) of the amino alcohol ligands. In contrast, N-acyland Nsulfonyl-protected imines show enhanced reactivity because of the electron-withdrawing character of the protecting group. The alkynylation of these substrates lead to protected propargylic amines. The highly enantioselective alkynylation of N-acyl imines has been carried out by using chiral alkynylboronates and alkynylboranes, which are based on the binol and the borabicyclo[3.3.2]decane scaffolds, respectively, as reagents. However, to the best of our knowledge, the enantioselective alkynylation of N-tosyl imines has not been reported so far. Because of the increased reactivity of N-sulfonyl imines and the findings reported by Bolm and co-workers, we envisioned a dimethylzinc-mediated catalytic enantioselective alkynylation of N-sulfonyl imines by using an appropriate ligand (Scheme 1). Binol-type ligands were chosen in our study because they are known to give highly enantioselective reactions with a variety of metals, including zinc.

Enantioselective Henry addition of methyl 4-nitrobutyrate to aldehydes. Chiral building blocks for 2-pyrrolidinones and other derivatives.

A catalytic highly enantioselective Henry addition of methyl 4-nitrobutyrate to aldehydes using a Cu(II)-amino pyridine complex as catalyst is described. The products resulting from this reaction constitute a new, highly versatile family of chiral building blocks as a result of the presence of three different functional groups on the molecule. These products have been transformed into nonracemic chiral gamma-lactams, 5-hydroxy-5-substituted levulinic acid derivatives, and delta-lactones.

Alcohol Oxidation by Dioxygen and Aldehydes Catalysed by Square-Planar Cobalt(III) Complexes of Disubstituted Oxamides and Related Ligands

The square-planar cobalt(III) complexes of o-phenylenebis(N′-methyloxamidate) (Me2opba) and related oxamate (Meopba) and bis(oxamate) (opba) ligands catalyse the selective oxidation, by dioxygen and pivalaldehyde, of a wide range of secondary alcohols to the corresponding ketones, in good yields and under mild conditions in acetonitrile at room temperature. Thus, the oxidation of the series of α-alkylbenzyl alcohols PhCH(OH)R (R = Me, Et, iPr, tBu) results in the exclusive formation of ketones as a product of C−H bond cleavage, and no C−C bond cleavage products are observed in any case. The modulation of catalytic activity by ligand substituents among this series of cobalt catalysts highlights the role of oxocobalt(IV) species as the putative intermediates in these aerobic alcohol oxidation reactions. Relative reactivities for the oxidation of 1-phenylethanol increase in the order Me2opba < Meopba < opba, which correlates with the oxidising power of the postulated CoIV=O intermediate. In contrast, competitive reaction studies on the oxidation of the series of para-substituted 1-phenylethanol derivatives XPhCH(OH)CH3 (X = H, OMe, Br, CF3, NO2) show little variation in relative rate (kX/kH) with the para substituent and no correlation with Hammett σ parameters. Overall, these results are more in line with a mechanism involving concerted hydride transfer in the oxidation of alcohols by high-valent oxocobalt species (rather than a hydrogen atom transfer or an electron transfer mechanism).

Xanthones from Hypericum reflexum

Abstract The aerial parts of Hypericum reflexum contain six xanthones, two pyranoxanthones, two xanthonolignoids and a biphenyl. Six of these compounds are described for the first time.

Synthesis of Functionalized Indoles with a Trifluoromethyl‐Substituted Stereogenic Tertiary Carbon Atom Through an Enantioselective Friedel–Crafts Alkylation with β‐Trifluoromethyl‐α,β‐enones

Chiral complexes of BINOL-based ligands with zirconium tert-butoxide catalyze the Friedel-Crafts alkylation reaction of indoles with beta-trifluoromethyl-alpha,beta-unsaturated ketones to give functionalized indoles with an asymmetric tertiary carbon center attached to a trifluoromethyl group. The reaction can be applied to a large number of substituted alpha-trifluoromethyl enones and substituted indoles. The expected products were obtained with good yields and ees of up to 99%.

Sesquiterpene Lactones from Centaurea paui

Abstract A new elemanolide and two new heliangolides as well as (2R,3R)-(+)-3-hydroxy-2-methyl-butyrolactone have been isolated from Centaurea paui. The structures were elucidated by high field NMR techniques and chemical transformation.

A catalytic highly enantioselective direct synthesis of 2-bromo-2-nitroalkan-1-ols through a Henry reaction

Highly enantiomerically enriched 2-bromo-2-nitroalkan-1-ols are prepared by direct condensation of aliphatic and aromatic aldehydes with bromonitromethane in the presence of a catalytic amount of copper(ii) acetate and a C(1)-symmetric camphor-derived amino pyridine ligand.

Aerobic epoxidation of olefins catalysed by square-planar nickel(II) complexes of bis-N,N′-disubstituted oxamides and related ligands

The new square-planar nickel(II) complexes of o-phenylenebis(N′-methyloxamidate) and related ligands catalyse the aerobic epoxidation of olefins with co-oxidation of pivalaldehyde; the modulation of catalytic activity by substituents along this series of metal complexes points out the role of high-valent nicke(IV)-oxo species as the putative intermediate in these oxygen atom transfer reactions.