Catalytic Asymmetric α-Functionalization of α-Branched Aldehydes.

Aldehydes constitute a main class of organic compounds widely applied in synthesis. As such, catalyst-controlled enantioselective α-functionalization of aldehydes has attracted great interest over the years. In this context, α-branched aldehydes are especially challenging substrates because of reactivity and selectivity issues.

Synthesis of β-Hydroxy α-Amino Acids Through Brønsted Base-Catalyzed -Selective Direct Aldol Reaction of Schiff Bases of Glycine -Nitroanilide.

Here we report the highly enantio- and -selective synthesis of β-hydroxy α-amino acids from glycine imine derivatives under Brønsted base (BB) catalysis. The key of this approach is the use of benzophenone-derived imine of glycine -nitroanilide as a pronucleophile, where the -nitroanilide framework provides an efficient hydrogen-bonding platform that accounts for nucleophile reactivity and diastereoselectivity.

α-Branched Ketone Dienolates: Base-Catalysed Generation and Regio- and Enantioselective Addition Reactions.

In this study, the unique capacity of bifunctional Brønsted bases to generate α-branched ketone dienolates and control both site- and stereoselectivity of their addition reactions to representative classes of carbon electrophiles (i.e., vinyl sulfones, nitroolefins, formaldehyde) is documented.

α-Hydroxy Ketones as Masked Ester Donors in Brønsted Base Catalyzed Conjugate Additions to Nitroalkenes.

The catalyst-controlled enantioselective direct addition reaction of enolizable esters and related carboxylic acid derivatives to π electrophiles remains a difficult synthetic transformation. In this study, the suitability of α-hydroxy ketones as ester equivalents capable of being activated by bifunctional Brønsted base catalysts in the context of conjugate addition reactions to nitroolefins is demonstrated. The scope of the reaction, which affords the corresponding Michael adducts with very high stereoselectivity (diastereomeric ratio (d.

Catalytic Asymmetric Synthesis of Quaternary Barbituric Acids.

The catalytic asymmetric α-functionalization of prochiral barbituric acids, a subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5-disubstituted (quaternary) derivatives remains essentially unsolved. In this study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates that perform exceedingly in amine-squaramide catalyzed C-C bond forming reactions with vinyl ketones or Morita-Baylis-Hillmann-type allyl bromides as electrophiles. Mild acid hydrolysis of adducts affords barbituric acid derivatives with an in-ring quaternary carbon in unprecedented enantioselectivity, offering valuable materials for biological evaluations.

Controlling the α/γ-Reactivity of Vinylogous Ketone Enolates in Organocatalytic Enantioselective Michael Reactions.

The first regio-, diastereo-, and enantioselective direct Michael reaction of β,γ-unsaturated ketones with nitroolefins is enabled by Brønsted base/hydrogen-bonding bifunctional catalysis. A squaramide-substituted tertiary amine catalyzes the reaction of a broad range of β,γ-unsaturated ketones to proceed at the α-site exclusively, giving rise to adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90-98 % ee range.

β -Amino Acid N-Carboxyanhydrides Relying on Sequential Enantioselective C(4)-Functionalization of Pyrrolidin-2,3-diones and Regioselective Baeyer-Villiger Oxidation.

A catalytic enantioselective entry to β -amino acids enabling their direct coupling with nucleophiles is described. The approach is based upon an effective bifunctional Brønsted base catalyzed construction of a quaternary carbon stereocenter at C position of pyrrolidin-2,3-diones. Subsequent regioselective Baeyer-Villiger oxidation of the resultant adducts gives β -amino acid N-carboxyanhydrides as the reactive species, which can further react with nucleophiles.

Asymmetric Assembly of All-Carbon Tertiary/Quaternary Nonadjacent Stereocenters through Organocatalytic Conjugate Addition of α-Cyanoacetates to a Methacrylate Equivalent.

An efficient, highly diastereo- and enantioselective assembly of acyclic carbonyl fragments possessing nonadjacent all-carbon tertiary/quaternary stereoarrays is reported based on a Brønsted base catalyzed Michael addition/α-protonation sequence involving α-cyanoacetates and 2,4-dimethyl-4-hydroxypenten-3-one as novel methacrylate equivalent.

Development of a syn-Selective Mannich Reaction of Aldehydes with Propargylic Imines by Dual Catalysis: Asymmetric Synthesis of Functionalized Propargylic Amines.

Direct coupling of enolizable aldehydes with C-alkynyl imines is realized affording the corresponding propargylic Mannich adducts of syn configuration, thus complementing previous methods that gave access to the anti-isomers. The combination of proline and a urea Brønsted base cocatalyst is key for the reactions to proceed under very mild conditions (3-10 mol % catalyst loading, dichloromethane as solvent, -20 °C, 1.2 molar equivalents of aldehyde) and with virtually total stereocontrol (syn/anti ratio up to 99:1; ee up to 99 %).

Catalytic enantioselective quick route to aldol-tethered 1,6- and 1,7-enynes from ω-unsaturated aldehydes.

An effective asymmetric route to functionalized 1,6- and 1,7-enynes has been developed based on a direct cross-aldol reaction between ω-unsaturated aldehydes and propargylic aldehydes (α,β-ynals) promoted by combined α,α-dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio- and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,β-ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols.

Magnetic resonance evaluation of TruFit® plugs for the treatment of osteochondral lesions of the knee shows the poor characteristics of the repair tissue.

Background: Treatment of osteochondral lesions of the knee with synthetic scaffolds seems to offer a good surgical option preventing donor site morbidity. The TruFit® plug has frequently been shown to not properly incorporate into.

Objective: To evaluate the relationship between MRI findings and functional scores of patients with osteochondral lesions of the knee treated with TruFit®.

Organocatalytic C-H bond arylation of aldehydes to bis-heteroaryl ketones.

An organocatalytic aldehyde C-H bond arylation process for the synthesis of complex heteroaryl ketones has been developed. By exploiting the inherent electrophilicity of diaryliodonium salts, we have found that a commercial N-heterocyclic carbene catalyst promotes the union of heteroaryl aldehydes and these heteroaromatic electrophile equivalents in good yields. This straightforward catalytic protocol offers access to ketones bearing a diverse array of arene and heteroarene substituents that can subsequently be converted into molecules displaying structural motifs commonly found in medicinal agents.

Asymmetric catalysis of Diels-Alder reactions with in situ generated heterocyclic ortho-quinodimethanes.

The Diels-Alder reaction is probably the most powerful technology in the synthetic repertoire for single-step constructions of complex chiral molecules. The synthetic power of this fundamental pericyclic transformation has greatly increased with the emergence of asymmetric catalytic variants, and research aimed at further expanding its potential is still exciting and fascinating the chemical community. Here, we document the first asymmetric catalytic Diels-Alder reaction of in situ generated heterocyclic ortho-quinodimethanes (oQDMs), reactive diene species that have never before succumbed to a catalytic approach.

Catalytic conjugate additions of geminal bis(sulfone)s: expanding the chemistry of sulfones as simple alkyl anion equivalents.

The value of cyclic gem-bis(sulfone) 4 as a simple alkyl nucleophile equivalent in catalytic C-C bond-forming reactions is demonstrated. The 1,4-type nucleophilic additions of bis(sulfone) 4 to alpha,beta-unsaturated ketones take place by assistance of catalytic guanidine base. On the other hand, pyrrolidines are able to catalyze the conjugate addition of 4 to both enones and enals, likely by means of iminium ion activation.

Highly enantioselective conjugate additions of aldehydes to vinyl sulfones.

Joined together, organocatalysts aldehydes and sulfones: A diaryl prolinol silyl ether was found to catalyse efficiently and enantioselectively the conjugate addition of aldehydes to vinyl sulfones (see scheme). The ample synthetic utility of the resulting adducts is illustrated.

Staging, response to therapy, and restaging of lymphomas with 18F-FDG PET.

Background: We undertook this study to determine the diagnostic accuracy of (18)FDG after three cycles and at the end of chemotherapy in non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma (HL). We also evaluated the role of (67)Ga, bone marrow aspiration (BMA), and computed tomography (CT) in monitoring lymphoma treatment.

Methods: (18)FDG, (67)Ga, BMA, and CT were performed before chemotherapy on 40 untreated patients.

Trypanosoma cruzi-associated cerebrovascular disease: a case-control study in Eastern Colombia.

Trypanosoma cruzi infection is a common cause of cardiopathy in South America leading it eventually to an established stroke; however, the association between T. cruzi infection itself and cerebrovascular disease is still unknown. We did a case-control study at Eastern Colombia and found that T.