Metal-Free Diastereo- and Enantioselective Dearomative Formal [3 + 2] Cycloaddition of 2-Nitrobenzofurans and Isocyanoacetate Esters

The diastereo- and enantioselective dearomative formal [3 + 2] cycloaddition of 2-nitrobenzofurans and α-aryl-α-isocyanoacetate esters provides tricyclic compounds bearing the 3a,8b-dihydro-1H-benzofuro[2,3-c]pyrrole framework with three consecutive stereogenic centers. The reaction was enabled by a cupreine-ether organocatalyst. The reaction products were obtained with almost full diastereoselectivity and with excellent enantiomeric excesses for a number of substituted 2-nitrobenzofurans and isocyanoacetates

Organocatalytic enantioselective 1,6-aza-Michael addition of isoxazolin-5-ones to p-quinone methides

A thiourea-Brønsted base bifunctional catalyst allowed the enantioselective 1,6-aza-Michael addition of isoxazolin-5-ones to p-quinone methides to give isoxazolin-5-ones having a chiral diarylmethyl moiety attached to the N atom with fair to good yields and enantiomeric excesses. To the best of our knowledge this reaction represents the first example of enantioselective N-alkylation of isoxazolin-5-ones as well as the first example of enantioselective 1,6-aza-Michael reaction involving p-quinone methides

Enantioselective Synthesis of 5‑Trifluoromethyl-2-oxazolines under Dual Silver/Organocatalysis

The first enantioselective formal [3 + 2] cycloaddition between α-isocyanoesters and trifluoromethylketones to give 5-trifluoromethyl-2-oxazolines bearing two contiguous stereogenic centers, one of them being a quaternary stereocenter substituted with a CF3 group, has been developed. The reaction is based upon a multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as Lewis acid. The reaction could be achieved with a range of aryl and heteroaryl trifluoromethyl ketones, and the resulting oxazolines were obtained with good to excellent diastereo- and enantioselectivity

Enantioselective synthesis of chiral oxazolines from unactivated ketones and isocyanoacetate esters by synergistic silver/organocatalysis

A multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag+ as Lewis acid has been applied in the reaction of unactivated ketones with tert-butyl isocyanoacetate to give chiral oxazolines bearing a quaternary stereocenter. The formal [3+2] cycloaddition provided high yields of the corresponding cis-oxazolines with good diastereoselectivity and excellent enantioselectivity, being applied to aryl-alkyl and alkyl-alkyl ketones

Enantioselective zinc-mediated conjugate alkynylation of saccharin-derived 1-aza-butadienes

The enantioselective 1,4-alkynylation of conjugated imines derived from saccharin with aryl- and alkyl-substituted terminal alkynes has been achieved. The reaction mediated by diethylzinc in the presence of a catalytic amount of a bis(hydroxy)malonamide chiral ligand provides the corresponding imines bearing a propargylic stereocenter with moderate yields and fair to excellent enantioselectivities

A Cu-BOX catalysed enantioselective Mukaiyama-aldol reaction with difluorinated silyl enol ethers and acylpyridine N-oxides

A Cu(II)/BOX complex catalyses the enantioselective addition of difluorinated silyl enol ethers to acylpyridine N-oxides. The reaction provides difluorinated chiral tertiary alcohols of great interest in medicinal chemistry. These compounds are obtained in moderate to excellent yields and with high enantioselectivities. The stereochemical outcome of the reaction has been explained by DFT calculations

Risk factors for non-melanoma skin cancer in kidney transplant patients in a Spanish population in the Mediterranean region

Non-melanoma skin cancer (NMSC) is the most frequent malignancy in organ transplant recipients. The aetiology of NMSC after transplant is multifactorial. The aim of this study was to determine the clinical and environmental factors involved in the development of NMSC in a Spanish kidney transplant population from the Mediterranean region. A total of 289 patients who had received a kidney transplant during the period January 1996 to December 2010 were included in the study. Both prospective and retrospective data were used. All patients underwent a structured interview and a complete examination of the skin. After a median follow-up of 72 months (range 12-180 months), 73 of the 289 patients (25.2%) developed 162 tumours. The ratio of basal cell carcinoma to squamous cell carcinoma was 2.21:1. The cumulative incidence of NMSC increased with the duration of immunosuppression, from 20.78% at 5 years, to 37.35% at 10 years to 53.08% at 15 years after transplantation. Age at the time of transplant, phototype and occupational sun exposure were associated with a higher risk of NMSC. NMSC is a significant clinical problem in kidney transplant recipients. This has implications for the development of prevention and surveillance strategies. Clinical and environmental factors may be used to identify those patients who are at risk for NMSC

Enantioselective addition of sodium bisulfite to nitroalkenes. A convenient approach to chiral sulfonic acids

An enantioselective organocatalytic addition of sodium bisulfite to (E)-nitroalkenes has been developed by using a chiral bifunctional organocatalyst. The present methodology provides a variety of chiral β-nitroethanesulfonic acid compounds (17 examples) with excellent results: up to 99% yield and excellent enantioselectivity (up to 96% ee). The reaction tolerates (hetero)aryl and alkyl substituents on the β-nitroalkenes, and β,β-disubstituted nitroalkenes