A novel method for the low-temperature generation of Co2(CO)6-complexed propargyl radicals is developed. It consists of an in situ preparation of the respective cationic species (−50 to −10 °C) and their rapid reduction with cobaltocene, Cp2Co, at −50 °C. The optimized experimental protocol is applied to both inter- and intramolecular reactions, affording topologically diverse α-aryl and α-napthyl, d,l- and meso-1,5-hexadiynes and 1,5-cyclodecadiynes. The d,l configuration is the most preferable steric arrangement in intermolecular radical C–C bond-forming reactions (d,l 69–92%), while a reversal of stereoselectivity is observed in intramolecular cyclizations (meso 79%). Under oxidizing conditions (Ce4+), decomplexation affords d,l-3,4-diaryl- and d,l-3,4-(1-/2-naphthyl)-1,5-hexadiynes in good to excellent yields (47–98%). An enhanced functional tolerance is showcased by introducing peripheral acid-sensitive functionalities, such as benzyloxy and methylenedioxy groups, and carrying out a five-step conversion schemefrom commercial aromatic aldehydes to radical dimersunder nonacidic conditions.

Radical coupling reactions of Co 2 (CO) 6 -complexed 1,4-enynes occur in a regio-and stereoselective fashion, providing access to 3E,7E-decadiene-1,9-diynes in excellent yields (84−99%). The formation of contiguous quaternary carbon atoms follows a tandem allylic rearrangement that projects an original reaction site gamma to the metal core. Propargyl alcohols with an α-alkenyl group as a substituent are treated with HBF 4 , followed by the reduction of the highly conjugated propargyl cations with zinc. The scope of the reaction is expanded to include 1,4-enyne complexes with cyclic and acyclic substituents gamma to the metal core, as well as aliphatic and aromatic substituents attached to the acetylenic termini. The alternative design includes relocation of the cation generation siteα-to-γprior to the reduction step, employing either the cation isolation technique with HBF 4 or an in situ generation of ionic propargyl triflates with Tf 2 O. Retention of the reaction site in 1,3-enynes is observed in both γ-alcohols and γ-Me ethers, affording respective γ,γ-radical dimers in excellent yields (98− 99%). ■ INTRODUCTIONAssembling of organic molecules with contiguous quaternary carbon atoms has long represented a formidable synthetic challenge. 1,2 Besides a purely academic interest of developing access to topologically complex molecular assemblies, significance of this research area was determined by the presence of said molecular units in natural steroids and their construction via biomimetic polyene cyclization reactions. Select natural compounds with vicinal quaternary carbons were reported in folk medicine to treat certain diseases, thus providing a new impetus to the synthetic studies that could potentially mimic, or even outperform, "natural" pathways and provide access to lead compounds for drug development. Among the alternative approaches for assembling adjacent quaternary carbon atoms are intramolecular Heck cyclizations, 2a−c biomimetic cascade polyene cyclizations, 2d,e trans-annular Diels−Alder reactions, 2f Ireland−Claisen 2g and thio-Claisen 2h rearrangements, and intermolecular Michael addition reactions. 2i While providing access to topologically diverse molecular targets, most of the existing methods are characterized by an excessive number of steps, low overall yields, structural and functional limitations, and a relatively narrow category of organic molecules that can be assembled with a given methodology. Radical reactions were used in the photochemical decarbonylation of heavily substituted ketones with the methodology being constrained to a set of substrates with functional groups that could lower the C−C bond dissociation energies. 3a−c Diastereoselectivity of the radical bond formation varied in the liquid phase (dr 1.1− 2.1) 3a with the major, d,l-diastereomer being exclusively formed in solid-phase reactions of acyclic 3a and cyclic 3b ketones. Although being used in the total synthesis of the sesquiterpene herbertenolide, 3c radical reactions remain underrepresented in targeted synthesis...

BACKGROUND: Over 90% of all cases of malaria worldwide occur in Africa. Current methods of diagnosis are time and labor intensive, and could lead to delayed treatment. METHODS:In this study we investigated the effectiveness of measurements of spleen, liver, and optic nerve sheath diameter (ONSD) in identifying patients with malaria or severe malaria through the use of hand-held ultrasound devices. We recruited 40 adult patients with malaria and 16 adult control subjects at two hospitals in Mwanza, Tanzania. Ultrasonographic diagnosis was compared with rapid antigen diagnostic test and peripheral blood smear as the gold standards. An receiver operating characteristic curve test was performed to determine the most optimal diagnostic threshold for malaria and severe malaria, using each of the measurements for liver size, spleen size, and ONSD. The thresholds were determined to be >12 cm for spleen length and >15.1 cm for liver length, whereas ONSD was not signifi cant in this study. RESULTS:The sensitivities for malaria diagnosis were 66.7% and 58.3% for liver and spleen length respectively, suggesting that these measurements may not be suitable for identifying patients with severe malaria. However, the high specificity of 90.9% for spleen length and the acceptable specifi city of 75.0% for liver length suggest that these measurements can be used as a method to eliminate false-positive diagnoses (i.e. patients who do not have severe malaria but are classifi ed as having it by a test with a high sensitivity), giving a high positive predictive value. CONCLUSIONS:We report a high specifi city for spleen size and a moderate specifi city for liver size in the ultrasonographic diagnosis of severe malaria. Thus when paired with a highly sensitive method of malaria diagnosis, ultrasonographic measurement of spleen and liver size is promising as part of a diagnostic algorithm for malaria. It could be used to stratify risk in patients diagnosed with malaria and assist in their triage. If no sensitive tests are available, ultrasound might be useful to suggest malaria as a cause of a patient's constellation of clinical symptoms.