A useful protocol for achieving decarboxylative cross-coupling
(DCC) of redox-active esters (RAE, isolated or generated in situ)
and halo(hetero)arenes is reported. This pragmatically focused study
employs a unique Ag–Ni electrocatalytic platform to overcome
numerous limitations that have plagued this strategically powerful
transformation. In its optimized form, coupling partners can be combined
in a surprisingly simple way: open to the air, using technical-grade
solvents, an inexpensive ligand and Ni source, and substoichiometric
AgNO3, proceeding at room temperature with a simple commercial
potentiostat. Most importantly, all of the results are placed into
context by benchmarking with state-of-the-art methods. Applications
are presented that simplify synthesis and rapidly enable access to
challenging chemical space. Finally, adaptation to multiple scale
regimes, ranging from parallel milligram-based synthesis to decagram
recirculating flow is presented.
Quinolinium salt 3 is an effective additive that acts as a conformation control element (CCE) to promote macrocyclization to form rigid cyclophanes via olefin metathesis or Glaser-Hay coupling, which do not cyclize in the absence of the additive. The additives are easily synthesized and highly modifiable and have solubility profiles which allow for simple recovery via filtration.
A useful protocol for achieving decarboxylative cross coupling (DCC) of redox-active esters (RAE, isolated or generated in situ) and halo(hetero)arenes is reported. This pragmatically focused study employs a unique Ag-Ni electrocatalytic platform to overcome numerous limitations that have plagued this strategically powerful transformation. In its optimized form coupling partners can be combined in a surprisingly simple way: open to the air, technical grade solvents, an inexpensive ligand and Ni source, substoichiometric AgNO3, proceeding at room temperature with a simple commercial potentiostat. Most importantly all of the results are placed into context by benchmarking with state-of-the-art methods. Applications are presented that simplify synthesis and rapidly enable access to challenging chemical space. Finally, adaptation to multiple scale regimes, ranging from parallel mg-based synthesis to decagram recirculating flow is presented
The aim of this double-blind pilot trial was to compare clindamycin/primaquine with trimethoprim-sulfamethoxazole (TMP-SMZ) as primary treatment for AIDS-related Pneumocystis carinii pneumonia (PCP). The focus was on toxicity and tolerability since comparisons of efficacy were limited by the small sample size. Sixty-five individuals with a first episode of possible PCP were randomly assigned to receive clindamycin/primaquine (34 patients) or TMP-SMZ (31 patients). PCP was subsequently proven microbiologically in 27 and 22 of the patients in these respective groups. Half of the participants had an arterial partial oxygen pressure at enrollment of < or = torr. The incidence and severity of adverse reactions were lower--but not significantly lower (P = .07 and .08, respectively)--with clindamycin/primaquine. The markers of severity improved in a similar manner regardless of which regimen was administered. No significant differences were documented in outcome, duration of survival, length of the PCP-free interval, or rate of relapse. The results of this pilot study show a trend toward less toxicity with clindamycin/primaquine than with TMP-SMZ. This result must be confirmed by larger-scale clinical trials, which are also needed to better compare the efficacy of the two regimens.
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