Cyclopropanone derivatives have long been considered unsustainable synthetic intermediates because of their extreme strain and kinetic instability.R eported here is the enantioselective synthesis of 1-sulfonylcyclopropanols,a ss table yet powerful equivalents of the corresponding cyclopropanone derivatives,bya-hydroxylation of sulfonylcyclopropanes using ab is(silyl) peroxide as the electrophilic oxygen source. This work constitutes the first general approach to enantioenriched cyclopropanone derivatives.B oth the electronic and steric nature of the sulfonyl moiety,w hich serves as ab aselabile protecting group and confers crystallinity to these cyclopropanone precursors,w ere found to have ac rucial impact on the rate of equilibration to the corresponding cyclopropanone.T he utility of these cyclopropanone surrogates is demonstrated in amild and stereospecific formal [3+ +1] cycloaddition with simple hydroxylamines,l eading to the efficient formation of chiral b-lactam derivatives.

Background As an alternative to vitamin K antagonist and low-dose aspirin (< 325 mg), non-vitamin K oral anticoagulants are available for the prevention of stroke in patients with atrial fibrillation. However, the mortality risk associated with these drugs in daily practice remains unclear. Objective To evaluate the risk of all-cause mortality associated with non-Vitamin K antagonist oral anticoagulants, vitamin K antagonists or aspirin in patients with atrial fibrillation. Setting A cohort study conducted among atrial fibrillation patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). Method New users of vitamin K antagonists, non vitamin K oral anticoagulants, low-dose aspirin, or combination therapy were followed from the date of first prescription to the date of death, as recorded in the UK datalink. Cox proportional hazard models estimated the hazard ratio (HR) of all-cause mortality for users of NOACs, aspirin, or combination use, as compared to vitamin K antagonist. Analyses were adjusted for confounders. Main outcome measure All-cause mortality. Results We identified 31,497 patients. Non vitamin K antocoagulant use (adjusted HR [aHR] = 1.42; 95% Confidence Interval [CI] 1.18-1.71) and aspirin use (aHR = 1.64; 95% CI 1.57-1.77) were both significantly associated with a higher mortality risk than use of vitamin K antagonists. The higher mortality risk for the non vitamin K anticoagulant use was observed in men (aHR = 1.72; 95% CI 1.25-2.36), but not in women (aHR = 1.28; 95% CI 0.92-1.79. Compared to vitamin K antagonists, mortality risk associated with the non vitamin K anticoagulants and aspirin use was significantly increased in patients with higher stroke risk (CHA 2 DS 2-VASc > 2). Conclusion Non vitamin K oral anticoagulants are associated with a higher risk on all-cause mortality, particularly in men and in patients with higher stroke risk.

Cyclopropanone derivatives have long been considered unsustainable synthetic intermediates because of their extreme strain and kinetic instability.R eported here is the enantioselective synthesis of 1-sulfonylcyclopropanols,a ss table yet powerful equivalents of the corresponding cyclopropanone derivatives,bya-hydroxylation of sulfonylcyclopropanes using ab is(silyl) peroxide as the electrophilic oxygen source. This work constitutes the first general approach to enantioenriched cyclopropanone derivatives.B oth the electronic and steric nature of the sulfonyl moiety,w hich serves as ab aselabile protecting group and confers crystallinity to these cyclopropanone precursors,w ere found to have ac rucial impact on the rate of equilibration to the corresponding cyclopropanone.T he utility of these cyclopropanone surrogates is demonstrated in amild and stereospecific formal [3+ +1] cycloaddition with simple hydroxylamines,l eading to the efficient formation of chiral b-lactam derivatives.

Cyclopropanone derivatives have long been considered unsustainable synthetic intermediates due to their extreme strain and kinetic instability. Herein, we report the enantioselective synthesis of 1-sulfonylcyclopropanols as stable yet powerful equivalents of the corresponding cyclopropanone derivatives, via α-hydroxylation of sulfonylcyclopropanes using a bis(silyl) peroxide as electrophilic oxygen source. Both the electronic and steric nature of the sulfonyl moiety, which serves as a base-labile protecting group and confers crystallinity to these cyclopropanone precursors, were found to have a crucial impact on the rate of equilibration to the corresponding cyclopropanone, highlighting the modular nature of these precursors and the potential for their widespread adoption as synthetic intermediates. The utility of these cyclopropanone surrogates is demonstrated in a mild and stereospecific formal [3+1] cycloaddition with simple hydroxylamines acting here as nitrene equivalents, leading to the efficient formation of chiral β-lactam derivatives.