We report a new method for the formal [3+2] reaction of aryl cyclopropyl ketones with olefins to generate highly substituted cyclopentane ring systems. The key initiation step in this process is the one-electron reduction of the ketone to the corresponding radical anion, which is accomplished using a photocatalytic system comprising Ru(bpy)32+, La(OTf)3−, and TMEDA.Cyclopentanes are important structural elements of a wide variety of organic compounds. One particularly attractive strategy for their synthesis is the [3+2] cycloaddition reaction of activated cyclopropanes with olefins.1 Several straightforward and robust methods for the synthesis of cyclopropyl ketones are available,2 and the strain associated with the threemembered ring provides a substantial driving force for the synthesis of larger carbocycles. However, most [3+2] cycloadditions of cyclopropanes reported to date have utilized "donoracceptor" cyclopropanes,3 methylene cyclopropanes,4 or similar highly activated cyclopropanes that bear substituents that predispose them towards ring-opening.5 Recently, Montgomery and Ogoshi independently reported cycloadditions of simple cyclopropyl ketones with olefins that are catalyzed by Ni 0 complexes.6 Herein, we report a mechanistically distinct method for the activation and [3+2] cycloaddition of simple aryl cyclpropyl ketones based upon our strategy for formation of anion radicals by visible light photocatalysis.7 , 8 , 9The chemistry of cyclopropyl ketyl radicals has been studied in a variety of contexts.10 Synthetically, they have most commonly been exploited for their propensity to undergo reductive fragmentations.11 , 12 To the best of our knowledge, however, they have not been examined as intermediates in [3+2] cycloaddition reactions. We recently showed that a Ru(bpy) 3 2+ photocatalyst can readily promote the one-electron reduction of a variety of aryl enones upon irradiation with visible light, and we have reported [2+2] cycloadditions involving radical anions generated in this manner.7 We wondered if similar photocatalytic conditions might be used to effect the one-electron reduction of aryl cyclopropyl ketone 1. We expected the resulting radical anion 2 to be capable of ring-opening to distonic radical anion 3. Sequential radical cyclizations might then give rise to cyclized ketyl radical 5, which, upon loss of an electron, would produce 6 as the product of formal intramolecular [3+2] cycloaddition of 1.However, under the conditions we had utilized for [2+2] cycloadditions of enones (Ru(bpy) 3 Cl 2 , LiBF 4 , i-Pr 2 NEt), we observed no evidence of ring opening of 1 ( NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript entry 1). In our original studies, we had discovered that the Lewis acidity of the lithium cation was critical to the success of the reaction and speculated that it served to activate the carbonyl compound towards one-electron reduction. We reasoned, therefore, that stronger Lewis acid additives might better activate the cyclopropyl ketone towards one...

Azides to indoles: Dirhodium(II)‐catalyzed decomposition of aryl azides was developed as a mild, functional group tolerant method for the synthesis of indoles (see scheme).

A range of 2,5-disubstituted and 2,4,5-trisubstituted pyrroles can be synthesized from dienyl azides at room temperature using catalytic amounts of ZnI2 or Rh2(O2CC3F7)4.

PurposeTo date, studies investigating the association between dairy consumption and breast cancer in women have produced conflicting results. As diet is an important, modifiable factor affecting cancer development, the aim of this study was to examine the association between dairy consumption and breast cancer risk.MethodsPubMed, Embase, and Cochrane Library databases were searched with a priority for prospective cohort studies. Case-control studies were also considered in case of the absence of a cohort study.ResultsWe analyzed 22 prospective cohort studies (1,566,940 participants) and five case-control studies (33,372 participants). High and modest dairy consumption (>600 and 400-600 g/day, respectively) significantly reduced the risk of breast cancer compared with low dairy consumption (<400 g/day; risk ratio [RR], 0.90, 95% confidence interval [CI], 0.83-0.98, and RR, 0.94, 95% CI, 0.91-0.98, respectively). A significant linear relationship between dairy consumption and breast cancer risk was found on dose-response analysis. Subgroup analysis found that yogurt (RR, 0.91; 95% CI, 0.83-0.99) and low-fat dairy (RR, 0.85; 95% CI, 0.75-0.96) reduced the risk of breast cancer, while other dairy product types did not. A reduced risk was observed for people in the United States (RR, 0.91; 95% CI, 0.83-0.99) and in those followed for ≥10 years (RR, 0.90; 95% CI, 0.81-0.99). Additionally, the highest level of dairy consumption among Asians was associated with a reduced risk of breast cancer (odds ratio, 0.74; 95% CI, 0.62-0.88).ConclusionDairy consumption was inversely associated with the risk of developing breast cancer and this effect was dependent on the dose, dairy-type, and time.

BackgroundN6-methyldeoxyadenosine (6mA or m6dA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited.ResultsWe use Tetrahymena thermophila as a model organism to examine the effects of 6mA on nucleosome positioning. Independent methods reveal the enrichment of 6mA near and after transcription start sites with a periodic pattern and anti-correlation relationship with the positions of nucleosomes. The distribution pattern can be recapitulated by in vitro nucleosome assembly on native Tetrahymena genomic DNA but not on DNA without 6mA. Model DNA containing artificially installed 6mA resists nucleosome assembling compared to unmodified DNA in vitro. Computational simulation indicates that 6mA increases dsDNA rigidity, which disfavors nucleosome wrapping. Knockout of a potential 6mA methyltransferase leads to a transcriptome-wide change of gene expression.ConclusionsThese findings uncover a mechanism by which DNA 6mA assists to shape the nucleosome positioning and potentially affects gene expression.Electronic supplementary materialThe online version of this article (10.1186/s13059-018-1573-3) contains supplementary material, which is available to authorized users.