What RFK, Jr. Got Wrong about Autism, according to Scientists Secretary of Health and Human Services Robert F. Kennedy Jr. speaks during a news conference at the Department of Health and Human Services on April 16, 2025 in Washington, DC. Most of them are genetic—the condition is between 60 and 90 percent heritable—and some involve nongenetic risk factors that might impact development during pregnancy. “We've found a great deal of the underlying [causes],” says Helen Tager-Flusberg, an autism researcher and a professor emerita at Boston University. Even so, Robert F. Kennedy, Jr., the U.S. secretary of health and human services, talks about autism in a way that suggests he thinks there are simple and direct causes. He often refers to the steady rise in autism prevalence (which is likely due to improved screening and diagnosis) as an indicator that we're in the middle of an “autism epidemic” driven by “environmental toxins.” He has also refused to disavow the long-debunked idea that vaccines cause autism. The plan involved collecting “comprehensive” private health data on autism that would represent “broad coverage” of the U.S. population, leading autism advocacy organizations, civil rights groups and research scientists to warn of medical privacy concerns. (Shortly after outlets reported on Bhattacharya's statements in April, HHS denied that it planned to create an “autism registry.”) If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. In a budget hearing on Wednesday, Kennedy called for an end to genetic research into autism. “I don't think we should be funding that genetic work anymore,” he said. The Coalition of Autism Scientists now has 258 members and is still growing. Scientific American spoke with Tager-Flusberg about Kennedy's statements this week and how the autism community is responding. In a Congressional budget hearing Wednesday afternoon, Robert F. Kennedy, Jr., said: “Autism is an epidemic, and the genes do not cause epidemics. They can contribute a vulnerability, but you need an environmental toxin. It's like cigarettes and smoking.” What was your reaction to that? There is no reason that we need to refer to the increased prevalence rates, which have been rising steadily for many years now, as an epidemic. This is not the definition of an epidemic, so I take issue with highlighting that. Second of all, genetics are the primary contributing factor to autism. We know specific genes and variants confer increased risk, even in cases where there aren't any clear environmental contributions. What we think is going on is that, as parents age, their germ cells [which develop into eggs or sperm] are changing, and so this is leading to alterations in the DNA that then confer risk for autism. Are there other nongenetic factors that might be playing a role? [Studies have shown] that [pregnant] mothers who take an antiseizure medication, particularly valproic acid, can have an increased risk of having a child with autism. But here, again, we have to think about this in a more complex way. [In such cases], the mother herself has a seizure disorder, and seizure disorders are a very common co-occurrence with autism. When RFK, Jr., said “environmental toxins” are causing autism, do you think he was talking about vaccines? Well, I listened very carefully to his testimony [on Wednesday]. And he will not rule out adverse effects of vaccines. And so, yes, I think he is probably still keeping that on his agenda. And you have the NIH director [Jay Bhattacharya] saying that we should look at everything because we want to gain the trust of people. To me, that's not the way of gaining people's trust. You don't gain trust by saying that we can just toss out all the research that we've done so far and start again. Why did you decide to form a coalition of autism scientists? It came to a head for me when I saw all the advocacy groups—self-advocates, the parent advocacy groups, nonprofit organizations—come together and issue a very strongly worded and clear statement of concern about what they were hearing from the administration. And I felt that it was really important for the voice of scientists to be heard, too. So I just contacted a small group of my colleagues and said, “I think we need to issue a press release.” I set up the Zoom call that afternoon, at five o'clock on a Friday. Clearly, there was a need for the voices of scientists to be heard. What has concerned you and your colleagues the most? They have not reached out to us at all, and I think that is very disturbing. A third thing is that the one person that was named early on [by the administration to lead research into autism] was David Geier, who is not a trained scientist. These are not databases that are suited to that kind of research because they capture only a subset of children diagnosed with autism. Many autistic people push back on this focus on finding the “roots” of autism or a “cure.” How does that pushback fit in here? People who, while needing some support, still can function and flourish individually represent one end of the spectrum. It is such a challenge for them and their families, especially some of them who engage in self-injury or very aggressive behavior. Yes, I think there is hope that we might find maybe not a complete cure but something that would significantly change their developmental course. I think we should be able to hold both ideas in our head at the same time because this is the reality of what autism is. Kennedy's approach seems to step right on that fissure in the autism community. Is there a way to prevent this rift from developing further? I have been really impressed, over the past couple of weeks, since beginning this coalition, with how [autistic] folks who are self-advocates have joined the coalition. We should not be opening up the question of vaccines again. We should be very cautious about using “registries” and make sure the research that's done is ethical and maintains the confidentiality of individuals in those databases. We also all agree that, so far, we're not hearing from the administration that they have a very deep understanding of autism. None of us have been involved in these discussions. So I think we actually have a moment in time where there is some agreement, and I think it behooves the administration to think about why that is and whether they need to change their course. Allison Parshall is an associate editor at Scientific American covering mind and brain. She writes the magazine's Contributors column and weekly online Science Quizzes. As a multimedia journalist, she contributes to Scientific American's podcast Science Quickly. Parshall's work has also appeared in Quanta Magazine and Inverse. She graduated from New York University's Arthur L. Carter Journalism Institute with a master's degree in science, health and environmental reporting. She has a bachelor's degree in psychology from Georgetown University.

We may earn commission if you buy from a link. Intended as an additional source of income for the kingdom, conditions quickly turned harsh and supplies ran short. But now, an author, museum owner, and self-described “amateur archaeologist” claims to have solved this long-standing mystery. What's more, he asserts that there was no mystery at all, the colonists were never lost, and the whole story is merely “a marketing campaign.” And he believes his latest discovery is “empirical evidence to prove it.” But he, alongside archeologist and TV presenter Mark Horton, found some small flakes of rusted metal on Hatteras Island that they believe indicates the fate of the colonists who once lived 50 miles north at Roanoke. These shavings, which the Daily Mail notes are “barely larger than a grain of rice,” are known as hammerscale, a byproduct of iron-forging. But they claim the hammerscale is more definitive proof than these previously found items, because “coins and sword hilts could have got to Hatteras through trade or a passing settler.” “The lost colony narrative was a marketing campaign,” Dawson defiantly declared. “...and now we have empirical evidence to prove it.” Dawson and Horton are not alone in the belief that the colonists went off to seek refuge with a friendly indigenous tribe. However, they are also not alone in the pantheon of those confident that their latest archaeological discovery has solved the Lost Colony mystery “once and for all.” That particularly bloody theory was “confirmed” in the 1930s, with the “discovery” of the so-called Dare Stones, a series of 48 carved stones which revealed that Virginia Dare and her father were killed by natives in 1591. But in 1941, Boyden Sparks of The Saturday Evening Post exposed these stones to be merely a hoax. When they excavated that site, some distance from Roanoke at the Bal Gra plantation along Salmon Creek, they found what they felt was fairly compelling evidence that at least some of the colonists had, in fact, left the colony and went north, to this area they dubbed Site X, as opposed to Hatteras Island. In their book, Excavating the Lost Colony Mystery, the First Colony Foundation doesn't claim to have a “smoking gun,” but instead lay out what they consider a prima facie argument in favor of their theory. So, has the Lost Colony mystery been solved? Now it's just a matter of figuring out whose solution that is. Michale Natale is a News Editor for the Hearst Enthusiast Group. As a writer and researcher, he has produced written and audio-visual content for more than fifteen years, spanning historical periods from the dawn of early man to the Golden Age of Hollywood. His stories for the Enthusiast Group have involved coordinating with organizations like the National Parks Service and the Secret Service, and travelling to notable historical sites and archaeological digs, from excavations of America' earliest colonies to the former homes of Edgar Allan Poe. AI Will Double Human Lifespan By 2030, CEO Claims ‘Dark Comets' May Have Ferried Water to Earth Humanity Is Closer Than Ever to Living Underwater A New DNA Test Could Solve the Lindbergh Baby Case

We may earn commission if you buy from a link. But however it comes about, that end might be much sooner than we thought. If you ask astrophysicist Heino Falcke, quantum physicist Michael Wondrak, and mathematician Walter van Suijlekom, they'll tell you that those last days will not erupt into a cataclysmic explosion worthy of sci-fi special effects. In 2023, the trio theorized that it was possible for other objects besides black holes to slowly evaporate away via Hawking radiation, which aroused curiosity as to how soon it could possibly happen. But don't start doomsday prepping yet—Earth still has about 5 billion years left until it gets devoured by the Sun. It might seem unfathomable, but that mind-boggling max age for the universe is far lower than the previously predicted 101100 years (which is 1 with 1100 zeroes). While this prior hypothesis did include the time it would take for black holes to evaporate, it did not factor in the evaporation of other objects. When a pair of particles forms right on the lip of a black hole's gaping maw, one can be pulled in past the inescapable event horizon, while the other escapes into nearby space. Because those particles are supposedly quantum-entangled, that rogue particle could be carrying information about the insides of a black hole (until the Hawking Information Paradox kicks in, of course). It has long been thought that only black holes emitted Hawking radiation, but in their new study, these researchers posit that a similar phenomenon could affect other ultradense objects without event horizons, such as white dwarf stars (star corpses left when the gases of a red giant dissipate) and neutron stars. Objects with strong gravitational fields evaporate faster—white dwarves, supermassive black holes, and dark matter supercluster haloes are expected to hold out for 1078 years, while neutron stars and stellar-mass black holes should hang around for about 1067 years. Anything with a gravitational field is prone to evaporating. (This includes humans, and could put a glitch in our quest for immortality. It should take 1090 years for our bodies to vanish.) Even though the intense gravitational fields of black holes should cause them to evaporate faster, they put off total annihilation as long as possible because, unlike white dwarves or neutron stars, they have no surface and tend to reabsorb some escaped particles. Both components will lead to a surface emission, which is absent in black holes.” So, in enough years to cover 78 zeroes, all that will be left of black holes—and everything else in the universe—are particles and radiation. Her work has appeared in Popular Mechanics, Ars Technica, SYFY WIRE, Space.com, Live Science, Den of Geek, Forbidden Futures and Collective Tales. She lurks right outside New York City with her parrot, Lestat. When not writing, she can be found drawing, playing the piano or shapeshifting. Experts Race to Find the Secrets of an Asteroid New Clues May Explain Why Mars Lost Its Atmosphere This Strange Stuff May Be Older Than the Cosmos

See the Dramatic Consequences of Vaccination Rates Teetering on a ‘Knife's Edge' As U.S. childhood vaccination rates sway on a “knife's edge,” new 25-year projections reveal how slight changes in national immunization could improve—or drastically reverse—the prevalence of measles, polio, rubella and diphtheria But amid a major multistate measles outbreak that has grown to hundreds of cases, a recent study published in JAMA projects that even a slight dip in current U.S. childhood vaccination rates could reverse such historic gains, which could cause some of these maladies to come roaring back within 25 years—while just a slight increase in rates could effectively squelch all four. “We were quite surprised that we're right on that knife's edge,” says the study's lead author Mathew Kiang, an assistant professor of epidemiology and population health at Stanford University. “A little bit more [vaccination coverage] and things could be totally fine; a little less and things are going to be quite bad.” If you're enjoying this article, consider supporting our award-winning journalism by subscribing. The Centers for Disease Control and Prevention and the World Health Organization formally declare a disease eliminated when there is zero continuous transmission in a specific region for 12 months or more. The U.S. achieved this milestone for measles, a viral illness that can lead to splotchy rashes, pneumonia, organ failure and other dangerous complications, in 2000. The U.S. rid itself of viral rubella, known for causing miscarriages and severe birth defects, in 2004. These are “key infectious diseases that we've eliminated from the U.S. through widespread vaccination,” says study co-author Nathan Lo, a physician-scientist at Stanford University. Kiang, Lo and their colleagues ran multiple scenarios of childhood vaccination rates over 25 years to see if the four diseases would return to endemic levels (sustained transmission in which each infected person spreads the disease to at least one other person, on average, for a 12-month period). The models estimated that a 5 percent coverage decline would lead to an estimated 5.7 million measles cases over 25 years, while a 5 percent increase would result in only 5,800 cases. Polio and rubella would require sharper vaccination rate downturns (around 30 to 40 percent) before reaching comparable risks of reemergence. While projected diphtheria cases were notably lower, Lo notes that the illness has a relatively high fatality rate and can cause rapid deterioration: “Patients with diphtheria get symptomatic and within a day or two can die.” Routine childhood immunization numbers have been slowly but steadily falling in recent years for several reasons, including missed appointments during the COVID pandemic and growing—often highly politicized—public resistance to vaccinations. Reduced U.S. vaccination rates can also cause “knock-on effects” that threaten disease eradication efforts around the world, Ferrari says. Additionally, recent funding cuts to international vaccine development programs such as USAID and Gavi, the Vaccine Alliance, will “likely lead to increases in measles, rubella, diphtheria and polio elsewhere in the world,” he says. Outbreaks of these diseases in the U.S. largely start when unvaccinated American travelers pick one up while visiting a place where it's more common. But Ferrari says the study's scenarios assumed immediate—and in some cases unrealistically high—vaccination rate drop-offs without accounting for other possible public health efforts to control disease. “Even if we anticipated an erosion of vaccination in the United States, it probably wouldn't happen instantly,” Ferrari says. Lo and Kiang argue that politically driven shifts in vaccine policy, such as reduced childhood vaccination requirements or a tougher authorization process for new vaccines, could make a 50 percent slump in vaccination rates less far-fetched. “I think that there was a lot of pushback from very smart people that 50 percent was way too pessimistic, and I think that—historically—they would have been right,” Kiang says. Kiang and Lo say that while their study shows the dangers of vast vaccine declines, it also highlights how small improvements can make a massive difference. “There's also a more empowering side, which is that the small fractions of population that push us one way can also push us the other way,” Lo says. But small percentages [of increased vaccination], we find, can really push us back into the safe territory where this alternate reality of measles reestablishing itself would not come to pass.” Young is an associate editor for health and medicine at Scientific American. Young has nearly a decade of newsroom and science journalism experience. She has appeared as a guest on radio shows, podcasts and stage events. Young has also spoken on panels for the Asian American Journalists Association, American Library Association, NOVA Science Studio and the New York Botanical Garden. Her work has appeared in Scholastic MATH, School Library Journal, IEEE Spectrum, Atlas Obscura and Smithsonian Magazine. Young studied biology at California Polytechnic State University, San Luis Obispo, before pursuing a master's at New York University's Science, Health & Environmental Reporting Program.

You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar US brain drain: the scientists seeking jobs abroad amid Trump's assault on research US brain drain: the scientists seeking jobs abroad amid Trump's assault on research Efforts launched in regions including Europe, Canada, Australia and China range from enhanced funding opportunities to new programmes dedicated to wooing scientists, many backed by tens of millions of dollars (see ‘How nations are attracting scientists'). The trend has sparked a debate about whether luring US scientists abroad is the best way to support a global research community whose leading entity is under strain — and whether other nations can compete with historically high US levels of research funding. Maria Leptin, president of the European Research Council, wants Europe to be a haven for scientists.Credit: EMBL PhotoLab Other initiatives range from government-led programmes to those launched by individual institutions seeking researchers in particular disciplines. The Spanish State Research Agency's ATRAE programme, which is designed to attract international researchers, this year has a focus on US-based scientists. “We're offering an additional funding of €200,000 for researchers who have been selected and are coming from the US,” Spanish science minister Diana Morant told Nature. The Research Council of Norway has launched a US$9.5-million scheme to recruit international researchers. The programme welcomes scientists working on climate, health, energy and artificial intelligence (AI). The Danish Chamber of Commerce has proposed a fast-track programme aimed at bringing up to 200 US researchers — in fields such as quantum technology, robotics and climate research — to Denmark over the next three years. “Austria stands as a bastion of security, favourable conditions and an unfettered research environment — qualities that are increasingly absent in the United States,” science minister Eva-Maria Holzleitner told Nature. Paris-Saclay University has deployed several initiatives to support US researchers, including PhD contracts and funded visits for scholars. It also encourages them to apply through existing programmes, including its Alembert research-chair scheme and the Chateaubriand fellowship, and it says that tenure-track positions are on offer. The Vrije Universiteit Brussel is “freeing up funds and establishing a dedicated contact point for American researchers who want to continue their work in Brussels”. The Toronto University Hospital Network has launched Canada Leads, a challenge to recruit 100 world-leading early-career scientists working across virology, regenerative medicine and areas “at risk due to shifting research funding landscapes globally”, a spokesperson says. The University of Montreal in Canada has launched a Can$25-million (US$18-million) fundraising campaign to recruit leading and early-career researchers, including those facing pressures in the United States. The programme — which has raised nearly half its funding target — will support researchers in areas such as health, AI, biodiversity and public policy. The academy is seeking investors to fund the programme, but “there has been strong interest from US-based researchers and Australians wanting to return home”, says academy president Chennupati Jagadish. In China, an advertisement began circulating on social-media platform X in February that said the technology city Shenzhen welcomes “global talents”, especially those dismissed by US institutions, Politico reported. Nature contacted several Chinese institutions to ask whether they were recruiting US scientists but did not receive a response. In France, where multiple schemes have emerged, the government has launched Choose France for Science to encourage international scientists who want to continue their work at French institutions. The Max Planck Society — Germany's prestigious network of research institutes — has started a Transatlantic Program, which aims to establish collaborative research centres with leading US institutions and will offer additional postdoc positions to US researchers. The society has committed €12 million and is working with US foundations to extend funding, a spokesperson says. But not everyone agrees that luring US talent is the right approach. Germany's Max Planck Society is among the institutions creating opportunities for US scientists to move their research abroad.Credit: Michael Bihlmayer/IMAGO via Alamy US brain drain: the scientists seeking jobs abroad amid Trump's assault on research Scientists globally are racing to save vital health databases taken down amid Trump chaos Exclusive: Trump team freezes new NSF awards — and could soon axe hundreds of grants Far-right governments seek to cut billions of euros from research in Europe US brain drain: the scientists seeking jobs abroad amid Trump's assault on research US brain drain: the scientists seeking jobs abroad amid Trump's assault on research 13 fully funded PhD positions within the MAP-ID (Multilevel Approaches to Understanding Chronic Inflammatory Diseases) US brain drain: the scientists seeking jobs abroad amid Trump's assault on research Scientists globally are racing to save vital health databases taken down amid Trump chaos Exclusive: Trump team freezes new NSF awards — and could soon axe hundreds of grants Far-right governments seek to cut billions of euros from research in Europe An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. 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Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. (2025)Cite this article As reactive intermediates and substructures of natural products and bioactive molecules, the smallest cyclic alkanes—cyclopropanes—are an attractive class of molecules for chemists. Arguably, the most general approach to their chemical synthesis involves the addition of metal carbenes to olefins. Whereas catalytic asymmetric cyclopropanations of electronically unbiased olefins with carbenoids have been reported using chiral metal complexes and engineered metalloenzymes, we now report a complementary, metal-free and highly enantioselective cyclopropanation of olefins with diazoalkanes, applying asymmetric counteranion-directed photoredox organocatalysis. We identify an ion pair featuring a thioxanthylium photoredox cation and a chiral imidodiphosphorimidate counteranion that catalyses highly enantioselective cyclopropanations of styrenes and aliphatic dienes with diazo compounds. Mechanistic investigations reveal a wavelength dependence of the enantioselectivity and suggest that the main catalytic pathway proceeds via olefin-derived radical cation intermediates. This metal-free, highly enantioselective organocatalytic approach complements previously reported methods for alkene manipulations. The synthesis of cyclopropanes1,2,3,4 via metal-catalysed carbene transfer from diazo compounds to olefins5,6,7,8 is among the best developed and most general cyclopropanations available. Enantioselective versions are documented, both with chiral metal complexes as catalysts and with engineered metalloenzymes. High effectiveness and stereocontrol have been accomplished with catalysts based on copper9, rhodium10 and ruthenium11. In particular, excellent levels of enantioselectivity have been achieved with copper(I) bisoxazoline complexes12 and with dinuclear rhodium(II) complexes, featuring chiral bidentate carboxylate, amidate or phosphate ligands13,14,15. A unique nickel carbene mediated cyclopropanation has also been reported16. Biocatalytic, new-to-nature versions of this reaction were reported by Arnold et al. in 201317, using an engineered cytochrome P450 enzyme that catalyses highly diastereo- and enantioselective cyclopropanations of styrenes with diazoesters. The Hartwig group developed iridium-modified myoglobins that catalyse the cyclopropanation of unactivated olefins18, and the Keasling group19 described a variant in which both the diazoester and the styrene were produced intracellularly. While the biocatalytic and the transition metal catalysed approaches are conceptually different, they share the initial formation of electrophilic metal carbenoids, which then engage in the actual olefin cyclopropanation (Fig. Despite these advancements, regioselectivity for substrates with multiple olefins remains a particularly challenging problem20,21,22,23. We became intrigued by the idea of designing a complementary organocatalytic approach that would not necessitate the involvement of metal carbenoids and could solve the regioselectivity problem. Organocatalytic cyclopropanations of olefins activated by an electron-withdrawing group have previously been reported24,25,26 but those of electronically unbiased olefins are unknown. Since organocatalytic activation modes for diazo alkanes or olefins, other than protonation by Brønsted acids, which appeared not to be suitable for the desired process, are not available, such a design immediately led to the challenge of how to organocatalytically activate simple olefins and/or diazo esters. We hypothesized that the abstraction of a single electron—arguably the most general strategy for activating any molecule—could be suitable here. Accordingly, we envisioned a catalytic cycle in which the olefin is activated as a radical cation upon single electron transfer to a photoexcited cationic organocatalyst associated with an enantiopure counteranion. The resulting highly reactive open-shell radical cation forms an ion pair with the enantiopure counteranion and is expected to undergo enantioselective carbon–carbon bond formation with the diazoalkane, accompanied by the loss of N2 to furnish a cyclopropane radical cation27,28,29. A final single electron transfer from the catalyst radical to this intermediate should then regenerate the cationic photocatalyst and deliver the desired cyclopropane product (Fig. This design is supported by a recently established radical cation-based photoredox catalytic cyclopropanation27 and by our own work on utilizing enantiopure counteranions in photoredox catalytic cycloadditions via olefin-derived radical cations30. The envisioned challenges associated with our concept are controlling the facial selectivity of a highly reactive open-shell radical cation intermediate and preventing the direct activation of diazoalkane to a free carbene via photolysis or energy transfer from the excited state photocatalyst, which could lead to racemic products31,32,33. a, State-of-the-art approaches to cyclopropanation of olefin with diazo compounds using metal catalysts, enzyme catalysts and the catalytic cycle. b, Our design, featuring catalytic asymmetric insertion of a diazo compound to an in situ-generated radical cation intermediate. L, ligand; M, metal. Herein, we report an organocatalytic regio- and stereoselective cyclopropanation of olefins, facilitated by asymmetric counteranion-directed photoredox catalysis (ACPC). To initiate our investigation, we studied the cyclopropanation reaction of trans-anethole (1a) and diazoester 2a in a (1:1 v/v) solvent mixture of dichloromethane (CH2Cl2) and pentane at −100 °C under irradiation by 6 W of green light. We began by exchanging the counteranion of the synthesized thioxanthylium triflate34 organophotoredox catalyst with different confined imidodiphosphorimidate (IDPi)35 anions (Fig. Encouraged by our previous studies on IDPi-catalyzed transformations, we initially selected from our assortment of privileged IDPi anions. An IDPi catalyst possessing a para-tert-butyl group as 3,3′ substituent and a trifyl core (IDPi-A) delivered the corresponding cyclopropanated product with moderate yield, good enantioselectivity (80:20 er) and poor diastereoselectivity. An analogous meta-biphenyl IDPi (IDPi-B) gave improved yield (90%) and enantioselectivity (90:10 er). Using catalyst 4C where the 3,3′ substituents of the IDPi catalyst feature a combination of meta- and para-substitution, led to a further enhancement of the enantioselectivity (95:5 er) with a dr of roughly 3:1. Having identified an optimal catalyst towards enantioselectivity, we were keen to further improve the diastereoselectivity. In this regard, meta-,para-substituted catalysts were extensively evaluated (Supplementary Table 1), and among them, spirocyclic fluorenyl substitution on the 3,3′-positions of the BINOL was found to be suitable towards this aim (4D–F). To our delight, the modified spirocyclopentyl fluorenyl substitution on the 3,3′-positions of the BINOL (IDPi-E) delivered the product not only with excellent yield and enantioselectivity but also with excellent diastereoselectivity of >20:1. Finally, fine-tuning of the inner core sulfonamide from trifluoromethyl (IDPi-E) to n-perfluoroethyl (IDPi-F) enhanced the enantiomeric ratio from 97:3 to 99:1, maintaining the excellent yield and diastereoselectivity. Remarkably, even at −100 °C, catalyst 4F rapidly furnished product 3a in a short reaction time. Lowering the catalyst loading from 2.5 to 0.5 mol% still gave full conversion with high yield even though a slight reduction of enantioselectivity (96:4 er) was observed. Optimization of the catalytic reaction for the evaluation of IDPi anions was carried out, and the yield was determined by 1H NMR using an internal standard. Next, a broad range of olefins with different double bond location and substituents at different ring positions were evaluated (Fig. 3) in the reaction with diazoester derivatives, and the cyclopropane products were obtained with good to excellent yields and enantioselectivities. Moreover, most of these products were obtained with excellent diastereoselectivities. 3-Ethyl anethole was found to be a suitable reaction partner and furnished product 3b with excellent enantioselectivity. Interestingly, 3,3-dimethyl anethole also delivered the desired product (3c) with excellent enantioselectivity, albeit with low diastereoselectivity. An olefin bearing an tert-butyldimethylsilyloxy (OTBS) substituent was also tolerated, providing product 3d with an er of 97:3 in 86% yield. Similarly, olefins featuring electron-withdrawing substituents and a heterocyclic ring furnished products 3e and 3f in excellent enantioselectivities. It is worth mentioning that other electron-rich heterocyclic olefins successfully engaged in our cyclopropanation and furnished products 3g and 3h with good to excellent level of enantioselectivity. Next, we focused on using electron neutral styrene derivatives as potential olefins for cyclopropanation. As their redox potential (>1.8 V) is higher than that of the used thioxanthylium photocatalyst (1.76 V), a photocatalyst featuring a higher redox potential was required. Gratifyingly, acridinium photocatalyst 5 (2.04 V), under red light irradiation, delivered products 3i and 3j with excellent enantioselectivity. Internal olefins gave products 3k and 3l in good yields and excellent enantioselectivity. We explored different diazoesters and found that all of the different diazoesters gave the desired products (3m and 3n) with an excellent level of enantioselectivity. Additionally, a disubstituted diazoester was found to be a suitable partner for our cyclopropanation reaction and yielded the desired product 3o in good enantioselectivity and moderate diastereoselectivity. We also investigated a diazoalkanes featuring an N-H amide-, aromatic or aliphatic keto functionality, and all furnished the desired products (3p–r) with trans-anethole in moderate to good level of enantioselectivity. Finally, even trimethylsilyl-diazomethane reacted to product 3s with promising results. Having successfully developed an organocatalytic cyclopropanation of olefins, we wondered whether our confined catalyst design may enable selectivity also with substrates bearing multiple olefins. For example, 2,5-dimethylhexa-2,4-diene (1t) is a symmetrical diene that has previously been used in the synthesis of chrysanthemic acid, a natural product also found in a variety of insecticides. In this case, the chemoselectivity issue towards obtaining the corresponding monocyclopropane has previously only been overcome by using a several fold excess of the diene23. Remarkably, using our organocatalyst system, chrysanthemic acid derivative 3t could be obtained selectively in good yield and good enantioselectivity for both diastereomers without requiring an excess of diene. Subsequently, a simple hydrolysis of ester 3t gave chrysanthemic acid (3u), preserving the enantioselectivity (Fig. We further explored the reactions of unsymmetrical conjugated dienes and trienes, delivering the desired products in good yield and enantioselectivities. It is noteworthy that an unsymmetrical conjugated diene delivered product 3v with remarkable regioselectivity (>20:1 rr) and diastereoselectivity (>20:1 dr). A diene substrate bearing an additional pendant olefin functionality (1w) was also found to be suitable for our cyclopropanation. Even the reaction with conjugated and unsymmetrical triene 1x, posing a formidable regioselectivity challenge, selectively delivered product 3x (Fig. On the other hand, we also recognized the limitations of our reaction (Supplementary Fig. Olefins bearing electron-withdrawing groups yielded the desired product in low amounts but with high enantioselectivity. Unfortunately, substrates containing amino-substituted aryl groups, indole-derived olefins, enol ethers and enamines remained unreactive under our reaction conditions. Additional diazo compounds were tested, furnishing the desired product in moderate to good yields with satisfactory enantioselectivity. However, we observed that acceptor–acceptor diazoalkanes did not undergo the transformation. Additionally, enantioenriched product 3a was derivatized to carboxylic acid product 6 without any loss of selectivities. Furthermore, a sequential reduction of the ethyl ester of 3a to the corresponding alcohol, followed by Steglich esterification gave ferrocene ester 7, the absolute configuration of which could be determined by single crystal X-ray diffraction. a, Alkene and diazoalkane variations. b, Synthesis of chrysanthemic acid. c, Scope of the dienes and trienes. d, Derivatizations dr was determined by 1HNMR. 2a for 18 h. dYield determined by 1H NMR. eUsing catalyst 5F under 6 W of red light. hUsing catalyst 5C under 6 W of blue light. TBS, tert-butyldimethylsilyl; LAH, lithium aluminium hydride; EDCI, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimid; DMAP, 4-dimethylaminopyridine. During our reaction development, lowering the catalyst loading from 2.5 to 0.5 mol% still gave full conversion with a high yield. However, a slight reduction of enantioselectivity was observed (Fig. Furthermore, the amount of diazoester was evaluated. Surprisingly, increasing the amount of the diazoester also led to a reduction of enantioselectivity (Fig. These two results hinted at a non-enantioselective, photochemical background pathway31,32,33. Since such a background reactivity may require a different wavelength, we were intrigued to explore light of different wavelengths. Indeed, a red shift was associated with a notable increase of enantioselectivity (Fig. To gain further insight into this phenomenon, we irradiated our model substrate 1a and diazoester 2a with blue or yellow light separately. Remarkably, irradiation with yellow light led to higher enantioselectivity, from 80% ee with blue light to 97% ee with yellow light. Similarly, when olefin substrates 1k and 1l were excited with yellow instead of blue light under similar conditions, an increase in enantioselectivity was observed. For example, for product 3l, the enantiomeric excess increased from 41.8% with blue light to 95.4% with yellow light (Fig. a, Reaction development under lower catalyst loading conditions. b, Reaction development on the basis of the diazo compound 2a. c, Reaction development under different light sources. d, Reactions with different olefins under blue and yellow light. To shed light on this unusual observation, we conducted absorption spectroscopy of diazoester and photocatalyst, where diazoester 2a has a maximum wavelenth of absorption (λmax) at 397 nm (Fig. 5a) and photocatalyst 4F has a λmax at 472 nm (Fig. Since the absorption band of photocatalyst 4F is very broad, the opportunity arose to excite the photocatalyst at different wavelengths and study the corresponding emission spectra. Photocatalyst 4F was excited at 472 nm (λmax) and also at a lower wavelength of 350 nm. Surprisingly, in addition to the usual emission spectra maximum at 627 nm, another maximum emission band was detected at 395 nm upon excitation at 350 nm (Fig. Interestingly the absorption band of the diazoester significantly superimposes with the emission band of the photocatalyst at lower wavelength (Fig. 5d), which led us to the hypothesis that it is this lower-wavelength excitation mode of the diazoester that is involved in the photochemical background pathway. a, The ultraviolet–visible (UV–vis) absorption spectra of 2a. b, The UV–vis absorption spectra of 4F. c, The emission spectra of 4F. e, A Stern–Volmer plot at excitation of 472 nm. f, A Stern–Volmer plot at excitation of 350 nm. Steady-state fluorescence quenching experiments with the individual reactants were conducted to obtain Stern–Volmer plots and to identify the reagent that interacts with the excited state photocatalyst. Photocatalyst 4F was first excited at 470 nm, and quenching experiments were performed separately with different amount of anethole 1a and diazoester 2a. The corresponding Stern–Volmer plots (Fig. 5e) clearly indicate that anethole 1a is responsible for the fluorescence quenching, whereas diazoester 2a has virtually no effect at this concentration. A separate set of steady-state florescence quenching experiments was conducted where the photocatalyst 4F was excited at 350 nm. In contrast, the Stern–Volmer plot (Fig. 5f) shows significant fluorescence quenching with diazoester 2a. Further standard radical probe and radical clock experiments were conducted to rule out radical process and support the radical cation mechanism, which is in line with the mechanism proposed in literature (Supplementary Fig. To gain further information regarding the stereo-specificity of our reaction, we conducted control experiment with Z-anethole (Supplementary Fig. Interestingly, under our optimized conditions, all four possible diastereoisomers were obtained in good yields. Under the optimized condition, control experiments were performed where interconversion of anethole was not observed (Supplementary Fig. These experiments further strengthen the stepwise mechanism, which is also in line with the literature. Additionally, the redox potentials of our reactants, catalyst and product were measured (Supplementary Fig. Key to the success of our organocatalytic cyclopropanation of olefins with diazoalkanes has been the use of ACPC, exploiting the positive charge of the olefin radical cation intermediate towards ion pairing with an enantiopure counteranion. Our methodology is useful for a broad range of substrates and complements previously reported metal and metalloenzyme catalyzed cyclopropanations. It also addresses the unsolved problem of regioselectivity in the reaction of substrates with different olefins. The observed wavelength-dependent enantioselectivity could serve as a valuable mechanistic probe for photoredox catalysis, potentially aiding in distinguishing between alternative reaction pathways. Observing enantioselectivity in ACPC at one wavelength confirms the involvement of radical cations in the enantiodifferentiating step, whereas its absence at this or another wavelength is consistent with alternative mechanistic pathways, such as energy transfer that proceed via neutral intermediates. Our results underscore the potential of ACPC for controlling the selectivity of radical cations in alkene manipulations, complementing previous reports. The achiral anion of the photocatalysts was exchanged with the desired enantiopure anion using the salt metathesis technique. In a gas chromatography vial, photocatalyst (25–30 mg, 1.0 equiv.) and a corresponding chiral Brønsted acid catalyst (1.05 equiv.) Then, dichloromethane (300 μl) was added, followed by saturated NaHCO3 solution (1.1 equiv., 400 μl). The reaction mixture was stirred vigorously for 30 min. Then, it was diluted with 1 ml of water and 1 ml of dichloromethane. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (5 ml x3). The organic layer was collected and dried with Na2SO4, and the solvent was removed under reduced pressure. The obtained (>95% yield) solid colourful photocatalysts were used without further purification. A gas chromatography glass vial was charged with a magnetic stirring bar and photocatalyst (0.025 equiv., 2.5 mol%). The photocatalyst was dissolved in a 1:1 (v/v) solvent mixture of CH2Cl2 and pentane (0.1 M with respect to 1a). At room temperature, anethole 1a (1 equiv.) was added followed by diazoester 2a (2 equiv.) Then, the glass vial was transferred to a −100 °C cryostat and kept at this low temperature for 30 min and then irradiated with 6 W of green light. After the desired time, the light was switched off, and after 10 min, the reaction was then quenched with saturated K2CO3 in ethanol and allowed to warm up to room temperature. The crude reaction mixture was analysed by proton nuclear magnetic resonance (1H NMR) using an internal standard and purified by SiO2 flash column chromatography using 5–10% acetone in pentane as eluent. Details on the methods, optimization studies, mechanistic studies, spectroscopic data are available in the Supplementary Information. All other data and raw and unprocessed nuclear magnetic resonance data are available from the authors upon request. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition no. Copies of the data can be obtained free of charge via CCDC at https://www.ccdc.cam.ac.uk/structures/. Lin, H.-W. & Walsh, C. T. The Chemistry of the Cyclopropyl Group (Wiley, 1987). Structure and biosynthesis of cyclopropane-containing sterols of marine origin. & Baird, M. S. Biologically active cyclopropanes and cyclopropenes. Faust, R. 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Generous support was received from the Max Planck Society, the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany's Excellence Strategy–EXC 2033–390677874–RESOLV and the European Research Council (Early stage organocatalysis) to B.L. We thank M. Meyer and H. Tüysüz for assistance with UV–vis and fluorescence spectroscopy. For help with cyclic voltammetry, we thank D. Spinnato and A. Stamoulis. The authors thank the technicians of our group and the members of our gas chromatography, mass spectrometry, HPLC, X-ray and NMR service departments. Open access funding provided by Max Planck Society. These authors contributed equally: Chendan Zhu, Sayantani Das. Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany Chendan Zhu, Sayantani Das, Avishek Guin, Chandra Kanta De & Benjamin List You can also search for this author inPubMed Google Scholar You can also search for this author inPubMed Google Scholar You can also search for this author inPubMed Google Scholar You can also search for this author inPubMed Google Scholar You can also search for this author inPubMed Google Scholar carried out the methodology. carried out the investigations. carried out writing of the original draft. carried out review and editing. Correspondence to Chandra Kanta De or Benjamin List. is listed as an inventor on patent no. WO 2017/037141 filed by the Max-Planck-Institut für Kohlenforschung covering the IDPi catalyst class and its applications in asymmetric synthesis. are listed as inventors on a patent on an improved synthesis of imidodiphosphoryl-derived catalysts using hexachlorophosphazonium salts (patent no. EP 3 981 775 A1) filed by the Max-Planck-Institut für Kohlenforschung. and A.G. declare no competing interests. Nature Catalysis thanks the anonymous reviewers for their contribution to the peer review of this work. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Methods, Figs. CIF file of the crystal structure of compound 7. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. 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