{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:17:10Z","timestamp":1792894630537,"version":"4.5.0"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"30","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000183","name":"Army Research Office","doi-asserted-by":"publisher","award":["W911NF-22-2-0170"],"award-info":[{"award-number":["W911NF-22-2-0170"]}],"id":[{"id":"10.13039\/100000183","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM124791"],"award-info":[{"award-number":["R35 GM124791"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stereochemically complex, sp3-rich rings have attracted significant interest in drug discovery because of their ability to mitigate the physicochemical liabilities associated with flat aromatic rings. Cyclopropanes are attractive targets in this regard because they have unique three-dimensional structures and are resistant to metabolism. Numerous catalytic enantioselective alkene cyclopropanation reactions have been developed using carbene precursors. However, most of these methods use energetic reagents and are restricted to specific classes of resonance-stabilized carbenes. Here, we report a catalytic asymmetric cyclopropanation reaction using chloroform as a methylidyne equivalent and Zn as a stoichiometric reductant. The products are metallocyclopropanes that can be further functionalized in a telescoped process to yield halo-, aryl-, allyl-, alkynyl-, vinyl-, and other substituted cyclopropanes in highly enantioenriched form. A notable feature of the reaction is the high degree of cis diastereoselectivity, which is controlled by the large N-aryl substituent of the ligand. Application in the parallel synthesis of enantioenriched 1,2-diarylcyclopropanes bearing pharmaceutically relevant heterocycles is demonstrated.<\/jats:p>","DOI":"10.1021\/jacs.6c05240","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:11:00Z","timestamp":1785129060000},"page":"31931-31939","source":"Crossref","is-referenced-by-count":2,"title":["Catalytic Asymmetric\nMetallocyclopropanation Reactions\nUsing Chloroform as a Carbyne Equivalent"],"prefix":"10.1021","volume":"148","author":[{"given":"Raymond J.","family":"Martinez","sequence":"first","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Garg","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke R.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9621-1974","authenticated-orcid":true,"given":"Alexander J.","family":"Rago","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. , , , ,","place":["North Chicago, Illinois, United States, 60064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon M.","family":"Young","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. , , , ,","place":["North Chicago, Illinois, United States, 60064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Garcia","family":"Chavez","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. , , , ,","place":["North Chicago, Illinois, United States, 60064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-5356","authenticated-orcid":true,"given":"Eric A.","family":"Voight","sequence":"additional","affiliation":[{"name":"AbbVie, Inc. , , , ,","place":["North Chicago, Illinois, United States, 60064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-915X","authenticated-orcid":true,"given":"Christopher","family":"Uyeda","sequence":"additional","affiliation":[{"name":"Purdue University , , , ,","place":["West Lafayette, Indiana, United States, 47907"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"issue":"6631","key":"2026080511143277500_cit1a","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1126\/science.ade5110","article-title":"Single\u2013carbon atom transfer\nto \u03b1,\u03b2-unsaturated amides from N-heterocyclic carbenes","volume":"379","author":"Kamitani","year":"2023","journal-title":"Science"},{"issue":"6706","key":"2026080511143277500_cit1b","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1126\/science.ado4564","article-title":"Ph3PCN2: A stable reagent for carbon-atom transfer","volume":"385","author":"Koike","year":"2024","journal-title":"Science"},{"issue":"43","key":"2026080511143277500_cit2a","doi-asserted-by":"publisher","first-page":"5239","DOI":"10.1016\/S0040-4039(01)89263-7","article-title":"Asymmetric\ninduction in carbenoid reaction by means of a dissymmetric copper\nchelate","volume":"7","author":"Nozaki","year":"1966","journal-title":"Tetrahedron Lett."},{"issue":"10","key":"2026080511143277500_cit2b","doi-asserted-by":"publisher","first-page":"3300","DOI":"10.1021\/ja00791a038","article-title":"Copper(I) catalysis in cyclopropanations\nwith diazo compounds. Role of olefin coordination","volume":"95","author":"Salomon","year":"1973","journal-title":"J. Am. Chem. Soc."},{"issue":"5","key":"2026080511143277500_cit3a","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1021\/cr00075a013","article-title":"Catalytic methods for metal carbene\ntransformations","volume":"86","author":"Doyle","year":"1986","journal-title":"Chem. Rev."},{"issue":"7177","key":"2026080511143277500_cit3b","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature06485","article-title":"Catalytic C-H functionalization by\nmetal carbenoid\nand nitrenoid insertion","volume":"451","author":"Davies","year":"2008","journal-title":"Nature"},{"issue":"6156","key":"2026080511143277500_cit3c","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1126\/science.1243200","article-title":"Direct\nSpectroscopic Characterization of a Transitory Dirhodium Donor-Acceptor\nCarbene Complex","volume":"342","author":"Kornecki","year":"2013","journal-title":"Science"},{"issue":"23","key":"2026080511143277500_cit3d","doi-asserted-by":"publisher","first-page":"13810","DOI":"10.1021\/acs.chemrev.7b00382","article-title":"Transition-Metal-Catalyzed\nCross-Couplings through Carbene Migratory Insertion","volume":"117","author":"Xia","year":"2017","journal-title":"Chem. Rev."},{"issue":"7690","key":"2026080511143277500_cit4a","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/nature25185","article-title":"Generating\ncarbyne equivalents with photoredox catalysis","volume":"554","author":"Wang","year":"2018","journal-title":"Nature"},{"issue":"13","key":"2026080511143277500_cit4b","doi-asserted-by":"publisher","first-page":"6943","DOI":"10.1002\/anie.202014775","article-title":"\u03b1-Diazo Sulfonium Triflates:\nSynthesis, Structure, and Application to the Synthesis of 1-(Dialkylamino)-1,2,3-triazoles","volume":"60","author":"Li","year":"2021","journal-title":"Angew. Chem., Int. Ed."},{"issue":"30","key":"2026080511143277500_cit4c","doi-asserted-by":"publisher","first-page":"11337","DOI":"10.1021\/jacs.1c06287","article-title":"Carbon Atom Insertion into Pyrroles and Indoles Promoted\nby Chlorodiazirines","volume":"143","author":"Dherange","year":"2021","journal-title":"J. Am. Chem. Soc."},{"issue":"49","key":"2026080511143277500_cit4d","doi-asserted-by":"publisher","first-page":"26540","DOI":"10.1021\/jacs.3c10751","article-title":"General Synthesis of N-Alkylindoles\nfrom N,N-Dialkylanilines via [4 + 1] Annulative Double C\u2013H\nFunctionalization","volume":"145","author":"Zhang","year":"2023","journal-title":"J. Am. Chem. Soc."},{"issue":"3","key":"2026080511143277500_cit4e","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/s41929-023-01089-x","article-title":"Ring expansion of indene\nby photoredox-enabled functionalized carbon-atom insertion","volume":"7","author":"Wu","year":"2024","journal-title":"Nat. Catal."},{"issue":"31","key":"2026080511143277500_cit4f","doi-asserted-by":"publisher","first-page":"21837","DOI":"10.1021\/jacs.4c06158","article-title":"Rh-Catalyzed\nEnantioselective Single-Carbon Insertion of Alkenes","volume":"146","author":"Teo","year":"2024","journal-title":"J. Am. Chem. Soc."},{"issue":"16","key":"2026080511143277500_cit4g","doi-asserted-by":"publisher","first-page":"13120","DOI":"10.1021\/jacs.5c02331","article-title":"Rh-Catalyzed Enantioselective Aryl C\u2013H Bond\nCyclopropylation","volume":"147","author":"Palomo","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026080511143277500_cit16h","doi-asserted-by":"publisher","first-page":"3852","DOI":"10.1021\/jacs.5c21901","article-title":"A Diazo-free Equivalent of the Unsubstituted\nCarbyne Cation: Straightforward Synthesis of Naphthalenes and Pyridines\nvia [12\/13CH]+ Insertion","volume":"148","author":"Wenzel","year":"2026","journal-title":"J. Am. Chem. Soc."},{"issue":"19","key":"2026080511143277500_cit5a","doi-asserted-by":"publisher","first-page":"5323","DOI":"10.1021\/ja01552a080","article-title":"A New Synthesis\nof Cyclopropanes\nfrom Olefins","volume":"80","author":"Simmons","year":"1958","journal-title":"J. Am. Chem. Soc."},{"key":"2026080511143277500_cit5b","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/0471264180.or058.01","article-title":"Simmons-Smith\nCyclopropanation Reaction","volume":"58","author":"Charette","year":"2001","journal-title":"Org. React."},{"issue":"9","key":"2026080511143277500_cit6","doi-asserted-by":"publisher","first-page":"7282","DOI":"10.1021\/jacs.4c13269","article-title":"Asymmetric Radical\nCyclopropanation of \u03b1,\u03b2-Unsaturated Amides with \u03b1-Boryl\nand \u03b1-Silyl Dibromomethanes via Cr(II)-Based Metalloradical\nCatalysis","volume":"147","author":"Wang","year":"2025","journal-title":"J. Am. Chem. Soc."},{"issue":"6756","key":"2026080511143277500_cit7a","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1126\/science.adw4177","article-title":"Harnessing\ncarbene polarity: Unified catalytic access to donor, neutral, and\nacceptor carbenes","volume":"389","author":"Nguyen","year":"2025","journal-title":"Science"},{"key":"2026080511143277500_cit21b","doi-asserted-by":"publisher","first-page":"102968","DOI":"10.1016\/j.chempr.2026.102968","article-title":"Skeletal editing by iron-catalyzed carbene insertion\nof trichloromethanes","author":"DeMuynck","year":"2026","journal-title":"Chem"},{"issue":"17","key":"2026080511143277500_cit8","doi-asserted-by":"publisher","first-page":"9441","DOI":"10.1021\/jacs.3c01949","article-title":"Catalytic Asymmetric\nCyclopropanations with Nonstabilized Carbenes","volume":"145","author":"Berger","year":"2023","journal-title":"J. Am. Chem. Soc."},{"issue":"42","key":"2026080511143277500_cit9","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202308913","article-title":"Nucleophilic\nCarbenes Derived from Dichloromethane","volume":"62","author":"Liu","year":"2023","journal-title":"Angew.\nChem., Int. Ed."},{"issue":"3","key":"2026080511143277500_cit10a","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1021\/ja017230d","article-title":"First Evidence\nfor the Formation of a Geminal Dizinc Carbenoid: A Highly Stereoselective\nSynthesis of 1,2,3-Substituted Cyclopropanes","volume":"124","author":"Charette","year":"2002","journal-title":"J. Am. Chem. Soc."},{"issue":"38","key":"2026080511143277500_cit10b","doi-asserted-by":"publisher","first-page":"13140","DOI":"10.1021\/ja054328+","article-title":"Diastereoselective Zinco-Cyclopropanation\nof Chiral Allylic Alcohols with gem-Dizinc Carbenoids","volume":"127","author":"Fournier","year":"2005","journal-title":"J. Am. Chem. Soc."},{"issue":"43","key":"2026080511143277500_cit10c","doi-asserted-by":"publisher","first-page":"15624","DOI":"10.1021\/ja906033g","article-title":"Enantioselective Synthesis of 1,2,3-Trisubstituted\nCyclopropanes Using gem-Dizinc Reagents","volume":"131","author":"Zimmer","year":"2009","journal-title":"J.\nAm. Chem. Soc."},{"issue":"3","key":"2026080511143277500_cit11a","doi-asserted-by":"publisher","first-page":"0025","DOI":"10.1038\/s41570-017-0025","article-title":"Well-defined\nnickel and palladium precatalysts for cross-coupling","volume":"1","author":"Hazari","year":"2017","journal-title":"Nat. Rev. Chem."},{"issue":"7","key":"2026080511143277500_cit11b","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202211167","article-title":"Rapid and Modular Access to Vinyl Cyclopropanes Enabled\nby Air-stable Palladium(I) Dimer Catalysis","volume":"62","author":"Mendel","year":"2023","journal-title":"Angew. Chem., Int. Ed."},{"issue":"50","key":"2026080511143277500_cit12","doi-asserted-by":"publisher","first-page":"26332","DOI":"10.1002\/anie.202109482","article-title":"Three-Component\nDifunctionalization\nof Cyclohexenyl Triflates: Direct Access to Versatile Cyclohexenes\nvia Cyclohexynes","volume":"60","author":"Cho","year":"2021","journal-title":"Angew. Chem., Int. Ed."},{"issue":"8019","key":"2026080511143277500_cit13","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/s41586-024-07555-1","article-title":"Dynamic stereomutation of vinylcyclopropanes\nwith metalloradicals","volume":"631","author":"Mendel","year":"2024","journal-title":"Nature"},{"issue":"19","key":"2026080511143277500_cit14","doi-asserted-by":"publisher","first-page":"8712","DOI":"10.1021\/acs.jmedchem.6b00472","article-title":"The \u201cCyclopropyl\nFragment\u201d is a Versatile Player that Frequently Appears in\nPreclinical\/Clinical Drug Molecules","volume":"59","author":"Talele","year":"2016","journal-title":"J. Med.\nChem."},{"issue":"52","key":"2026080511143277500_cit15a","doi-asserted-by":"publisher","first-page":"16110","DOI":"10.1002\/anie.201608680","article-title":"Gram-Scale Synthesis of Chiral Cyclopropane-Containing\nDrugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring\nComplementary Stereoselectivity","volume":"55","author":"Bajaj","year":"2016","journal-title":"Angew. Chem.,\nInt. Ed."},{"issue":"5","key":"2026080511143277500_cit15b","doi-asserted-by":"publisher","first-page":"4188","DOI":"10.1021\/jacs.4c13832","article-title":"Automated Flow Synthesis of Artificial Heme Enzymes\nfor Enantiodivergent Biocatalysis","volume":"147","author":"Fittolani","year":"2025","journal-title":"J. Am. Chem.\nSoc."},{"issue":"27","key":"2026080511143277500_cit16","doi-asserted-by":"publisher","first-page":"11884","DOI":"10.1021\/jacs.0c04462","article-title":"Stereoselective Functionalization\nof Racemic Cyclopropylzinc Reagents via Enantiodivergent Relay Coupling","volume":"142","author":"An","year":"2020","journal-title":"J. Am. Chem. Soc."},{"issue":"14","key":"2026080511143277500_cit17","doi-asserted-by":"publisher","first-page":"11622","DOI":"10.1021\/acs.jmedchem.4c01122","article-title":"An Update\non the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved\nPharmaceuticals (2013\u20132023)","volume":"67","author":"Marshall","year":"2024","journal-title":"J. Med.\nChem."},{"issue":"21","key":"2026080511143277500_cit18a","doi-asserted-by":"publisher","first-page":"6752","DOI":"10.1021\/jm901241e","article-title":"Escape from\nFlatland: Increasing Saturation as an Approach to Improving Clinical\nSuccess","volume":"52","author":"Lovering","year":"2009","journal-title":"J. Med. Chem."},{"issue":"4","key":"2026080511143277500_cit18b","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1039\/D0MD00370K","article-title":"Put a ring\non it: application of small aliphatic rings in medicinal chemistry","volume":"12","author":"Bauer","year":"2021","journal-title":"RSC Med. Chem."},{"issue":"10","key":"2026080511143277500_cit19","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1021\/acs.orglett.7b00707","article-title":"Synthesis of Substituted Cyclopropanecarboxylates\nvia Room Temperature Palladium-Catalyzed \u03b1-Arylation of Reformatsky\nReagents","volume":"19","author":"Greszler","year":"2017","journal-title":"Org. Lett."},{"key":"2026080511143277500_cit22","doi-asserted-by":"publisher","first-page":"134830","DOI":"10.1016\/j.tet.2025.134830","article-title":"A catalytically generated\ntransition\nmetal analog of the Simmons\u2013Smith reagent","volume":"185","author":"Werth","year":"2025","journal-title":"Tetrahedron"},{"issue":"21","key":"2026080511143277500_cit23","doi-asserted-by":"publisher","first-page":"3504","DOI":"10.1039\/b711573c","article-title":"Gold nanoparticle-initiated\nfree radical oxidations and halogen abstractions","volume":"5","author":"Ionita","year":"2007","journal-title":"Org. Biomol. Chem."}],"container-title":["Journal of the American\nChemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.6c05240","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/30\/31931\/66254343\/jacs.6c05240.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/30\/31931\/66254343\/jacs.6c05240.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:26:20Z","timestamp":1785943580000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/148\/30\/31931\/5232282\/Catalytic-Asymmetric-Metallocyclopropanation"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":40,"journal-issue":{"issue":"30","published-online":{"date-parts":[[2026,7,25]]},"published-print":{"date-parts":[[2026,8,5]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.6c05240","relation":{},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]}}}