{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T01:54:38Z","timestamp":1776304478618,"version":"3.50.1"},"reference-count":108,"publisher":"Wiley","issue":"46","license":[{"start":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T00:00:00Z","timestamp":1539907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01-124295A"],"award-info":[{"award-number":["R01-124295A"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2018,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Even though there are dozens of biologically active 2\u2010substituted and 2,6\u2010disubstituted piperidines, only a limited number of approaches exist for their synthesis. Herein is described two Mannich\u2010type additions to nitrones, one using \u03b2\u2010ketoacids under catalyst\u2010free conditions and another using methyl ketones in the presence of chiral thioureas, which can generate a broad array of such 2\u2010substituted materials, as well as other ring variants, in the form of \u03b2\u2010<jats:italic>N<\/jats:italic>\u2010hydroxy\u2010aminoketones. Both processes have broad scope, with the latter providing products with high enantioselectivity (up to 98\u2009%). The combination of these methods, along with other critical steps, has enabled 8\u2010step total syntheses of the 2,6\u2010disubstituted piperidine alkaloids (\u2212)\u2010lobeline and (\u2212)\u2010sedinone.<\/jats:p>","DOI":"10.1002\/anie.201809799","type":"journal-article","created":{"date-parts":[[2018,10,2]],"date-time":"2018-10-02T00:51:22Z","timestamp":1538441482000},"page":"15162-15166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Mannich\u2010type Reactions of Cyclic Nitrones: Effective Methods for the Enantioselective Synthesis of Piperidine\u2010containing Alkaloids"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4406-8440","authenticated-orcid":false,"given":"Vladislav G.","family":"Lisnyak","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Chicago  5735 S. Ellis Avenue Chicago IL 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8321-4239","authenticated-orcid":false,"given":"Tessa","family":"Lynch\u2010Colameta","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Chicago  5735 S. Ellis Avenue Chicago IL 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3594-8769","authenticated-orcid":false,"given":"Scott A.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Chicago  5735 S. Ellis Avenue Chicago IL 60637 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,19]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-8210(96)80026-4"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1039\/B612166G"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1039\/a707613d"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm501100b"},{"key":"e_1_2_2_6_1","unstructured":"\u00a0"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1139\/v51-040"},{"key":"e_1_2_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cber.19590920502"},{"key":"e_1_2_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)85263-1"},{"key":"e_1_2_2_10_2","doi-asserted-by":"publisher","DOI":"10.1139\/v83-083"},{"key":"e_1_2_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/np970541a"},{"key":"e_1_2_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(04)01294-3"},{"key":"e_1_2_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.5b00801"},{"key":"e_1_2_2_14_1","unstructured":"\u00a0"},{"key":"e_1_2_2_15_2","doi-asserted-by":"publisher","DOI":"10.1139\/v67-208"},{"key":"e_1_2_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00173a025"},{"key":"e_1_2_2_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2012.00239"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol2017406"},{"key":"e_1_2_2_19_1","unstructured":"For selected examples of intramolecularaza-Michael reactions see:"},{"key":"e_1_2_2_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo800749t"},{"key":"e_1_2_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201101292"},{"key":"e_1_2_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201800567"},{"key":"e_1_2_2_22_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201800567"},{"key":"e_1_2_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201805020"},{"key":"e_1_2_2_23_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201805020"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja308872z"},{"key":"e_1_2_2_25_1","unstructured":"\u00a0"},{"key":"e_1_2_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)96130-6"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00293a013"},{"key":"e_1_2_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(96)01266-X"},{"key":"e_1_2_2_29_1","unstructured":"\u00a0"},{"key":"e_1_2_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)78275-X"},{"key":"e_1_2_2_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00120a016"},{"key":"e_1_2_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)01222-9"},{"key":"e_1_2_2_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.5b02029"},{"key":"e_1_2_2_34_1","unstructured":"\u00a0"},{"key":"e_1_2_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/cber.19691020405"},{"key":"e_1_2_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)89124-9"},{"key":"e_1_2_2_37_1","unstructured":"For reviews see:"},{"key":"e_1_2_2_38_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-6269"},{"key":"e_1_2_2_39_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1260979"},{"key":"e_1_2_2_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201300465"},{"key":"e_1_2_2_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201700986"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlac.19596260115"},{"key":"e_1_2_2_43_1","unstructured":"\u00a0"},{"key":"e_1_2_2_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/recl.19640831209"},{"key":"e_1_2_2_45_2","doi-asserted-by":"publisher","DOI":"10.1039\/p19820002477"},{"key":"e_1_2_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4020(95)00667-W"},{"key":"e_1_2_2_47_1","unstructured":"Similar reactions usually require a catalyst or promoter:"},{"key":"e_1_2_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2013.06.030"},{"key":"e_1_2_2_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.6b01750"},{"key":"e_1_2_2_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.8b01422"},{"key":"e_1_2_2_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201201644"},{"key":"e_1_2_2_52_1","unstructured":"\u00a0"},{"key":"e_1_2_2_53_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1974-23294"},{"key":"e_1_2_2_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00232a006"},{"key":"e_1_2_2_55_1","unstructured":"For recent reviews see:"},{"key":"e_1_2_2_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr0684016"},{"key":"e_1_2_2_57_2","doi-asserted-by":"publisher","DOI":"10.1039\/b903816g"},{"key":"e_1_2_2_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200390042"},{"key":"e_1_2_2_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(03)00433-7"},{"key":"e_1_2_2_60_1","unstructured":"For selected recent reviews see:"},{"key":"e_1_2_2_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr068373r"},{"key":"e_1_2_2_62_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3ob41403e"},{"key":"e_1_2_2_63_1","unstructured":"\u00a0"},{"key":"e_1_2_2_64_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol9010322"},{"key":"e_1_2_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetasy.2009.06.003"},{"key":"e_1_2_2_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200905313"},{"key":"e_1_2_2_66_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200905313"},{"key":"e_1_2_2_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol1005104"},{"key":"e_1_2_2_68_1","unstructured":"\u00a0"},{"key":"e_1_2_2_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja028353g"},{"key":"e_1_2_2_70_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0620890"},{"key":"e_1_2_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2009.05.036"},{"key":"e_1_2_2_72_1","unstructured":"The structural assignment of33was confirmed after N-O reductive cleavage (see SI for details)."},{"key":"e_1_2_2_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201402859"},{"key":"e_1_2_2_74_1","unstructured":"\u00a0"},{"key":"e_1_2_2_75_2","doi-asserted-by":"publisher","DOI":"10.1039\/j39680002423"},{"key":"e_1_2_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)89025-6"},{"key":"e_1_2_2_77_1","unstructured":"At this stage the optical rotation and thus absolute configuration of31 was confirmed after reductive cleavage of the N\u2212O bond (see SI for details)."},{"key":"e_1_2_2_78_1","unstructured":"\u00a0"},{"key":"e_1_2_2_79_2","doi-asserted-by":"publisher","DOI":"10.1039\/b706793c"},{"key":"e_1_2_2_80_2","doi-asserted-by":"publisher","DOI":"10.1021\/cs5006037"},{"key":"e_1_2_2_81_1","unstructured":"\u00a0"},{"key":"e_1_2_2_82_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00904147"},{"key":"e_1_2_2_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlac.19576080111"},{"key":"e_1_2_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetasy.2008.02.019"},{"key":"e_1_2_2_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200803647"},{"key":"e_1_2_2_85_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200803647"},{"key":"e_1_2_2_86_1","unstructured":"\u00a0"},{"key":"e_1_2_2_87_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo981912a"},{"key":"e_1_2_2_88_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo020501y"},{"key":"e_1_2_2_89_2","unstructured":"F.-D.Klingler R.Sobotta U.S. Patent 2006014791 2006;"},{"key":"e_1_2_2_90_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol071064i"},{"key":"e_1_2_2_91_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja804738b"},{"key":"e_1_2_2_92_1","doi-asserted-by":"publisher","DOI":"10.1139\/v91-034"},{"key":"e_1_2_2_93_1","unstructured":"\u00a0"},{"key":"e_1_2_2_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00899-1"},{"key":"e_1_2_2_95_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0501228"},{"key":"e_1_2_2_96_1","doi-asserted-by":"publisher","DOI":"10.1080\/00397919108055456"},{"key":"e_1_2_2_97_1","unstructured":"\u00a0"},{"key":"e_1_2_2_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(80)80010-4"},{"key":"e_1_2_2_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)60077-1"},{"key":"e_1_2_2_100_1","unstructured":"This value was established at the final stage whenepi-4was isolated as the major product."},{"key":"e_1_2_2_101_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo048848j"},{"key":"e_1_2_2_102_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b07024"},{"key":"e_1_2_2_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2007.08.092"},{"key":"e_1_2_2_104_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4OB01787K"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fanie.201809799","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201809799","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.201809799","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201809799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T12:53:09Z","timestamp":1694695989000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.201809799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,19]]},"references-count":108,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2018,11,12]]}},"alternative-id":["10.1002\/anie.201809799"],"URL":"https:\/\/doi.org\/10.1002\/anie.201809799","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,19]]},"assertion":[{"value":"2018-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}