{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:43:45Z","timestamp":1778575425871,"version":"3.51.4"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-20100020209"],"award-info":[{"award-number":["NRF-20100020209"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2015R1D1A1A01057200"],"award-info":[{"award-number":["NRF-2015R1D1A1A01057200"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2014-011165"],"award-info":[{"award-number":["NRF-2014-011165"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Chemical Record"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The chemistry of hydrogen cyanide adducts of imines is well\u2010developed, but that of cyanide adducts remains unexplored. This is presumably because these cyanide adducts are not stable and thus not readily available in their isolated forms. In this personal account, we present the progress made in our research program towards the development of novel organic transformations utilizing cyanide adducts of imines as key intermediates. We also report the application of these methodologies to the total synthesis of natural products including indole alkaloids.<\/jats:p>","DOI":"10.1002\/tcr.201800005","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T19:28:10Z","timestamp":1523993290000},"page":"1474-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Chemistry of Cyanide Adducts of Aldimines from Aniline Derivatives"],"prefix":"10.1002","volume":"18","author":[{"given":"Eunjoon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Chemistry Korea University  145 Anam-ro, Seongbuk-gu Seoul 02841 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiye","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Chemistry Korea University  145 Anam-ro, Seongbuk-gu Seoul 02841 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheol\u2010Hong","family":"Cheon","sequence":"additional","affiliation":[{"name":"Department of Chemistry Korea University  145 Anam-ro, Seongbuk-gu Seoul 02841 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"For reviews on the Strecker reaction see:"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr200057t"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.3998\/ark.5550190.p008.487"},{"key":"e_1_2_8_4_1","unstructured":"For reviews on other applications of Strecker products towards the umpolung reactivity of aldimines involving the \u03b1-deprotonation of Strecker products with a stoichiometric amount of a strong base see:"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1039\/a908290e"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1216839"},{"key":"e_1_2_8_7_1","unstructured":"\u00a0"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)86145-7"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200501705"},{"key":"e_1_2_8_10_2","first-page":"945","author":"Meyer N.","year":"2005","journal-title":"Synthesis"},{"key":"e_1_2_8_11_1","unstructured":"For reviews on the synthesis of benzoxazoles see:"},{"key":"e_1_2_8_12_2","volume-title":"Comprehensive Heterocyclic Chemistry III","author":"Katritzky A. R.","year":"2008"},{"key":"e_1_2_8_13_2","volume-title":"Handbook of Heterocyclic Chemistry","author":"Katritzky A. R.","year":"2000"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr300527g"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201200684"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/c39760000734"},{"key":"e_1_2_8_17_1","unstructured":"When a mixture of 2-aminophenol and benzaldehyde was treated with a catalytic amount of cyanide the yield of benzoxazole was lower than that obtained from the isolated aldimine. This could be attributed to the formation of side reactions of aldehyde under these reaction conditions such as dimerization (benzoin condensation) and trimerization. For studies on the trimerization of aldehyde in the presence of cyanide see:"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol5008845"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/bkcs.10398"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2013.05.138"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo4021908"},{"key":"e_1_2_8_22_1","unstructured":"Later our group developed protocols for the synthesis of benzimidazoles from 1 2-phenylenediamines and aldehydes using either water or iodide as the nucleophilic catalyst. For details see:"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2014.12.043"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201500302"},{"key":"e_1_2_8_25_1","unstructured":"We also investigated significant differences in the reaction pathways with cyanide between aldimines from 2-aminophenols1and 2-aminothiophenols7and those from 1 2-phenylenediamines9. Particularly we considered the possibility of 6-membered ring formation from cyanide adductsI\u2013CNof aldimines derived fromortho-aminophenols1andortho-aminothiophenols7. Since both transition states for 5-exo-tet and 6-exo-dig cyclization could have a strong orbital interaction (orbital stabilization) between the lone pair on the heteroatom and \u03c0-electrons on the phenyl ring both cyclizations from these adductsI\u2013CNwould be possible reaction pathways. However 5-membered ring formation is generally kinetically more favored than 6-membered ring formation and thus we observed the exclusive formation of benzofused azole compounds2and8rather than the corresponding 6-membered benzofused azine compounds."},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo900050k"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)00003-4"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.5b01922"},{"key":"e_1_2_8_29_1","unstructured":"The more popular method to accomplish the umpolung reactivity of aldimines involves the \u03b1-deprotonation of Strecker products with a stoichiometric amount of a strong base. For reviews see ref 2."},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01395a022"},{"key":"e_1_2_8_31_1","unstructured":"\u00a0"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo035245j"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo051102g"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol8012765"},{"key":"e_1_2_8_35_1","unstructured":"For mechanistic studies on the cyanide-catalyzed dimerization of aldimines see:"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)87506-7"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00831a115"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00966a037"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol061617"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201600155"},{"key":"e_1_2_8_41_1","unstructured":"The efficiency of tautomerization of cyanide adducts27should depend on the relative stabilities of adducts27and anionic species28. As thepKavalues of aliphatic protons are considerably higher than those of benzylic protons it was anticipated that the stabilities of carbanions28obtained from aliphatic aldehydes would be much lower than those from aromatic aldehydes. On the other hand thepKavalues of benzylic and allylic protons are similar and it was expected that adducts27from \u03b1 \u03b2-unsaturated aldehydes could undergo proton transfer to generate the umpolung species28. For thepKavalues of benzylic allylic and aliphatic protons see: http:\/\/www.chem.wisc.edu\/areas\/reich\/pkatable\/index.htm."},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.6b01621"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.6b02597"},{"key":"e_1_2_8_44_1","unstructured":"Our studies revealed that aldimines possessing an acidic proton generally require a stoichiometric amount of cyanide to promote the imino-Stetter reaction. Since aldimine36possesses an acidic proton on the quinazolinone ring we performed the same transformation with a stoichiometric amount of cyanide. When36was subjected to the imino-Stetter conditions in the presence of a catalytic amount of cyanide the desired indole product37was obtained in low yield."},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00253a011"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2014.02.065"},{"key":"e_1_2_8_47_1","unstructured":"\u00a0"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2006.06.077"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.08.057"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.7b00687"},{"key":"e_1_2_8_51_1","unstructured":"Most of the previous approaches utilizedortho-functionalized aniline derivatives as the precursor for the amino group in the seven-membered C-ring. Consequently lengthy steps were necessary for preparing aniline derivatives protection\/deprotection of the amino group during its installation in the indole framework and subsequent cyclization."},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1588749"},{"key":"e_1_2_8_53_1","unstructured":"We expected that this synthetic sequence for paullone and its derivatives60would significantly streamline their total syntheses because the direct use of a nitro group as the precursor of the amino group would eliminate the necessity for protection\/deprotection of the amino group. Furthermore 2-nitrobenzaldehyde (63) is commercially available."},{"key":"e_1_2_8_54_1","unstructured":"We believe that the two side-products (64and65) are formed as follows. The cyanide adductB\u2032likely undergoes hydride transfer to form iminonitrile64. Conjugate addition of the resulting hydride to \u03b1 \u03b2-unsaturated ester in aldimine62\u2009aand subsequent addition of the enolate to imine affords dihydroquinoline65."},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7OB02691A"}],"container-title":["The Chemical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Ftcr.201800005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tcr.201800005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/tcr.201800005","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tcr.201800005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T20:08:58Z","timestamp":1694376538000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tcr.201800005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,17]]},"references-count":55,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/tcr.201800005"],"URL":"https:\/\/doi.org\/10.1002\/tcr.201800005","archive":["Portico"],"relation":{},"ISSN":["1527-8999","1528-0691"],"issn-type":[{"value":"1527-8999","type":"print"},{"value":"1528-0691","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,17]]},"assertion":[{"value":"2018-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}