{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:50:58Z","timestamp":1785351058211,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Herbert C. Brown Center for Borane Research of Purdue University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, the successful titanium tetrachloride-catalyzed reduction of aldehydes, ketones, carboxylic acids, and nitriles with borane\u2013ammonia was extended to the reduction (deoxygenation) of a variety of aromatic and aliphatic pri-, sec- and tert-carboxamides, by changing the stoichiometry of the catalyst and reductant. The corresponding amines were isolated in good to excellent yields, following a simple acid\u2013base workup.<\/jats:p>","DOI":"10.3390\/molecules28124575","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T02:57:30Z","timestamp":1686020250000},"page":"4575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Titanium-Mediated Reduction of Carboxamides to Amines with Borane\u2013Ammonia"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5240-3018","authenticated-orcid":false,"given":"P. 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Org. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1055\/s-0036-1589144","article-title":"Recent Advances in Amide Reductions","volume":"50","author":"Chardon","year":"2018","journal-title":"Synthesis"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ricci, A. (2008). Amino Group Chemistry\u2014From Synthesis to the Life Sciences, Wiley-VCH.","DOI":"10.1002\/9783527621262"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14181","DOI":"10.1021\/acs.chemrev.6b00486","article-title":"Biobased amines: From synthesis to polymers; present and future","volume":"116","author":"Froidevaux","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_6","unstructured":"Roose, P.E.K., Henkes, E., Rossbacher, R., and H\u00f6ke, H. (2015). Ullmann\u2019s Encyclopedia of Industrial Chemistry, Wiley-VCH."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Morrison, A.L., Long, R.F., and Konigstein, M. (1951). The reduction of acid amides with lithium aluminum hydride. J. Chem. Soc., 952\u2013955.","DOI":"10.1039\/JR9510000952"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4555","DOI":"10.1016\/S0040-4039(01)88749-9","article-title":"Reduction of organic compounds with sodium borohydride-transition metal salt systems.1. Reduction of organic nitrile, nitro and amide compounds to primary amines","volume":"10","author":"Satoh","year":"1969","journal-title":"Tetrahedron Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1246\/cl.1990.251","article-title":"A novel highly selective reduction of tertiary amides to amines with sodium borohydride-bis(2-bromoethyl)selenium dibromide","volume":"19","author":"Akabori","year":"1990","journal-title":"Chem. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1055\/s-0030-1258111","article-title":"Amide Activation by Tf2O: Reduction of Amides to Amines by NaBH4 under Mild Conditions","volume":"2010","author":"Xiang","year":"2010","journal-title":"Synlett"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1016\/S0040-4020(01)81236-9","article-title":"Convenient methods for the reduction of amides, nitriles, carboxylic esters, acids and hydroboration of alkenes using nabh4\/i2 system","volume":"48","author":"Prasad","year":"1992","journal-title":"Tetrahedron"},{"key":"ref_12","first-page":"285","article-title":"Sodium borohydride-boron trifluoride ethereate, a convenient and efficient reagent for the reduction of amides","volume":"33","author":"Sengupta","year":"1994","journal-title":"Ind. J. Chem. B"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1039\/C4QO00317A","article-title":"Simple, versatile, and chemoselective reduction of secondary amides and lactams to amines with the Tf2O-NaBH4 or Cp2ZrHCl-NaBH4 system","volume":"2","author":"Huang","year":"2015","journal-title":"Org. Chem. Front."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1039\/b208464c","article-title":"Reduction of amides with NaBH4 in diglyme at 162 degrees C","volume":"27","author":"Zhu","year":"2003","journal-title":"New J. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1248\/cpb.13.394","article-title":"Reduction of acid amides to amines with sodium borohydride","volume":"13","author":"Yamada","year":"1965","journal-title":"Chem. Pharm. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1080\/00397919708006038","article-title":"Unusual reactivity of zinc borohydride\u2014Reduction of amides to amines","volume":"27","author":"Narasimhan","year":"1997","journal-title":"Synth. Commun."},{"key":"ref_17","unstructured":"Davis, M. (1956). Reduction of amides by lithium borohydride. J. Chem. Soc., 3981\u20133982."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1021\/ja01071a037","article-title":"Diborane as mild reducing agent for conversion of primary, secondary and tertiary amides into corresponding amines","volume":"86","author":"Brown","year":"1964","journal-title":"J. Am. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1021\/jo00945a015","article-title":"Selective reductions.18. Fast reaction of primary, secondary, and tertiary amides with diborane\u2014Simple, convenient procedure for conversion of amides to corresponding amines","volume":"38","author":"Brown","year":"1973","journal-title":"J. Org. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1055\/s-1981-29677","article-title":"Improved procedure for borane-dimethyl sulfide reduction of tertiary and secondary amides in the presence of boron-trifluoride etherate","volume":"12","author":"Brown","year":"1981","journal-title":"Synthesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1080\/00397919108021056","article-title":"Effect of the temperature on the stoichiometry of borane dimethyl sulfide reduction of secondary and tertiary amides","volume":"21","author":"Bonnat","year":"1991","journal-title":"Synth. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8019","DOI":"10.1021\/jacs.0c02446","article-title":"La N(SiMe3)(2) (3)-Catalyzed Deoxygenative Reduction of Amides with Pinacolborane. Scope and Mechanism","volume":"142","author":"Barger","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1039\/D0QO01092H","article-title":"Transition-metal-free catalytic hydroboration reduction of amides to amines","volume":"7","author":"Yao","year":"2020","journal-title":"Org. Chem. Front."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1039\/D1NJ04996H","article-title":"Hydroborative reduction of amides to amines mediated by La(CH2C6H4NMe2-o)(3)","volume":"46","author":"Zhang","year":"2022","journal-title":"New J. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1021\/acs.organomet.1c00120","article-title":"Deoxygenation of Primary Amides to Amines with Pinacolborane Catalyzed by Ca N(SiMe3)(2) (2)(THF)(2)","volume":"40","author":"Yu","year":"2021","journal-title":"Organometallics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115784","DOI":"10.1016\/j.poly.2022.115784","article-title":"Hydroboration of nitriles, esters, and amides catalyzed by simple neosilyllithium","volume":"219","author":"Kumar","year":"2022","journal-title":"Polyhedron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10596","DOI":"10.1039\/D1CC04148G","article-title":"Deoxygenative hydroboration of primary and secondary amides: A catalyst-free and solvent-free approach","volume":"57","author":"Kumar","year":"2021","journal-title":"Chem. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1021\/acs.joc.6b00276","article-title":"Controlled Reduction of Tertiary Amides to the Corresponding Alcohols, Aldehydes, or Amines Using Dialkylboranes and Aminoborohydride Reagents","volume":"81","author":"Bailey","year":"2016","journal-title":"J. Org. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/S0040-4039(97)00127-5","article-title":"N,N-diethylaniline-borane, an efficient reducing agent for reduction of representative functional groups","volume":"38","author":"Salunkhe","year":"1997","journal-title":"Tetrahedron Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5973","DOI":"10.1016\/j.tetlet.2010.09.022","article-title":"Spiroborate catalyzed reductions with N,N-diethylaniline borane","volume":"51","author":"Coleridge","year":"2010","journal-title":"Tetrahedron Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1021\/ol990145e","article-title":"Aminoborohydrides. 11. Facile reduction of N-alkyl lactams to the corresponding amines using lithium aminoborohydrides","volume":"1","author":"Flaniken","year":"1999","journal-title":"Org. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1039\/D2QO01717B","article-title":"In situ generated aminodiborane as a reagent for deoxygenative reduction of carboxamides to amines","volume":"10","author":"Nair","year":"2023","journal-title":"Org. Chem. Front."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1002\/adsc.201801447","article-title":"B(C6F5)(3)-Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane","volume":"361","author":"Pan","year":"2019","journal-title":"Adv. Synth. Catal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14377","DOI":"10.1021\/acsomega.2c01461","article-title":"Aminoboranes via Tandem Iodination\/Dehydroiodination for One-Pot Borylation","volume":"7","author":"Ramachandran","year":"2022","journal-title":"ACS Omega"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16580","DOI":"10.1039\/C4DT02467B","article-title":"Ammonia-mediated, large-scale synthesis of ammonia borane","volume":"43","author":"Ramachandran","year":"2014","journal-title":"Dalton Trans."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.ijhydene.2016.06.231","article-title":"Water-promoted, safe and, scalable preparation of ammonia borane","volume":"42","author":"Ramachandran","year":"2017","journal-title":"Int. J. Hydrog. Energy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1021\/acs.orglett.1c00591","article-title":"Ammonia-borane as a Catalyst for the Direct Amidation of Carboxylic Acids","volume":"23","author":"Ramachandran","year":"2021","journal-title":"Org. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13259","DOI":"10.1021\/acs.joc.2c01744","article-title":"TiCl4-catalyzed hydroboration of ketones with ammonia borane","volume":"87","author":"Ramachandran","year":"2022","journal-title":"J. Org. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8481","DOI":"10.1021\/acs.orglett.2c03326","article-title":"A Safer Reduction of Carboxylic Acids with Titanium Catalysis","volume":"24","author":"Ramachandran","year":"2022","journal-title":"Org. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ramachandran, P.V., and Alawaed, A.A. (2023). Room Temperature Reduction of Titanium Tetrachloride-Activated Nitriles to Primary Amines with Ammonia-Borane. Molecules, 28.","DOI":"10.3390\/molecules28010060"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7810","DOI":"10.1021\/ic700772a","article-title":"Preparation of ammonia borane in high yield and purity, methanolysis, and regeneration","volume":"46","author":"Ramachandran","year":"2007","journal-title":"Inorg. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8593","DOI":"10.1021\/acs.orglett.0c03184","article-title":"Amine-boranes as Dual-Purpose Reagents for Direct Amidation of Carboxylic Acids","volume":"22","author":"Ramachandran","year":"2020","journal-title":"Org. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1021\/ol901111g","article-title":"Secondary Amine Formation from Reductive Amination of Carbonyl Compounds Promoted by Lewis Acid Using the InCl3\/Et3SiH System","volume":"11","author":"Lee","year":"2009","journal-title":"Org. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1002\/cctc.201300338","article-title":"Nickel-Catalysed Reductive Amination with Hydrosilanes","volume":"5","author":"Zheng","year":"2013","journal-title":"Chemcatchem"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1002\/anie.201711467","article-title":"Reductive Amination by Photoredox Catalysis and Polarity-Matched Hydrogen Atom Transfer","volume":"57","author":"Guo","year":"2018","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1002\/cctc.201700400","article-title":"Efficient and Selective Hydrosilylation of Secondary and Tertiary Amides Catalyzed by an Iridium(III) Metallacycle: Development and Mechanistic Investigation","volume":"9","author":"Corre","year":"2017","journal-title":"Chemcatchem"},{"key":"ref_47","first-page":"4874","article-title":"Ru-Catalyzed Transfer Hydrogenation of Nitriles, Aromatics, Olefins, Alkynes and Esters","volume":"10","author":"Alshakova","year":"2018","journal-title":"Chemcatchem"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17579","DOI":"10.1039\/C9DT04111G","article-title":"Hydrogenation and N-alkylation of anilines and imines via transfer hydrogenation with homogeneous nickel compounds","volume":"48","author":"Garcia","year":"2019","journal-title":"Dalton Trans."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1039\/C4RA14808H","article-title":"Reductive amination using a combination of CaH2 and noble metal","volume":"5","author":"Guyon","year":"2015","journal-title":"RSC Adv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1002\/ejoc.202000167","article-title":"Ruthenium Catalyzed N-Alkylation of Cyclic Amines with Primary Alcohols","volume":"2020","author":"Savela","year":"2020","journal-title":"Eur. J. Org. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9381","DOI":"10.1002\/anie.201704199","article-title":"Mild Hydrogenation of Amides to Amines over a Platinum-Vanadium Bimetallic Catalyst","volume":"56","author":"Mitsudome","year":"2017","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5603","DOI":"10.1039\/D3NJ00372H","article-title":"Hydrosilylative reduction of secondary amides to amines catalyzed by geometry-constrained NNN-cobalt complexes","volume":"47","author":"Dong","year":"2023","journal-title":"New J. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/adsc.201200835","article-title":"A Practical Procedure for Reduction of Primary, Secondary and Tertiary Amides to Amines","volume":"355","author":"Reeves","year":"2013","journal-title":"Adv. Synth. 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