Protecting‐Group‐Free Synthesis of Natural Products and Analogs, Part I. Lewis Acid‐Catalyzed Reductive Amination of Aldehydes and Ketones with N,N‐Dimethylformamide as Dimethylamino Source, Reductant and Solvent. Iminosugars 22 and 23 were obtained in excellent yields (85–99 %) and high diastereoselectivity (only β‐isomer). She is currently completing her PhD in Organic Synthesis under the supervision of Prof. F. Cardona at the University of Florence since 2017, where she is working on the synthesis and biological evaluation of nitrogen‐containing carbohydrate mimetics as potential Pharmacological Chaperones for lysosomal storage diseases in collaboration with Meyer's Children Hospital (Prof. A. Morrone). The reaction allowed the one‐pot synthesis of the major azide 129a in good yield (67 %). Electronic Supporting Information files are available without a subscription to ACS Web Editions. Compounds 116 and 117 revealed more potent inhibitors of β‐glucosidase (IC50 = 3.18 µm and 4.97 µm, respectively), than 115 (IC50 = 1.40 mm), showing that either inversion of configuration at C‐4 or substitution of an OH group with a hydroxyethyl functionality resulted in increased potency towards β‐glucosidase with high specificity.38, Fleet and co‐workers exploited the kinetic and thermodynamic azide displacement of sugar‐derived triflates to access azido‐γ‐lactones as key intermediates in the synthesis of homonojirimycin (HNJ) analogues, employing a biotechnological approach via the Izumoring techniques.39. The process is catalyzed by pyridoxamine phosphate, which is converted into pyridoxal phosphate after the reaction. Learn about our remote access options, The R. W. Johnson Pharmaceutical Research Institute, Drug Discovery Division, Spring House, Pennsylvania, 19477. We use cookies to help provide and enhance our service and tailor content and ads. Aldehyde 127 was accessed in four steps from d‐mannose on gram scale. A classic named reaction is the Mignonac reaction (1921)[8] involving reaction of a ketone with ammonia over a nickel catalyst for example in a synthesis of 1-phenylethylamine starting from acetophenone:[9], Nowadays, one-pot reductive amination fulfil by acid-metal catalysts that act as a hydride transfer. "Nouvelle méthode générale de préparation des amines à partir des aldéhydes ou des cétones",, Creative Commons Attribution-ShareAlike License, This page was last edited on 12 November 2020, at 19:35. Godin and co‐workers synthesized iminosugar C‐glycosides with a great degree of structural diversity via cross‐metathesis reactions of N‐protected α‐1‐C‐allyl‐1‐deoxynojirimycin derivatives and a large series of different alkenes.27 Condensation of aldehyde 24 with 2‐naphthalenemethylamine (NAPNH2) followed by reaction with allylmagnesium bromide gave the diastereomerically pure amine 29 (Scheme 7). The N‐naphthalenemethyl protective group was selectively and efficiently removed and the resulting secondary amine 31 was formylated or protected with a Troc group. Catalytic Direct α-Amination of Arylacetic Acid Synthons with Anilines. The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. A Staudinger aza‐Wittig reaction performed on 90 afforded partially protected cyclic imine 91.33 The latter was subjected to diastereoselective (de > 98 %) addition of Grignard reagents, which afforded the corresponding aza‐C‐α‐mimetics 92 in good yield (85–95 %) after acetonide deprotection with TFA. Department of Chemistry, University at Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, United States, Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, DE-70569 Stuttgart, Germany, Intramolecular Pd-Catalyzed Reductive Amination of Enolizable sp. of CH3COOH, affording piperidines 138 and 142 with excellent yields. These aspects are particularly important in the development of industrial processes for the more therapeutically appealing compounds. [4][5] Possibly the reaction proceeds via reduction of the hemiaminal species.[6]. The equilibrium between aldehyde/ketone and imine can be shifted toward imine formation by removal of the formed water through physical or chemical means. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, By continuing to browse this site, you agree to its use of cookies as described in our, I have read and accept the Wiley Online Library Terms and Conditions of Use. Worth Publishing: New York, 2000. Use the link below to share a full-text version of this article with your friends and colleagues. Reductive amination Reaction type Coupling reaction … Reductive amination is an important tool for synthetic organic chemists in the construction of carbon‐nitrogen bonds. [30] Moreover, compound 58 was found to inhibit α‐fucosidase (Ki = 8.4 µm). A Direct Organocatalytic Entry to Selectively Protected Aldopentoses and Derivatives. Biocatalytic Production of Amino Carbohydrates through Oxidoreductase and Transaminase Cascades. Formal α-Allylation of Primary Amines by a Dearomative, Palladium-Catalyzed Umpolung Allylation of -Substituted 3-Amino-4-halopyridines: A Sequential Boc-Removal/Reductive Amination Mediated by Brønsted and Lewis Acids Reductive amination is an important tool for synthetic organic chemists in the construction of carbon‐nitrogen bonds. For reproduction of material from all other RSC journals. In order to investigated the glycosidase inhibition profiles of the enantiomers of the naturally occurring glycosidase inhibitors (the so‐called “looking glass inhibitors”), Fleet and co‐workers reported a convenient large‐scale synthesis of 1,6‐dideoxygalactostatin 97 (d‐DFJ), the enantiomer of the potent fucosidase inhibitor deoxyfuconojirimycin (l‐DFJ), from the readily available 2,3‐O‐isopropylidene‐d‐gulonolactone, in five steps and 54 % overall yield.36 The straightforward synthesis involved introduction of azide moiety through sulfonylation of the free hydroxy group in compound 93 with trifluoromethanesulfonic anhydride in dichloromethane, followed by nucleophilic displacement of the resulting triflate with sodium azide in DMF to afford the corresponding azidolactone 94 (Scheme 13). The first example of an intramolecular asymmetric reductive amination of a dialkyl ketone with an aliphatic amine has been developed for the synthesis of Suvorexant (MK-4305), a potent dual Orexin antagonist under development for the treatment of sleep disorders.