Direct Reductive Amination with Amine Boranes

mentioning

confidence: 99%

A Safe and Scalable Procedure for Preparation of α-Picoline–Borane from Sodium Mono-acyloxyborohydrides and α-Picoline

Kawase

Yamagishi

Kutsuma

et al. 2012

“…As we expected, excess amount of NaBH(OAc) 3 was required in MeOH solvent; however, the desired product was obtained without decomposition. On the contrary, an alkyl amine/borane complex such as 5-ethyl-2-methylpyridine/borane, triethylamine/borane, or t -BuNH 2 /borane did not give a good reaction profile (entries 4–6). Fortunately, the borane complex with a relatively weak base such as the pyridine/borane complex or the 2-picoline/borane complex in MeOH gave excellent results; the desired compound was obtained without decomposition in good yield, more than 90% as an HCl salt.…”

Section: Results and Discussionmentioning

confidence: 99%

A Challenging Synthesis of the Highly Functionalized Echinocandin ASP9726: A Successor of Micafungin

Yoshida

Hayashida

Morinaga

et al. 2014

Here, we describe a practical, scalable, and challenging synthesis of the highly functionalized novel echinocandin ASP9726 (1) starting from the natural product FR901379 (3), which is a starting material of micafungin (2). The synthesis includes transformations that address significant synthetic challenges due to the need to control the chemoselectivity of the reactions during modification of the highly functionalized peptide core. In the present study, we discovered an efficient, highyielding route to ASP9726 (1) that is suitable for large-scale production. Namely, dehydration of carboxamide ( 14) to nitrile (15) was accomplished by use of EDC•HCl with pyridine. Further, the transformation of nitrile (15) to primary amine (17) was conducted via hydrogenation with Sponge Nickel catalyst without decomposition, followed by one-pot debenzylation with Pd/C. Reductive amination between primary amine (17) with dihydroxyacetone (DHA) was accomplished using 2-picoline/borane complex as a reducing agent in MeOH, yielding 66.6 kg of peptide core unit (18). After the C 15 H 31 chain cleavage by bioconversion, reductive amination between the core peptide unit (4) and side chain (10) was achieved in high yield by making use of tert-butyl amine/borane complex as a reducing agent. Consequently, highly pure ASP9726 (1) was obtained in a practical manner without using silica gel or ODS column chromatography purification in any step. Overall yield was drastically increased from 0.71% to 13.8% compared to that of the prior synthetic method.

“…Among the reagents used in reductive amination, amineboranes have several advantageous properties, such as stability in the presence of water and mildly acidic conditions, as well as selective reduction of an imine in the presence of a carbonyl. 24 Although other reagents such as sodium cyanoborohydride (NaBH 3 CN) 26 and sodium triacetoxyborohydride (STAB) 27 have many of these same properties, they have several disadvantages compared to amine-boranes. NaBH 3 CN (i) is often used in excess, (ii) reacts slowly, and (iii) can release toxic byproducts.…”

Section: Introductionmentioning

confidence: 99%

“…Amine-boranes have also been applied to the reactions characteristic of many boron hydride reagents, such as organic reduction, , hydroboration, , and reductive amination. , The importance of reductive amination for the preparation of structurally diverse amines present in natural products, pharmaceutical agents, and synthetic intermediates has made it one of the key reactions in organic chemistry. Among the reagents used in reductive amination, amine-boranes have several advantageous properties, such as stability in the presence of water and mildly acidic conditions, as well as selective reduction of an imine in the presence of a carbonyl . Although other reagents such as sodium cyanoborohydride (NaBH 3 CN) and sodium triacetoxyborohydride (STAB) have many of these same properties, they have several disadvantages compared to amine-boranes.…”

Section: Introductionmentioning

confidence: 99%

Scalable, Green Synthesis of Heteroaromatic Amine-boranes

Ramachandran

Hamann

Lin

et al. 2023

In situ generated, transient sodium monohydroxyborohydride readily reacts with a present amine to form amine-borane adducts in ethyl acetate at room temperature. Synthesis of heteroaromatic pyridine-, 2-picoline-, and 5-ethyl-2-methylpyridine-boranes, those relevant to large-scale reductive aminations, has been demonstrated at 100 mmol scale, and pyridine-borane at 1.1 mole scale. This first report substituting ethyl acetate for tetrahydrofuran, the traditional solvent for amine-borane synthesis, allows for activation of sodium borohydride by the aqueous portion of the heterogeneous dual-solvent system. These factors make this green protocol more economical than those currently available for the large-scale production of amine-boranes as demonstrated, quantitatively, by the computed green chemistry metrics.