Reductive Amination/Cyclization of Keto Acids Using a Hydrosilane for Selective Production of Lactams versus Cyclic Amines by Switching of the Indium Catalyst

Abstract

Described herein is that the catalytic construction of N-substituted five- and six-membered lactams from keto acids with primary amines by reductive amination, using an indium/silane combination. This relatively benign and safe catalyst/reductant system tolerates the use of a variety of functional groups, especially ones that are reduction-sensitive. A direct switch from synthesizing lactams to synthesizing cyclic amines is achieved by changing the catalyst from In(OAc)3 to InI3. This conversion occurs by further reduction of the lactam using the indium/silane pair.

A Facile Direct Route to N‐(Un)substituted Lactams by Cycloamination of Oxocarboxylic Acids without External Hydrogen

“…These findings demonstrate that water obtained by LA dehydration can in principle promote the hydrolysis of H 2 NCHO and relevant N-formyl intermediates to releaseH COOH. [11] Our method showss uperior performance in terms of the reaction rate with and without HCOOH( 1227 and 470 mmol h À1 ;T able 1, entries 3a nd 4) while affordingg ood lactam yields that are comparable to previously reported results (entries3-11). It is worth notingt hat the reaction withoutH COOH exhibits superior green chemistry metrics, including ah igh reaction mass efficiency (RME),alow E-factor, and good atom economy compared to the case with HCOOH( Ta ble S2).…”

“…To explore this opportunity,s everalc ontrole xperiments were conducted. [5][6][7][8][9][10][11]. [16] Second, H 2 NCHO can be hydrolyzed in water with conversions up to around7 0% after 1.5 ha t1 60 8Ca nd were then constant upon prolonged reactiont o4h.…”

“…[16] Second, H 2 NCHO can be hydrolyzed in water with conversions up to around7 0% after 1.5 ha t1 60 8Ca nd were then constant upon prolonged reactiont o4h. Ta ble 1s hows that systemsd epending on metal catalysts require much longer reaction times (up to 72 h) to achieve moderate yields of either substituted or unsubstitutedl actams (entries [8][9][10][11], despite relativelyl ow reaction temperatures (25-130 8C). As expected, the addition of water (30 equiv) into the reactions ystemsw ith and withoutH COOH ( Table 1, entries 3a nd 4) significantly acceleratest he cycloamination reaction, providing comparable MPD yields of 92 and 94 %.…”

“…Ap rime examplei sl evulinic acid (LA), whichc an be easily obtained from renewable lignocellulosic biomass. [11][12][13] Significant progress has been made in the selective production of N-substituted lactamsa nd pyrrolidones from LA (see the Supporting Information, Ta ble S1), but in all cases the use of an organic solvent, ane xternal hydrogen source, and/or additives are key to obtain good results. [11] In connection with this, various strategies have recently been proposed to design and prepare catalysts with uniquef unctionalities for simplifying the overall process, such as the use of low-pressure hydrogen, or hydrogen-donating co-reactants such as formic acid (HCOOH) and hydrosilanes under mild conditions.…”

A Multiphase Protocol for Selective Hydrogenation and Reductive Amination of Levulinic Acid with Integrated Catalyst Recovery

“…Such ad ramatic change was ascribed to concurrent effectsi nferred by examining the accepted mechanismsf or catalytic reductive amination, [31,33,34,38] and comparing the structures of co-products designated as "others" in Table 2. Such ad ramatic change was ascribed to concurrent effectsi nferred by examining the accepted mechanismsf or catalytic reductive amination, [31,33,34,38] and comparing the structures of co-products designated as "others" in Table 2.…”