Asymmetric synthesis of cis-2-substituted cyclohexanamines with high optical purity

Asymmetric reductive amination of racemic 2-substituted cyclohexanones (R= methyl, ethyl, phenyl, benzyl) using optically active 1-phenyl-ethylamines yields optically active cis-cyclohexanamines.     

Selective Reductive Elimination at Alkyl Palladium(IV) by Dissociative Ligand Ionization: Catalytic C(sp3)−H Amination to Azetidines

A palladium(II)‐catalyzed γ‐C?H amination of cyclic alkyl amines to deliver highly substituted azetidines is reported. The use of a benziodoxole tosylate oxidant in combination with AgOAc was found to be crucial for controlling a selective reductive elimination pathway to the azetidines. The process is tolerant of a range of functional groups, including structural features derived from chiral α‐amino alcohols, and leads to the diastereoselective formation of enantiopure azetidines.     

Chelation controlled reductive amination of cyclic ketones to trans-4-methoxycyclohexylamines: 9-BBN reduction mediated with FeCl3

A novel trans-diastereoselective reductive amination of 4-substituted cyclohexanones is described using 9-BBN as reducing agent in the presence of FeCl₃. The method permits efficient synthesis of structurally diverse 4-trans-alkoxycyclohexylamines.     

Synthesis of substituted 5-aminomethyl tetrahydro-isoquinolines and dihydro-isoindoles

The synthesis of ten substituted aminomethylene tetrahydro-isoquinolines is described, proceeding in eight steps from 5-hydroxyisoquinoline via reductive amination of N-Boc tetrahydro-isoquinoline 5-carboxaldehyde. Likewise, reductive amination was used to prepare four substituted dihydro-isoindoles from the corresponding aldehyde. The dihydro-isoindole ring system was conveniently accessed via a 2+2+2 cycloaddition reaction.     

Selective Ruthenium‐Catalyzed Reductive Alkoxylation and Amination of Cyclic Imides

Reported herein, for the first time, is the selective ruthenium‐catalyzed reductive alkoxylation and amination of phthalimides/succinimides. Notably, this novel methodology avoids hydrogenation of the aromatic ring and allows methoxylation of substituted imides with good to excellent selectivity for one of the carbonyl groups. The reported method opens the door to the development of new processes for the selective synthesis of various functionalized N‐heterocyclic compounds. As an example, intramolecular reductive couplings to afford tricyclic compounds are presented for the first time.     

Concise synthesis of pyrrolidine and indolizidine alkaloids by a highly convergent three-component reaction

The synthesis of pyrrolidine and indolizidine derivatives through radical carboazidation of alkenes with α-iodoketones, followed by reductive amination, is described. When properly substituted, further lactamization afforded pyrrolizidinones in good yield. This carboazidation/reductive amination sequence was efficiently applied to the total synthesis of three different simple alkaloids, including (±)-monomorine I.     

Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and Mechanistic Insights

Bi(NO₃)₃·5H₂O‐Catalyzed redox amination scope and mechanistic insights of benzylic ketones with indoline are discussed. The experimental results demonstrate that the formation of N‐alkyl‐substituted indole/indoline derivatives over typically competitive redox and reductive amination processes is depending upon the reaction condition for the benzylic ketones.     

Ruthenium‐Catalyzed Direct Asymmetric Reductive Amination of Diaryl and Sterically Hindered Ketones with Ammonium Salts and H2

A Ru‐catalyzed direct asymmetric reductive amination of ortho‐OH‐substituted diaryl and sterically hindered ketones with ammonium salts is reported. This method represents a straightforward route toward the synthesis of synthetically useful chiral primary diarylmethylamines and sterically hindered benzylamines (up to 97 % yield, 93–>99 % ee). Elaborations of the chiral amine products into bioactive compounds and a chiral ligand were demonstrated through manipulation of the removable and convertible ‐OH group.     

Synthesis of N-Benzyl Allylamnes by Reductive Amination with Selenophenol Generated Catalytically

A convenient method for the preparation of N-Benzyl allylamines is described. Selenophenol generated in catalytic quantities from diphenyldiselenide and sodium borohydride leads to the reductive amination of allylamine by substituted benzaldehydes.     

General Synthesis of 1‐Substituted 2‐Methylbenzimidazoles from Ketones and 2‐Aminoacetanilide

A novel method for preparation of 1‐substituted benzimidazoles via reductive amination of ketones with N‐differentiated 1,2‐diaminobenzenes is described. The method appears to be general in application to acyclic and cyclic ketones, as well as heteroatom‐substituted cyclic ketones.     

Hydrogen bond catalyzed direct reductive amination of ketones

[reaction: see text] A novel, biomimetic concept for the direct reductive amination of ketones is described that relies on selective imine activation by hydrogen bond formation. The mild, acid- and metal-free process requires only catalytic amounts of thiourea as hydrogen bond donor and utilizes the Hantzsch ester for transfer hydrogenation. The method allows the efficient synthesis of structurally diverse amines.     

Efficient Synthesis of Thalifoline and Its Analogs

Thalifoline (1) and its analogs were synthesized from methyl 3-hydroxy-4-methoxy benzoate by prenyl etherification, Claisen rearrangement, oxidation, imine formation, reductive amination and intramolecular amidation. The last three steps, imine formation, reductive amination, and intramolecular amidation, were completed in one pot at room temperature.     

Reductive Amination of Aldehydes and Amines with an Efficient Pd/NiO Catalyst

By applying a simple Pd/NiO catalyst, the reductive amination of amines and aldehydes can progress efficiently under mild reaction conditions, and 24 substituted amines with different structures were synthesized with up to 98% isolated yields.     

Synthesis of pentahydroxy indolizidine alkaloids using ring closing metathesis: attempts to find the correct structure of uniflorine A

Ring closing metathesis of d-glucose derived diene-substrate containing nitrogen functionality followed by asymmetric dihydroxylation afforded sugar substituted dihydroxylated pyrrolidines 8a-c which on 1,2-acetonide deprotection and reductive amination afforded putative uniflorine A 2a and its analogues 2b-c, respectively.     

Preparative synthesis of heterocyclic and aromatic N-benzyl amines

A simple and highly efficient procedure has been proposed for the synthesis of heterocyclic and aromatic N-benzyl amines via reductive amination of substituted aromatic aldehydes in the presence of sodium tetrahydridoborate-acetic acid system generating reactive sodium triacetoxyhydridoborate.     

Comparison of different reducing systems in the synthesis of functionally substituted benzylamines from alkyl aryl ketones and aromatic aldehydes

Different synthetic approaches to functionally substituted benzylamines were examined: reductive amination of alkyl aryl ketones and reduction of aromatic aldehyde oximes. The most efficient procedures were used to prepare a series of previously unknown hydroxy-, alkoxy-, and halogen-substituted benzylamines.     

A new route to 1,4-oxazepanes and 1,4-diazepanes from Garner aldehyde

A highly efficient and convenient method for the synthesis of substituted chiral 1,4-oxazepanes and 1,4-diazepanes have been described from Garner aldehyde through reductive amination with amino ester hydrochlorides followed by intramolecular cyclization as the key steps.     

Synthesis of diazadibenzo‐18‐crown‐6 ligands with appended chromophoric and fluorophoric groups as potential metal ion chemosensors

Six new diazadibenzo‐18‐crown‐6 ligands substituted with two each of 8‐hydroxyquinoline (7), 8‐amino‐quinoline (attached through its C‐2 or C‐7 position) ( 12 and 13 ), 8‐methoxyquinoline ( 18 ), 5‐chloro‐8‐methoxyquinoline ( 19 ), and dansylamidoethyl ( 21 ) side arms were synthesized as potential metal ion chemosensors and potential reagents for the selective extraction of certain metal ions from aqueous solutions. Ligands 7, 12, 13, 18 , and 19 were synthesized by reductive amination of diazadibenzo‐18‐crown‐6 ( 5 ) and the appropriate quinolinecarboxaldehydes. Bis(dansylamidoethyl)‐substituted ligand 21 was synthesized by treating diazacrown ether 5 with N‐dansylaziridine ( 20 ).     

Synthesis of bicyclic azacompounds (3‐dimethylcarbamoyloxyphenyl) substituted as acetylcholinesterase inhibitors

This paper describes the synthesis of some bicyclic 2‐(3‐dimethylcarbamoyloxyphenyl) substituted azaderivatives, obtained from 1,4‐ and 1,5‐diketones, which were cyclized with ammonium acetate, methylamine and by reductive amination. Corresponding 3‐substituted derivatives were instead prepared by reaction of 1,5‐ketoesters with formamide. The carbamates were tested as in vitro acetylcholinesterase inhibitors.     

Hydroformylation of alkenylamines. Concise approaches toward piperidines, quinolizidines, and related alkaloids

Linear hydroformylation of N-protected allyl- or homoallylamines (cyclohydrocarbonylation: CHC), followed by a reductive amination constitute the two key steps toward convenient routes to aza-heterocycles.