Protecting-Group-Free Synthesis of Amines: Synthesis of Primary Amines from Aldehydes via Reductive Amination

2010 ◽  
Vol 75 (16) ◽  
pp. 5470-5477 ◽  
Author(s):  
Emma M. Dangerfield ◽  
Catherine H. Plunkett ◽  
Anna L. Win-Mason ◽  
Bridget L. Stocker ◽  
Mattie S. M. Timmer
Keyword(s):  
Reductive Amination ◽  
Primary Amines ◽  
Protecting Group

scholarly journals 2,3-Diaminopropanols Obtained from d-Serine as Intermediates in the Synthesis of Protected 2,3-l-Diaminopropanoic Acid (l-Dap) Methyl Esters

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1313
Author(s):  
Andrea Temperini ◽  
Donatella Aiello ◽  
Fabio Mazzotti ◽  
Constantinos M. Athanassopoulos ◽  
Pierantonio De Luca ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reductive Amination ◽  
Methyl Esters ◽  
Primary Amines ◽  
Synthetic Approach ◽  
Protecting Group ◽  
Synthetic Strategy ◽  
Crude Product ◽  
Diaminopropanoic Acid ◽  
Acid Labile

A synthetic strategy for the preparation of two orthogonally protected methyl esters of the non-proteinogenic amino acid 2,3-l-diaminopropanoic acid (l-Dap) was developed. In these structures, the base-labile protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) was paired to the p-toluensulfonyl (tosyl, Ts) or acid-labile tert-butyloxycarbonyl (Boc) moieties. The synthetic approach to protected l-Dap methyl esters uses appropriately masked 2,3-diaminopropanols, which are obtained via reductive amination of an aldehyde prepared from the commercial amino acid Nα-Fmoc-O-tert-butyl-d-serine, used as the starting material. Reductive amination is carried out with primary amines and sulfonamides, and the process is assisted by the Lewis acid Ti(OiPr)4. The required carboxyl group is installed by oxidizing the alcoholic function of 2,3-diaminopropanols bearing the tosyl or benzyl protecting group on the 3-NH2 site. The procedure can easily be applied using the crude product obtained after each step, minimizing the need for chromatographic purifications. Chirality of the carbon atom of the starting d-serine template is preserved throughout all synthetic steps.

scholarly journals Methodology development for the synthesis of iminosugars

2021 ◽  
Author(s):  
◽  
Alexander Hunt-Painter
Keyword(s):  
Reductive Amination ◽  
Steric Effects ◽  
Primary Amines ◽  
Equatorial Position ◽  
Protecting Group ◽  
Efficient Synthesis ◽  
Electronic Effects ◽  
Synthetic Methodology ◽  
Methodology Development ◽  
The One

<p>This thesis investigated the development and application of methodology for the synthesis of iminosugars. The first portion of this thesis (Chapters 2 and 3) explored the scope of previously established protecting-group-free Vasella-reductive-amination and I2-mediated carbamate annulation methodology initially developed within the Stocker-Timmer group for the synthesis of pyrrolidines and piperidines from aldose sugars. In this thesis, the Vasella-reductive-amination methodology was extended to include the use of ketose sugars as starting materials, thereby allowing for the synthesis of primary amines directly from in situ formed ketones under protecting-group-free conditions. The scope of the carbamate annulation was then explored, whereby it was determined that both steric and electronic effects appear to affect transition state energies during the annulation reaction. Here, formation of pyrrolidines with the 2,5-trans and 3,4-cis relationships are favoured, however, in circumstances were conflicting electronic- and steric-effects are present, steric-effects dominate thereby favouring the formation of the 2,5-trans product. Using a combination of this Vasella-reductive-amination and carbamate annulation methodology, 2,5-dideoxy-2,5-imino-L-iditol was thus synthesised in 6 steps and 18% overall yield from D-fructose. Next, the same methodology was applied to the synthesis of the promising molecular chaperone 2,5-dideoxy-2,5-imino-D-altritol. Thus, 2,5-dideoxy-2,5-imino-D-altritol was synthesised over 7 steps and in 22% yield from D-tagatose, which is the most efficient synthesis of this iminosugar to date.  The second part of this thesis (Chapters 4 and 5) focused on the optimisation and development of synthetic methodology that would allow for the highly efficient synthesis of a variety of iminosugars including piperidines and azepanes. To this end, modifications to existing synthetic methodology allowed for the rapid synthesis of a variety of iodoglycosides, which are important synthons. Next, reductive amination/cyclisation methodology that allowed for the direct transformation of methyl iodoglycosides or isopropylidene-protected iodoglycosides into iminosugars was developed. As such, the piperidines 1-Deoxynojirimycin, 1-Deoxymannojirimycin (DMJ), L-1-Deoxygalactojirimycin (L-DGJ), and (3R,4r,5S)-piperidine-3,4,5-triol were prepared in 4 steps and good overall yields (44%, 62%, 67%, and 53%, respectively). In the case of DMJ and (3R,4r,5S)-piperidine-3,4,5-triol, these are the most efficient syntheses of these materials to date. Factors influencing the stereochemical outcome of the reductive amination reaction were also explored, and evidence suggests that the reduction occurs from the least sterically hindered face of an intermediate cyclic imine, whereby the preferred conformation of the imine is the one which places the largest number of substituents in the pseudo-equatorial position. Using analogous methodology, the azepane (3S,4R,5S,6R)-azepane-3,4,5,6-tetraol was also prepared in 4 steps and good yield (53%).</p>

ChemInform Abstract: Protecting-Group-Free Synthesis of Amines: Synthesis of Primary Amines from Aldehydes via Reductive Amination.

ChemInform ◽  
2010 ◽  
Vol 41 (50) ◽  
pp. no-no
Author(s):  
Emma M. Dangerfield ◽  
Catherine H. Plunkett ◽  
Anna L. Win-Mason ◽  
Bridget L. Stocker ◽  
Mattie S. M. Timmer
Keyword(s):  
Reductive Amination ◽  
Primary Amines ◽  
Protecting Group

scholarly journals Methodology development for the synthesis of iminosugars

2021 ◽  
Author(s):  
◽  
Alexander Hunt-Painter
Keyword(s):  
Reductive Amination ◽  
Steric Effects ◽  
Primary Amines ◽  
Equatorial Position ◽  
Protecting Group ◽  
Efficient Synthesis ◽  
Electronic Effects ◽  
Synthetic Methodology ◽  
Methodology Development ◽  
The One

<p>This thesis investigated the development and application of methodology for the synthesis of iminosugars. The first portion of this thesis (Chapters 2 and 3) explored the scope of previously established protecting-group-free Vasella-reductive-amination and I2-mediated carbamate annulation methodology initially developed within the Stocker-Timmer group for the synthesis of pyrrolidines and piperidines from aldose sugars. In this thesis, the Vasella-reductive-amination methodology was extended to include the use of ketose sugars as starting materials, thereby allowing for the synthesis of primary amines directly from in situ formed ketones under protecting-group-free conditions. The scope of the carbamate annulation was then explored, whereby it was determined that both steric and electronic effects appear to affect transition state energies during the annulation reaction. Here, formation of pyrrolidines with the 2,5-trans and 3,4-cis relationships are favoured, however, in circumstances were conflicting electronic- and steric-effects are present, steric-effects dominate thereby favouring the formation of the 2,5-trans product. Using a combination of this Vasella-reductive-amination and carbamate annulation methodology, 2,5-dideoxy-2,5-imino-L-iditol was thus synthesised in 6 steps and 18% overall yield from D-fructose. Next, the same methodology was applied to the synthesis of the promising molecular chaperone 2,5-dideoxy-2,5-imino-D-altritol. Thus, 2,5-dideoxy-2,5-imino-D-altritol was synthesised over 7 steps and in 22% yield from D-tagatose, which is the most efficient synthesis of this iminosugar to date.  The second part of this thesis (Chapters 4 and 5) focused on the optimisation and development of synthetic methodology that would allow for the highly efficient synthesis of a variety of iminosugars including piperidines and azepanes. To this end, modifications to existing synthetic methodology allowed for the rapid synthesis of a variety of iodoglycosides, which are important synthons. Next, reductive amination/cyclisation methodology that allowed for the direct transformation of methyl iodoglycosides or isopropylidene-protected iodoglycosides into iminosugars was developed. As such, the piperidines 1-Deoxynojirimycin, 1-Deoxymannojirimycin (DMJ), L-1-Deoxygalactojirimycin (L-DGJ), and (3R,4r,5S)-piperidine-3,4,5-triol were prepared in 4 steps and good overall yields (44%, 62%, 67%, and 53%, respectively). In the case of DMJ and (3R,4r,5S)-piperidine-3,4,5-triol, these are the most efficient syntheses of these materials to date. Factors influencing the stereochemical outcome of the reductive amination reaction were also explored, and evidence suggests that the reduction occurs from the least sterically hindered face of an intermediate cyclic imine, whereby the preferred conformation of the imine is the one which places the largest number of substituents in the pseudo-equatorial position. Using analogous methodology, the azepane (3S,4R,5S,6R)-azepane-3,4,5,6-tetraol was also prepared in 4 steps and good yield (53%).</p>

Primary Amines by Transfer Hydrogenative Reductive Amination of Ketones by Using Cyclometalated IrIIICatalysts

2013 ◽  
Vol 20 (1) ◽  
pp. 245-252 ◽  
Author(s):  
Dinesh Talwar ◽  
Noemí Poyatos Salguero ◽  
Craig M. Robertson ◽  
Jianliang Xiao
Keyword(s):  
Reductive Amination ◽  
Primary Amines

Ambient-Temperature Synthesis of Primary Amines via Reductive Amination of Carbonyl Compounds

ACS Catalysis ◽  
2020 ◽  
Vol 10 (14) ◽  
pp. 7763-7772 ◽  
Author(s):  
Chao Xie ◽  
Jinliang Song ◽  
Manli Hua ◽  
Yue Hu ◽  
Xin Huang ◽  
...  
Keyword(s):  
Ambient Temperature ◽  
Carbonyl Compounds ◽  
Reductive Amination ◽  
Primary Amines ◽  
Temperature Synthesis

ChemInform Abstract: The “Benzostabase” Protecting Group for Primary Amines. Application to Aliphatic Amines.

ChemInform ◽  
2010 ◽  
Vol 23 (15) ◽  
pp. no-no
Author(s):  
R. P. BONAR-LAW ◽  
A. P. DAVIS ◽  
B. J. DORGAN ◽  
M. T. REETZ ◽  
A. WEHRSIG
Keyword(s):  
Aliphatic Amines ◽  
Primary Amines ◽  
Protecting Group

Selective Synthesis of Primary Amines by Reductive Amination of Ketones with Ammonia over Supported Pt catalysts

ChemCatChem ◽  
2015 ◽  
Vol 7 (6) ◽  
pp. 921-924 ◽  
Author(s):  
Yoichi Nakamura ◽  
Kenichi Kon ◽  
Abeda Sultana Touchy ◽  
Ken-ichi Shimizu ◽  
Wataru Ueda
Keyword(s):  
Reductive Amination ◽  
Primary Amines ◽  
Selective Synthesis ◽  
Pt Catalysts ◽  
Supported Pt Catalysts

scholarly journals Homogeneous cobalt-catalyzed reductive amination for synthesis of functionalized primary amines

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kathiravan Murugesan ◽  
Zhihong Wei ◽  
Vishwas G. Chandrashekhar ◽  
Helfried Neumann ◽  
Anke Spannenberg ◽  
...  
Keyword(s):  
Density Functional ◽  
Reductive Amination ◽  
Primary Amines ◽  
Metal Catalyst ◽  
Gaseous Ammonia ◽  
Free Energy Surface ◽  
Chemical Research ◽  
Rate Determining Step ◽  
Earth Abundant ◽  
Density Functional Theory Computation

AbstractThe development of earth abundant 3d metal-based catalysts continues to be an important goal of chemical research. In particular, the design of base metal complexes for reductive amination to produce primary amines remains as challenging. Here, we report the combination of cobalt and linear-triphos (bis(2-diphenylphosphinoethyl)phenylphosphine) as the molecularly-defined non-noble metal catalyst for the synthesis of linear and branched benzylic, heterocyclic and aliphatic primary amines from carbonyl compounds, gaseous ammonia and hydrogen in good to excellent yields. Noteworthy, this cobalt catalyst exhibits high selectivity and as a result the -NH2 moiety is introduced in functionalized and structurally diverse molecules. An inner-sphere mechanism on the basis of the mono-cationic [triphos-CoH]+ complex as active catalyst is proposed and supported with density functional theory computation on the doublet state potential free energy surface and H2 metathesis is found as the rate-determining step.

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