163061-73-2Relevant academic research and scientific papers
Highly efficient enantioselective liquid-liquid extraction of 1,2-amino-alcohols using SPINOL based phosphoric acid hosts
Pinxterhuis, Erik B.,Gualtierotti, Jean-Baptiste,Heeres, Hero J.,De Vries, Johannes G.,Feringa, Ben L.
, p. 6409 - 6418 (2017)
Access to enantiopure compounds on large scale in an environmentally friendly and cost-efficient manner remains one of the greatest challenges in chemistry. Resolution of racemates using enantioselective liquid-liquid extraction has great potential to meet that challenge. However, a relatively feeble understanding of the chemical principles and physical properties behind this technique has hampered the development of hosts possessing sufficient resolving power for their application to large scale processes. Herein we present, employing the previously untested SPINOL based phosphoric acids host family, an in depths study of the parameters affecting the efficiency of the resolution of amino-alcohols in the optic of further understanding the core principles behind ELLE. We have systematically investigated the dependencies of the enantioselection by parameters such as the choice of solvent, the temperature, as well as the pH and bring to light many previously unsuspected and highly intriguing interactions. Furthermore, utilizing these new insights to our advantage, we developed novel, highly efficient, extraction and resolving protocols which provide remarkable levels of enantioselectivity. It was shown that the extraction is catalytic in host by demonstrating transport in a U-tube and finally it was demonstrated how the solvent dependency could be exploited in an unprecedented triphasic resolution system.
Highly Efficient and Robust Enantioselective Liquid–Liquid Extraction of 1,2-Amino Alcohols utilizing VAPOL- and VANOL-based Phosphoric Acid Hosts
Pinxterhuis, Erik B.,Gualtierotti, Jean-Baptiste,Wezenberg, Sander J.,de Vries, Johannes G.,Feringa, Ben L.
, p. 178 - 184 (2017/12/15)
The large-scale production of enantiopure compounds in a cost-effective and environmentally friendly manner remains one of the major challenges of modern-day chemistry. The resolution of racemates through enantioselective liquid–liquid extraction was developed as a suitable solution but has remained largely underused, owing to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a poor understanding of the underlying principles behind these processes hindering the design of more efficient selectors. A previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, has been studied in depth for the efficient enantioselective liquid–liquid extraction of 1,2-amino alcohols. A systematic investigation of extraction parameters was conducted, revealing many key interactions and DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now-optimized, procedures are highly robust and easy to implement. They are also easily scalable, as demonstrated by U-tube experiments.
3,3′-diaryl-BINOL phosphoric acids as enantioselective extractants of benzylic primary amines
Verkuijl, Bastiaan J.V.,De Vries, Johannes G.,Feringa, Ben L.
experimental part, p. 34 - 43 (2011/10/08)
We report that 3,3′-diaryl-BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid-liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3′-positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV-Vis, and CD spectroscopy, which provided insight into the structure of the host-guest complex involved in extraction.
COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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Page/Page column 45-49; 53, (2010/12/31)
The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
Development of new HPLC chiral stationary phases based on native and derivatized cyclofructans
Sun, Ping,Wang, Chunlei,Breitbach, Zachary S.,Zhang, Ying,Armstrong, Daniel W.
experimental part, p. 10215 - 10226 (2010/05/01)
An unusual class of chiral selectors, cyclofructans, is introduced for the first time as bonded chiral stationary phases. Compared to native cyclofructans (CFs), which have rather limited capabilities as chiral selectors, aliphatic-and aromatic-functionalized CF6s possess unique and very different enantiomeric selectivities. Indeed, they are shown to separate a very broad range of racemic compounds. In particular, aliphatic-derivatized CF6s with a low substitution degree baseline separate all tested chiral primary amines. It appears that partial derivatization on the CF6 molecule disrupts the molecular internal hydrogen bonding, thereby making the core of the molecule more accessible. In contrast, highly aromaticfunctionalized CF6 stationary phases lose most of the enantioselective capabilities toward primary amines, however they gain broad selectivity for most other types of analytes. This class of stationary phases also demonstrates high "loadability" and therefore has great potential for preparative separations. The variations in enantiomeric selectivity often can be correlated with distinct structural features of the selector. The separations occur predominantly in the presence of organic solvents.
Convenient and inexpensive synthesis of (1R,2R)-trans-1-amino-6-nitroindan- 2-ol
Kozhushkov, Sergei I.,Yufit, Dmitrii S.,De Meijere, Armin
, p. 255 - 265 (2007/10/03)
Racemic trans-1-amino-6-nitroindam-2-ol (rac-1) has been prepared in five steps from inexpensive indene (7) in 96% overall yield. The key step was a direct nitration of the known trans-1-aminoindan-2-ol (rac-9) which gave sulfuric acid mono-(rac-trans-1-amino-6-nitroindan-2-yl) ester (rac-10) in quantitative yield. The latter was quantitatively converted into rac-1 by treatment with aqueous 6 N HCl and then ammonia solutions. The same transformations of (1R,2R)-9 [prepared by deracemization of rac-9 with (-)-dibenzoyl-L-tartaric acid (DBT)] proceeded without loss of the optical activity. Deracemization of rac-1 applying (+)-(5)-L-mandelic acid (MA) furnished (1R,2R)-1 and (1s,2s)-1 in 34 and 17% yield, respectively, with e.e. ≥ 98 and 97.6%, respectively. Procedures for recycling of the chiral auxiliaries DBT and MA are also described. The structures of key intermediates were confirmed by X-ray crystal structure analysis.
Asymmetric transfer hydrogenation of ketones using amino alcohol and monotosylated diamine derivatives of indane
Palmer, Matthew J.,Kenny, Jennifer A.,Walsgrove, Tim,Kawamoto, Aparecida M.,Wills, Martin
, p. 416 - 427 (2007/10/03)
A series of 1,2-amino alcohol and 1,2-monotosylated diamine derivatives of indane have been applied as ligands in the asymmetric ruthenium(II)-catalysed transfer hydrogenation reaction of a series of ketones. Of these, the cis-1-aminoindan-2-ol derivative gives some of the highest asymmetric inductions reported for any amino alcohol ligand in this application.
A practical synthesis of (1S,2R)-1-amino-2-indanol, a key component of an HIV protease inhibitor, indinavir
Kajiro, Hiroshi,Mitamura, Shuichi,Mori, Atsunori,Hiyama, Tamejiro
, p. 1093 - 1100 (2007/10/03)
A synthesis of (1S,2R)-1-amino-2-indanol (1), a key component of an HIV protease inhibitor, was accomplished through (R)-2-hydroxy-1-indanone ((R)- 3), which was prepared by an intramolecular Friedel-Crafts acylation of (R)2- acetoxy-3-phenylpropanoic acid readily available from D-(R)-phenylalanine. Alternatively, (R)-3 was obtained by an enzymatic resolution of (±)-2- acetoxy-1-indanone. Ketone (R)-3 was convened into 1 through an oxime formation and diastereoselective hydrogenation.
