Squaramide catalysis

{{Short description|Use of squaramides as hydrogen-bond catalyst to accelerate reactions}}

Within the area of organocatalysis, '''squaramide''' '''catalysis''' describes the use of squaramides to accelerate and stereochemically alter organic transformations. The effects arise through hydrogen-bonding interactions between the substrate and the squaramide, unlike classic catalysts, and is thus a type of hydrogen-bond catalyst. The scope of these small-molecule H-bond donors termed squaramide organocatalysis covers both non-stereoselective and stereoselective applications.<ref name=":0">{{Cite journal |last1=Popova |first1=E. A. |last2=Pronina |first2=Yu. A. |last3=Davtian |first3=A. V. |last4=Nepochatyi |first4=G. D. |last5=Petrov |first5=M. L. |last6=Boitsov |first6=V. M. |last7=Stepakov |first7=A. V. |date=2022-03-01 |title=Squaramide-Based Catalysts in Organic Synthesis (A Review) |url=https://doi.org/10.1134/S107036322203001X |journal=Russian Journal of General Chemistry |language=en |volume=92 |issue=3 |pages=287–347 |doi=10.1134/S107036322203001X |issn=1608-3350|url-access=subscription }}</ref>

==Structure== thumb|General structure of squaramide organocatalystA squaramide organocatalyst typically contains the squaramide group and a hydrogen bond donor which is usually a tertiary amine group. The 3,5-bis(trifluoromethyl)phenyl-group is commonly used for the R group. For enantioselective squaramide catalysis, chirality is induced via the tertiary amine group. There are cases where both sides of the squaramide are tertiary amines.<ref name=":0" />

== Catalyst-substrate interactions == thumb|Interaction between squaramide catalyst and substrate exemplified by the conjugate addition of an enolate to an unsaturated ketoneThe interaction between the substrate and the catalyst can be seen in the image above, with the electrophile being bound to the squaramide part and the protonated nucleophile to the amine part (which increases nucleophilicity). However, the position of the nucleophile and electrophile switch when the electrophile can only form one hydrogen bond, as in the case of most imines.<ref name=":0" />

== Advantages of squaramide organocatalysts == Squaramide catalysts are easily prepared from starting materials like methyl squarate, possess high activities under low catalyst loadings. Squaramide catalysis can be a replacement for thiourea organocatalysis in some scenarios.<ref name=":1">{{Cite journal |last1=Chauhan |first1=Pankaj |last2=Mahajan |first2=Suruchi |last3=Kaya |first3=Uğur |last4=Hack |first4=Daniel |last5=Enders |first5=Dieter |date=2015-02-09 |title=Bifunctional Amine-Squaramides: Powerful Hydrogen-Bonding Organocatalysts for Asymmetric Domino/Cascade Reactions |url=https://onlinelibrary.wiley.com/doi/10.1002/adsc.201401003 |journal=Advanced Synthesis & Catalysis |language=en |volume=357 |issue=2–3 |pages=253–281 |doi=10.1002/adsc.201401003 |issn=1615-4150|url-access=subscription }}</ref><ref name=":2">{{Cite journal |last1=Malerich |first1=Jeremiah P. |last2=Hagihara |first2=Koji |last3=Rawal |first3=Viresh H. |date=2008-11-05 |title=Chiral Squaramide Derivatives are Excellent Hydrogen Bond Donor Catalysts |journal=Journal of the American Chemical Society |language=en |volume=130 |issue=44 |pages=14416–14417 |doi=10.1021/ja805693p |issn=0002-7863 |pmc=2701638 |pmid=18847268|bibcode=2008JAChS.13014416M }}</ref> Squaramides have higher affinity for halide ions than thiourea.<ref>{{Cite journal |last1=Busschaert |first1=Nathalie |last2=Kirby |first2=Isabelle L. |last3=Young |first3=Sarah |last4=Coles |first4=Simon J. |last5=Horton |first5=Peter N. |last6=Light |first6=Mark E. |last7=Gale |first7=Philip A. |date=2012-04-27 |title=Squaramides as Potent Transmembrane Anion Transporters |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.201200729 |journal=Angewandte Chemie International Edition |language=en |volume=51 |issue=18 |pages=4426–4430 |doi=10.1002/anie.201200729 |pmid=22461434 |issn=1433-7851|url-access=subscription }}</ref>Aqueous mediums can be used.<ref name=":0" />

== Scope == H-bond accepting substrates include carbonyl compounds imines, Michael acceptors, and epoxides. The nucleophile can be nitroalkanes, enolates, and even phenols (resulting in electrophilic aromatic substitution). Subsequent cascade reactions are possible.<ref name=":0" /><ref>{{Cite journal |last1=Zhao |first1=Bo-Liang |last2=Du |first2=Da-Ming |date=2016-12-22 |title=Squaramide-Catalyzed Enantioselective Cascade Approach to Bispirooxindoles with Multiple Stereocenters |url=https://onlinelibrary.wiley.com/doi/10.1002/adsc.201600782 |journal=Advanced Synthesis & Catalysis |language=en |volume=358 |issue=24 |pages=3992–3998 |doi=10.1002/adsc.201600782 |issn=1615-4150|url-access=subscription }}</ref><ref name=":1" />

==History== Squaramides have been synthesized in 1966.<ref name=":0" /> Squaramide catalysts are developed in 2008 by Jeremiah P. Malerich, Koji Hagihara, and Viresh H. Rawal.<ref name=":0" /><ref name=":2" />

==Catalysts== From the general structure of squaramide catalysts, a number of catalysts have been developed, most with the aim to enable chiral catalysis. {{Gallery |File:2008 Squaramide catalyst.svg|The first squaramide catalyst developed. It functions as a bifunctional catalyst.<ref name=":2" />Some later catalysts are based on such a structure by removing the methylene group on the left to make a 3,5-bis(trifluoromethyl)phenyl-group or adding a 6-methoxy group on the quinoline.<ref name=":0" />|File:Zlotin's squaramide catalyst.png|Zlotin's bifunctional squaramide catalyst.<ref name=":0" />|File: Ionic liquid squaramide catalyst.png|Ionic liquid squaramide catalyst for catalyzing epoxide opening reaction. It can be directly separated via decantation.<ref name=":0" />Note that it is achiral.|File:Polymer squaramide catalyst.png|Polymeric squaramide catalyst that is only soluble in strongly polar solvents like DMF and DMSO, and thus can be easily separated.<ref name=":0" />|title=}}

==References== {{Reflist}}

Category:Catalysis Category:Organic chemistry