20799-66-0Relevant academic research and scientific papers
Coupling Interrupted Fischer and Multicomponent Joullié-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics
Alfano, Antonella Ilenia,Buommino, Elisabetta,Ferraro, Maria Grazia,Irace, Carlo,Zampella, Angela,Lange, Heiko,Brindisi, Margherita
supporting information, p. 3795 - 3809 (2021/10/20)
The generation of peptidomimetic substructures for medicinal chemistry purposes requires effective and divergent synthetic methods. We present in this work an efficient flow process that allows quick modulation of reagents for Joullié-Ugi multicomponent reaction, using spiroindolenines as core motifs. This sterically hindered imine equivalent could successfully be diversified using various isocyanides and amino acids in generally good space-time yields. A telescoped flow process combining interrupted Fischer reaction for spiroindolenine synthesis and subsequent Joullié-Ugi-type modification resulted in product formation in very good overall yield in less than 2 hours compared to 48 hours required in batch mode. The developed protocol can be seen as a general tool for rapid and facile generation of peptidomimetic compounds. We also showcase preliminary biological assessments for the prepared compounds.
Trityl Isocyanide as a Mechanistic Probe in Multicomponent Chemistry: Walking the Line between Ugi- and Strecker-type Reactions
Cioc, Rǎzvan C.,Preschel, Hans D.,Van Der Heijden, Gydo,Ruijter, Eelco,Orru, Romano V. A.
supporting information, p. 7837 - 7842 (2016/06/09)
Herein, we describe the versatile application of triphenylmethyl (trityl) isocyanide in multicomponent chemistry. This reagent can be employed as a cyanide source in the Strecker reaction and as convertible isocyanide in the preparation of N-acyl amino acids by Ugi 4CR/detritylation and free imidazo[1,2-a]pyridin-3-amines by a Groebke-Blackburn-Bienaymé 3CR condensation/deprotection protocol. The mechanisms of these three classical MCRs intersect at the common N-trityl nitrilium ion intermediate, whose predictable reactivity can be exploited towards chemoselective transformations. Fate of the nitrilium ion: The application of trityl isocyanide as a mechanistic tool to dissect different reaction pathways in multicomponent chemistry is described. This reagent can be employed as a cyanide source in the Strecker reaction and as a convertible isocyanide in the preparation of N-acyl amino acids by Ugi 4CR/detritylation and free imidazo[1,2-a]pyridin-3-amines by Groebke-Blackburn-Bienaymé 3CR condensation/deprotection. Chemoselective transformations were achieved by the rational choice of reaction conditions.
Zinc chloride homogeneous catalysis in the tritylation of hydroxyl- and amide-bearing molecules
Maltese, Maurizio,Vergari, Maria Cecilia,Donzello, Maria Pia
supporting information; experimental part, p. 483 - 487 (2011/03/18)
A tritylation protocol based on the transfer of the triphenylmethylcarbenium ion from trityl acetate to substrates having hydroxyls, in the presence of catalytic amounts of ZnCl2, is described. The advantages of this method are broad scope, mild conditions, and easy handling. The comparison with the procedure based on the use of equimolar mixture of TrCl and ZnCl2 in the presence of TEA shows that comparable results are obtained. However, only this method allows reactions of secondary or benzylic alcohols such as oxidation or formation of symmetric ethers to be suppressed. Both procedures are successfully extended to simple and substituted amides. Irrespective of its low solubility in acetonitrile, even asparagine can be directly tritylated on its amide group.
A novel modification of the Ritter reaction using trimethylsilyl cyanide
Chen,Goel,Kesten,Knobelsdorf
, p. 8129 - 8132 (2007/10/03)
A new modification of the Ritter reaction using trimethylsilyl cyanide (Me3SiCN) is described, which converts alcohols to their corresponding formamides in high yields using a convenient procedure. The reaction conditions and mechanism are discussed. In some cases, new formamides are synthesized which cannot be prepared by the classical Ritter reaction.
