Trityl Isocyanide as a Mechanistic Probe in Multicomponent Chemistry: Walking the Line between Ugi- and Strecker-type Reactions.
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.
Department of Chemistry & Pharmaceutical Sciences and, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Răzvan C
RC
Cioc
Department of Chemistry & Pharmaceutical Sciences and, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Hans D
HD
Preschel
Department of Chemistry & Pharmaceutical Sciences and, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Gydo
G
van der Heijden
Department of Chemistry & Pharmaceutical Sciences and, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Eelco
0000-0002-1105-3947
E
Ruijter
Department of Chemistry & Pharmaceutical Sciences and, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands. r.v.a.orru@vu.nl.
Romano V A
RV
Orru
D000215:Acylation; D000586:Amination; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D003486:Cyanides / Q000138:chemical synthesis / Q000737:chemistry*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D014320:Triphenylmethyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D000596:Amino Acids; D003486:Cyanides; D007093:Imidazoles; D007202:Indicators and Reagents; D011725:Pyridines; D014320:Triphenylmethyl Compounds
chemoselectivity; isocyanides; multicomponent reactions; nitrilium ion; reactive intermediates