Polymer-Bound 3-N,N-(Dimethylamino)-2-isocyanoacrylate for the Synthesis of Thiazoles via a Multicomponent Reaction

Abstract

S y n t h e s i s o f P o l y m e r -B o u n d 3 -N , N -( D i m e t h y l a m i n o ) -2 -i s o c y a n o a c r y l a t e Abstract: The synthesis of resin-bound 3-N,N-(dimethylamino)-2-isocyanoacrylate is described. This bifunctional reagent can be used for the synthesis of thiazoles via a multicomponent reaction. Several examples are reported.

Isocyanide Multicomponent Reactions on Solid Phase: State of the Art and Future Application

“…Polymer-supported carbonate convertible isocyanide 58 could be used to prepare a 4000-membered library. The last polymer-supported convertible isocyanide discussed in this review is 3-N,N-(dimethylamino)-2-isocyanoacrylate resin 59 (Scheme 13) [52], which was applied for the synthesis of thiazoles (cf. Scheme 68).…”

“…In a follow-up synthesis, Dömling et al applied 3-N,N-(dimethylamino)-2-isocyanoacrylate attached to resin 59 (for its preparation, cf. Scheme 13) to synthesize thiazoles 408 (Scheme 68) [52]. Thiobenzoic acid afforded slightly higher yields than thioacetic acid.…”

“…Alternatively, glyoxal was used as the aldehyde component in U-4CR, and the second carbonyl functionality was employed for the imidazole ring formation [50]. Alcohol was used as an acid component [39], or application of thiocarboxylic [51,52], cyanic [53,54], thiocyanic, or hydrazoic acid [54] was reported in the literature. Alternatively, one starting component can bear two functional groups, e.g., ketoacid, thus serving as both ketone and carboxylic acid [1,54].…”

1-Isocyano-2-dimethylamino-alkenes: Versatile Reagents in Diversity-Oriented Organic Synthesis

“…27 As compared to other described methods by multi-step chemistries on the resin, the isocyanide is assembled separately in solution and is finally at- tached to the resin. These isocyanoacetic acid resins can than be converted to 1a and 1b and are useful for the solid phase synthesis of substituted thiazoles 28 and other heterocycles (Scheme 6). 29 Scheme 6 Synthesis of resin-bound variations of 1.…”

2,4,5-Trisubstituted Thiazole Building Blocks by a Novel Multi-Component Reaction

“…ceutical potential of these thiazole-containing natural products led to the development of several multi-step synthetic protocols for their total synthesis [16][17][18] and to different combinatorial modifications. [19][20][21][22][23][24][25][26] Dömling et al developed the first true multicomponent single step reaction towards 2,4-disubstituted thiazoles using b-dimethylamino-isocyanoacrylates. 27 This isocyanide was first described by Schöllkopf et al It contains a dimethylamino leaving group in the b-position suitable for one-pot, four-component thiazole synthesis.…”