Combinatorial Synthesis of C(2), C(3)-Disubstituted 3-Hydroxypropionamides Utilizing Baylis-Hillman Reactions on Solid Support

Solid-Phase Synthesis of β-Keto Esters via Sequential Baylis−Hillman and Heck Reactions

“…Initially, we examined Michael addition of amines as a route to functionalization of the adduct and identified the β-amino acid product (Scheme ) after resin cleavage by trifluoroacetic acid (TFA). Meanwhile, similar Michael additions to Baylis−Hillman products on solid phase were reported . We then investigated further reactions of the Michael adduct involving cyclization to β-lactams or azetidines.…”

Recent developments in solid-phase organic synthesis

“…By judicious choice of palladium catalyst, either primary or secondary amines could be coupled to the readily accessible aryl bromides 127 with minimal formation of reduction by-products (Scheme 55). 131 Carbon-nitrogen bonds are readily formed by nucleophilic addition and substitution reactions of electron deficient unsaturated compounds, 34,120,132 examples can be found in other sections of this review (see Schemes 6,19,46,77 and 81).…”

“…A Baylis-Hillman reaction, conducted with an α,βunsaturated ester component 12 attached to the solid support, was used to synthesise 3-hydroxypropionamides 15 (Scheme 6). 34 The ester linker was cleaved using primary amines in the presence of Me 3 Al.…”

Solid Phase Synthesis

“…Künzer et al 44 of Schering AG reported the optimisation of the Baylis Hillman reaction of a set of aldehydes to polymer-bound acrylic acid followed by the Michael additions of secondary amines (see Scheme 18).…”