Accelerated Growth of Dendrimers via Thiol−Ene and Esterification Reactions

Abstract

By taking advantage of the orthogonal nature of thiol-ene coupling and anhydride based esterification reactions, a facile and chemoselective strategy to dendritic macromolecules has been developed. The ability to interchange growth steps based on thiol-ene and anhydride chemistry allows the synthesis of fifth-generation dendrimers in only five steps and under benign reaction conditions. In addition, the presented coupling chemistries eliminate the traditional need for protection/deprotection steps and afford dendrimers in high yield and purity. The modularity of this strategy coupled with the latent reactivity of the alkene/hydroxyl chain ends was demonstrated by using different cores (alkene and hydroxyl functional), various AB 2 and CD 2 monomers and a range of chain end groups. As a result, three dendritic libraries were prepared which exhibited tunability of both the chemical functionality and physical properties including the fabrication of PEG hydrogels.

Polyester Dendrimers

“…The first example of this strategy incorporating ester units, shown in Schemes 4 and 5, used the Mitsunobu reaction to form esters [102] and Sonagashira coupling as its orthogonal partner [102]. More recent examples of orthogonal coupling in which ester formation is one of the two coupling reactions include the following: ester formation and click reactions [103], ester formation and thiol-ene reactions [104,105], thiol displacement of α-ketohalides and ester formation [95], ester and amide formation [106], and thiol-yne reaction and ester formation [107] (see Section 4.4).…”

“…A variant of this approach can yield dendrimers with a greater number of functional groups on the periphery with fewer synthetic steps if the two orthogonal reactions both employ branched dendrons [93,98,103,104,[108][109][110] Scheme 5. Formation of an alternating polyester dendrimer [102].…”

“…The starting materials and second generation dendron for accelerated synthesis [103]. Montañez utilized AB 2 dendrons that combined ester formation with thiol-ene reactions to provide another approach for the accelerated synthesis of dendrimers [104]. These authors combined the dendrons shown in Figure 11 as shown in Scheme 74.…”

“…Figure 11. Monomers and cores employed for the synthesis of dendrimers using thiol-ene and esterification reactions [104].…”

Recent advances on crosslinked dendritic networks

“…With the introduction of robust organic concepts, namely click reactions, rapid and facile synthesis of dendrimers has been realized by so‐called accelerated growth approaches . By utilizing orthogonal coupling reactions, the activation steps become obsolete, making the synthesis route more effective and reducing the number of reaction steps by 50% …”