The Usefulness of Trivalent Phosphorus for the Synthesis of Dendrimers

Abstract

Dendrimers are hyperbranched macromolecules, which are synthesized step-by-step by the repetition of a series of reactions. While many different types of dendrimers are known, this review focusses on the use of trivalent phosphorus derivatives (essentially phosphines and phosphoramidites) for the synthesis of dendrimers. The first part presents dendrimers constituted of phosphines at each branching point. The other parts display the use of trivalent phosphorus derivatives during the synthesis of dendrimers. Different types of reactions have been applied to phosphines. The very first examples of phosphorus-containing dendrimers were obtained by the alkylation of phosphines. Then, several families of dendrimers were elaborated by reaction of phosphoramidites. Such a type of reaction is the base of the solid phase synthesis of oligonucleotides; it has been applied in particular for the synthesis of dendrimers constituted of oligonucleotides. Finally, the Staudinger reaction between phosphines and azides afforded different families of dendrimers, and was at the origin of accelerated methods of synthesis of dendrimers. Besides, the reactivity of the P=N-P=S linkages created by this reaction led to very original dendritic structures.

Keywords: Staudinger reaction; alkylation; dendrimers; phosphines; phosphoramidites.

Figure 1

Two types of schematized structure of dendrimers (generation 4) having phosphorus atoms at each branching point, either of type phosphine, or issued from the reaction of phosphines. (A): Full structure; (B): Linear representation of the same dendrimer.

Scheme 1

The first example of dendrimers constituted of phosphines at each branching point.

Scheme 2

Synthesis of a large phosphine dendrimer, and its complexation with rhodium.

Figure 2

Full chemical structure of the dendritic complex 2-G4-Rh, synthesized as shown in Scheme 2.

Scheme 3

Small acetylenic phosphine dendrimers.

Scheme 4

Synthesis of boranophosphate triesters and phosphite-based dendrimers.

Scheme 5

Oxidation with sulfur and complexation with rhodium of a 2nd generation phosphite dendrimer.

Scheme 6

Alkylation of phosphines for the synthesis of phosphonium dendrimers up to the third generation.

Scheme 7

Phosphonium dendrimers having a phosphine oxide, a phosphine, or a phosphine complexing gold at the core.

Figure 3

Phosphonium dendrimer built from a quinque-directional phosphorane core.

Scheme 8

Synthesis via a convergent process of nucleic acid dendrimers based on thymidine (T) for the branches and adenosine (A) 2′,3′-bis(phosphoramidite) reagent for the branching points.

Scheme 9

Structure of phosphoramidite reagents used for chain extension (I) and branching (II), and the divergent synthesis of nucleic acid dendrimers 9-G2, in the solid phase.

Figure 4

Phosphoramidite functionalized with pentaerythritol structure for branching and phosphoramidite functionalized with an oligoethyleneoxide chain to reduce the density of packing. Structure of dendrons bearing an oligonucleotide at the core and pentathymidine on the surface.

Scheme 10

Synthesis of thiophosphate dendrimers, using a phosphoramidite as phosphitylating agent.

Scheme 11

Synthesis of selenophosphate dendrimers and oxygenation to phosphate dendrimers.

Figure 5

Layered dendrimers bearing three different types of branching units (P=Se, P=S, P=O).

Figure 6

The various building blocks based on phosphoramidite reagents used for the synthesis of dendrimers built with perylenes in the branches, and schematization of the type of dendrimers obtained.

Scheme 12

The first example of dendrimers synthesized using the Staudinger reaction between phosphines and azides at one of the three steps needed to build one generation.

Figure 7

Full chemical structure of the dendrimer 12a-G3, the linear form of which is shown in Scheme 12.

Scheme 13

Synthesis of small dendrimers using the Staudinger process.

Scheme 14

Synthesis of dendrimers using a single monomer at each step, for each generation.

Figure 8

Full chemical structure of the dendrimer 14-G5 shown in a linear form in Scheme 14.

Figure 9

Another dendrimer synthesized as shown in Scheme 14, starting from triphenyl phosphine as the core.

Scheme 15

Synthesis of layered dendrimers using two branched monomers of types AB₂ and CD₂. Only one step is needed for the synthesis of one generation.

Figure 10

Full chemical structure of the layered dendrimer 15-G4, for which the linear structure is shown in Scheme 15.

Scheme 16

Synthesis of layered dendrimers based on the reaction with the CA₂ and DB₂ branched monomers.

Scheme 17

Synthesis of layered dendrimers based on the reactions with the AB₅ and CD₂ branched monomers.

Scheme 18

Synthesis of layered dendrimers based on the reactions with the AB₂ and CD₅ branched monomers.

Figure 11

Comparison between the full structure of the second-generation dendrimers 17-G2 and 18-G2.

Scheme 19

Synthesis of the third generation dendrimer 19-G3 in only 3 steps, functionalized with 750 phosphine terminal functions.

Figure 12

Full chemical structure of dendrimer 19-G2, functionalized with 150 aldehyde terminal functions, built with AB₅ and CD₅ monomers, for which the linear structure is shown in Scheme 19.

Scheme 20

Alkylation on sulfur of P=N-P=S linkages of a first-generation dendrimer, and schematization of the same reaction on a generation 7 dendrimer, having 2 P=N-P=S linkages at the core, 64 at the level of the fifth generation, and 256 at the seventh generation. The structure of 20-G6 showing the place of two layers of P=N-P=S linkages.

Scheme 21

Different types of reactions carried out on the P=N-P=S linkages in the internal structure of dendrimer 21-G3.

Figure 13

Full structure of the dendrimer 21-G3-CE bearing 12 crown ether derivatives inside its structure.

Scheme 22

Synthesis of branches inside a dendrimer, up to 22-G3@21-G3.

Figure 14

Full structure of dendrimer 22-G3@21-G3. The newly synthesized branches are represented in blue.

Scheme 23

A three-step method for growing new branches inside a dendrimer, up to 23-G3@21-G3.

Scheme 24

Grafting of 12 dendrons inside the structure of a dendrimer, up to 24-G3@21-G3.

Scheme 25

Selective complexation of gold by P=N-P=S and P=N-P=N-P=S linkages.

Scheme 26

Complexation of gold by the small 26-G0 dendrimer and TEM images of gold nanoparticles generated only by addition of water to the dendrimer complex (images from Ref. [52], copyright Caminade et al., open access article).