Boronate linkers

Boronic acid hnkers (Tab. 3.6) are useful for the attachment of diols, the protection of glycosides [105] or as precursors for the metal-mediated cleavage [106]. The boronates formed are sensitive to water and simple hydrolysis is sufficient for cleavage. Recently, Carreaux and Carboni developed a new boronate-based strategy for traceless sohd-phase synthesis of aromatic compounds [107]. 

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Pourbaix C, Carreaux F, Carboni B, Deleuze H, Boronate linker for traceless solid-phase synthesis, Chem. Commun., 14 1275-1276, 2000. 

Scheme 20.18 Regio-orientation strategy using boronate linkers attached to PS.

Fig. 2. Concept of molecular imprinting - the covalent approach. 1. Derivatization of sugar template with p-vinylphenyl boronate. 2. Polymerization in the presence of a cross-linker...

The use of a p-vinylphenyl boronate as functional monomer to be covalently linked with a diol-template [2] is demonstrated in Fig. 2. Following polymerization in the presence of a cross-linker, the template has to be extracted from the polymer network. This requires breaking the covalent bond. During the application of covalently imprinted materials, the target molecules have to reform such bonds in order to be retained. Both making and breaking the bonds is at best a time-consuming process. 

Oxindoles are prepared using a solid-phase Pummerer reaction. Thus, the immobilized amide 182 undergoes the Pummerer rearrangement on treatment with TFAA and boron trifluoride diethyl etherate (BF3 Et20) (Equation 118). Cleavage of the oxindole from the linker is achieved using samarium iodide and 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU) <2003CC2380>. 

The work by Armstrong was extended to include the room temperature resin capture of trisubstituted ethenes with a pendant boronate group.80 Modification of the amide linker above to a novel silyl-based one allowed for the traceless cleavage of superior analogues. 

In a parallel study, Wipf and Fritch11041 have shown that also urethane-protected (Boc), and even amino acid segments, are tolerated as acyl compounds on the aziridine nitrogen. The best results were obtained with alkylcopper reagents derived from CuCN and an alkyl-lithium in the presence of boron trifluoride-diethyl ether complex. Some 6-alkylated compounds (11-15%) were isolated as well. This work was extended to a solid-phase procedure that resulted in resin-bound alkene isosteres that could immediately be used in further peptide synthesis.11051 For this purpose, the 2-nitrophenylsulfonyl (oNbs) group was used for nitrogen protection and aziridine activation. It could be readily cleaved with benzenethio-late, which was compatible with the acid-sensitive Wang linker used. 

Linkers for Thiocarboxylic, Boronic, Phosphonic, Phosphoric, and Sulfonic Acids... 

Polystyrene-derived phenylboronic acids have been used for the attachment of diols (carbohydrates) as boronic esters [667]. Cleavage was effected by treatment with acetone/water or THF/water. This high lability towards water and alcohols severely limits the range of reactions that can be performed without premature cleavage of this linker. Arylboronic acids esterified with resin-bound diols can be oxidatively cleaved to yield phenols (Entry 8, Table 3.36). Alcohols have also been prepared by nucleophilic allylation of aldehydes with polystyrene-bound, enantiomerically enriched allyl-silanes [668], as well as by Pummerer reaction followed by reduction of resin-bound sulfoxides [669]. 

As illustrated in the previous section, a broad variety of ambiphilic compounds have been prepared by varying the different components of the PB framework (linker, substituents at phosphorus and boron). 

The structure of 70 was established by X-ray diffraction analysis (Figure 22). The palladium center is only coordinated by the phosphorus atom of 32 (the sulfur atom remains pendant) and the dvds coligand (r 2 r 2 fashion), resulting in a slightly distorted trigonal planar geometry around the metal. The rigid thioxanthene linker maintains the boron atom remote from the coordination sphere of the metal. 

The sole coordination of the phosphine sites has also been observed with PBs featuring the flexible (CH2)2 linker. The coordination of ligands 40e and 40f to the [Ru(p-cymene)Cl2] fragment affords complexes 74a and 74b (Scheme 44). Despite the modest steric hindrance around boron, neither Cl-B (coordination mode F) nor Ru-B (coordination mode FI) interaction was found. Coordination mode E was established spectroscopically (8nB = 82 and 87 ppm for 74a and 74b, respectively) and confirmed crystallographically.55... 

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