Linker boron linkers

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... 

Resin-based chemistry has been used to construct 480 from 481 by use of boron trifluoride to mediate both the cyclization and cleavage steps <1999AGE1121 >. When the monosaccharide was bound to the polystyrene resin (Merrifield and MPP type) by an alkylsulfonyl linker 482 and cyclization was mediated by 2- r/-butylimino-2-diethylamino-l,3-dimethylperhydro-l,3,2-diazaphosphorine, the reaction had low stereoselectivity and the products included tricyclic oxetanes and oxiranes <2004EJ04177>. The Mitsunobu reaction was used to obtain intramolecular N-alkylation of 483 and formation of 484 <2005AGE3732>. 

Boronates have been used in a variety of linker types either as linkers for diols [42] or as precursors for metal-mediated cleavage. A boronic acid ester, which contains an aryl iodide moiety attached by an appropriate tether, can act as an intramolecular arylation agent. A polymer-bound precursor furnished a macrocydic constrained / -tum peptide mimic via biaryl coupling, leading to cleavage [43] (Scheme 6.1.10). 

Barth et alJ30 have reported the preparation of boronated starburst dendrimer— monoclonal antibodies immunoconjugates as a potential delivery system for boron neutron capture therapy. 31 32 Starburst dendrimers have also been employed as linker molecules for the covalent connection of synthetic porphyrins to antibodies J33 ... 

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

The diethanolamine linker 1.13 (70), obtained from aminomethyl PS resin and ethylene oxide, has been used to support boronic acids which, after SP transformations, were released with THF/H2O/ACOH 18/1/1 in 1 h at rt or, when acid-labile boronic acids were involved, with THF/H2O 9/1 in 2 h at rt. 

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