Silyl-based linkers

Silyl-based linker 23, cleaved by either basic (TBAF) or neutral (CsF) fluoridolysis to release carboxylic acids, alcohols, or amines, was prepared by treatment of a Grignard reagent to an aldehyde resin [28], To demonstrate the utility of this handle, /)-bromobenzoic acid was... 

Cleavage of all the linkers described above provide a functional group (carboxylic acid, amide, amine, etc) at the anchoring position. Silyl-based handles 71,72, and 73 as well as germanium-based handle 74 insert a C-H bond at the anchoring position and are referred to as traceless (Fig. 15) [82-... 

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. 

Two silyl-based linkers are also worthy of mention. Both linkers are cleaved by [1-... 

Silyl-based linkers were investigated to effect a nonbasic fluoride-mediated cleavage of the oligonucleotide from the solid support. The siloxyl, 42 [112,113], or disiloxyl, 43 [114], backbones were grafted on CPG or polystyrene supports. Release of the oligonucleotide was achieved by use of 0.5 M tetrabutylammonium fluoride in THF or DMF. Such conditions render the use of this linker structure less compatible with conventional 2 -0-TBDMS RNA chemistry. 

Silyl-derived linker 36 was prepared in three steps from a silyl ether of serine and incorporated for Fmoc/tBu-based assembly of protected gly-copeptide blocks (Scheme 11) [42]. The a-carboxylic acid function of serine was protected as an allyl ester. Deprotection by a Pd(0) catalyst in the presence of dimedone liberated the carboxylic acid in order for subsequent... 

Nakamura K, Hanai N, Kanno M, Kobayashi A, Ohnishi Y, Ito Y, Nakahara Y. Design and synthesis of silyl ether-based linker for solid-phase synthesis of glycopeptides. Tetrahedron Lett 1999 40 515-518. 

Details of the Janda-Chen synthesis were as follows. A tetrahydropyran (THP) linker was attached to the NCPS support enabling attachment of alcohols via THP ether formation.13 The THP-NCPS resin 1 is derivatized with / -(+)-4-hydroxy-2-cyclopentanone 2, giving the THP ether-based resin 3, followed by coupling of the C13 20 fragment by enone-cuprate addition. The cuprate required was generated from the corresponding E-vinyl stannane 4. The resulting enolate was trapped as the silyl end ether... 

The most prominent anchors for traceless linkage of arenes are based on silyl linkers. Generation of a diverse benzodiazepine library [40] has clearly shown the advantages of this type of detachment because no additional functionality, which might bias the library, was preserved in the final molecules (Scheme 6.1.33). 

Newly developed silicon hnkers such as 79 (Scheme 37) have been synthesized in fewer steps as compared with the earlier reported traceless linkers based on silyl functionalization. They allow for an easy binding to the support before performing the combinatorial synthesis [93, 94],... 

The traceless anchors based on silicon just described are limited by the need to synthesize a preformed handle consisting of the first building block and the silicon linker. Moreover, traceless release from conventional aryldialkylsilanes is complicated by their low hydrolytic stability and loss of silicon from the resin in the cleavage process. The silyl chloride resin 8h can be used to anchor aryl rings by reaction with aryllithium reagents. The anchor is stable to concentrated TFA and bases, but treatment with TBAF cleaves the final products [353]. 

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