Polymer-supported Silyl Research Articles

Polymer compositions on kinetic resolution of secondary alcohols using polymer-supported silyl chlorides

Modulating the polarity of the polymer backbone affects the selectivity of asymmetric silylation.

Total synthesis of cyclodepsipeptide spiruchostatin A on silyl-linked polymer-support

Abstract Solid-phase total synthesis of cyclodepsipeptide spiruchostatin A (1) has been achieved. Initially, immobilization of the Boc- d -Val-statine derivative 3 via the hindered β-hydroxy group was efficiently achieved using polymer-supported silyl triflate. Subsequently, the peptide chain was successfully extended on the polymer-support to yield the tetrapeptide cyclization precursor 2 with high purity. 2-Methyl-6-nitrobenzoic anhydride (MNBA)-mediated macrolactonization of 2 proceeded smoothly on the polymer-support to provide macrolactone 12. Finally, release of the macrolactone from the polymer-support followed by in situ disulfide formation furnished spiruchostatin A (1) in 17% overall yield.

Polymer-supported silyl cyanide and silyl azide: Useful reagents for solid-phase applications

The support of a delicate reagent on a solid matrix allows for better and safer handling of the reagent itself. Because we had an interest in silicon-based supported reagents(1) we turned our attention to a polymer-supported trialkylsilyl cyanide and trialkylsilyl azide starting from a commercially available trialkylsilane resin. The supported cyanide was obtained with excellent yield and proved to be shelf-stable. This supported reagent was reacted with a series of aldehydes and ketones yielding the corresponding polymer-supported cyanohydrins in good-to-excellent yields. A stability study on a model cyanohydrin demonstrated that these supported intermediates also can be stored for a prolonged time. For the last step, a cleavage strategy that could release either cyanohydrins or alpha-hydroxy esters was adopted. Finally, we prepared a polymer-supported trialkylsilyl azide, which also proved to be shelf-stable.

Polymer-supported silyl cyanide and silyl azide: Useful reagents for solid-phase applications

The support of a delicate reagent on a solid matrix allows for better and safer handling of the reagent itself. Because we had an interest in silicon-based supported reagents1 we turned our attention to a polymer-supported trialkylsilyl cyanide and trialkylsilyl azide starting from a commercially available trialkylsilane resin. The supported cyanide was obtained with excellent yield and proved to be shelf-stable. This supported reagent was reacted with a series of aldehydes and ketones yielding the corresponding polymer-supported cyanohydrins in good-to-excellent yields. A stability study on a model cyanohydrin demonstrated that these supported intermediates also can be stored for a prolonged time. For the last step, a cleavage strategy that could release either cyanohydrins or α-hydroxy esters was adopted. Finally, we prepared a polymer-supported trialkylsilyl azide, which also proved to be shelf-stable. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng (Comb Chem) 71:38–43, 2000.

A polymer-supported silyl triflate and subsequent functionalization: synthesis and solid-phase Diels-Alder reactions of silyloxydienes

Abstract The synthesis of a polymer-supported silyl triflate and subsequent functionalization with enolizable α, β-unsaturated aldehydes and ketones to form silyloxydienes is reported herein. This novel route is ideal for the generation of substrates for solid-phase Diels-Alder reactions. The silyl triflate and diene synthesis, subsequent [4 + 2] cycloadditions, and electrophilic cleavage are described. Download full-size image

New methodologies for the synthesis of compound libraries

New methodologies for the synthesis of compound libraries are discussed. They are based on new carbon–carbon bond-forming reactions on the solid-phase (using polymer-supported silyl enol ethers), library preparation using polymer catalysts, and multi-component reactions in liquid phase. Development of new linker resins for efficient reactions on the solid-phase and a new method for the synthesis of monosaccharide libraries are also described.

Functional Polymers from (Vinyl)polystyrene. Recyclable Polymer-Supported Organosilicon Protecting Groups for Solid-Phase Synthesis

Dicobalt octacarbonyl catalyzed the hydrosilylation of residual vinyl groups on insoluble porous beads of divinylbenzene-rich copolymer, exclusively with β orientation, by either dialkylhalosilanes or alkyldihalosilanes. The resulting silyl halide functionalities, now bound to a cross-linked polystyrene matrix through stable dimethylene spacers, could then be used to protect and immobilize hydroxyl-containing free molecules for their further modification in the course of solid-phase synthesis. The reaction proved selective for primary hydroxyls in the presence of secondary, and secondary over tertiary. Together with product free alcohols, later cleavage of these silyl ethers with aqueous acid or base also released the corresponding silanol groups, while HF, under particularly mild and selective conditions, left silyl fluorides that themselves could then be very conveniently regenerated by BCl3/CH2Cl2 back to the polymer-supported silyl chlorides. For a variety of possible applications, these solid-phase p...

5-(4′-chloromethylphenyl)pentylpolystyrene resin (CMPP resin). A new linker resin for solid-phase organic synthesis under Lewis acidic conditions

A new linker resin for solid-phase organic synthesis under Lewis acidic conditions has been developed. The resin, 5-(4′-chloromethylphenyl)pentylpolystyrene resin (CMPP resin), has no oxygen or nitrogen atoms in its spacer moiety. Imino aldol reactions of polymer-supported silyl enol ethers using the new resin with imines were demonstrated in the presence of a Lewis acid, and it was shown that the yields using CMPP resin were much higher (ca. 10–30%) than those using Merrifield resin. Graphic

Parallel synthesis using Mannich-type three-component reactions and “Field Synthesis” for the construction of an amino alcohol library

An amino alcohol library was constructed by parallel synthesis based on Mannich-type three-component reactions of aldehydes, amines, and polymersupported silyl enol ethers, followed by reductive cleavage from the supports. “Field Synthesis”, which provides an efficient method for the construction of libraries, is introduced.

Aldol reactions on solid phase. Sc(OTf) 3-Catalyzed aldol reactions of polymer-supported silyl enol ethers with aldehydes providing convenient methods for the preparation of 1,3-diol, β-hydroxy carboxylic acid, and β-hydroxy aldehyde libraries

Abstract Aldol reactions on solid phase have been achieved. In the presence of a catalytic amount of scandium triflate (Sc(OTf) 3 ), polymer-supported silyl enol ethers reacted with aldehydes to afford the corresponding β-hydroxy thioester derivatives, which were reduced to 1,3-diol and β-hydroxy aldehyde derivatives, or hydrolyzed to β-hydroxy carboxylic acid derivatives.

Polymer-supported silyl enol ethers. Synthesis and reactions with imines for the preparation of an amino alcohol library

Abstract Polymer-supported silyl enol ethers (thioketene silyl acetals) were prepared from chloromethyl copoly-(styrene-1%-divinylbenzene) resin. The silyl enol ethers reacted with imines in the presence of a catalytic amount of scandium triflate (Sc(OTf) 3 ) to afford β-amino thioesters, which were reduced to amino alcohols in good yields. These reactions provide a convenient method for the preparation of an amino alcohol library.