Protective groups sulfonates

Sulfonate protective groups have been restricted largely to carbohydrates where they serve to protect the 2-OH with a nonparticipating group so that coupling gives predominantly 1,2-cw glycosides. 

Polymer supported reagents, catalysts, protecting groups, and mediators can be used in place of the corresponding small molecule materials (Sherrington, 1991 Sundell and Nasman, 1993). The reactive species is tightly bound to a macromolecular support which immobilizes it. This generally makes toxic, noxious, or corrosive materials much safer. The use of polystyrene sulfonic acid catalyst for the manufacture of methyl r-butyl... 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

Phenylthioethyl has been used as a protecting group for N-3 of thymidine during manipulation of the sugar. It was removed via oxidation to the sulfone <06SL845>. 

The monomer/oligomer mixtures were used In the third step of the reaction sequence, the replacement of bromine with 2-methyl-3-butyn-2-ol by use of the bls(trlphenylphosphlne) palladium chloride catalyst system. This reaction used a trlethylamine/pyridine solvent system to replace the bromines on the ether sulfone with ethynyl groups protected by acetone adducts. The acetone protecting groups were then removed In a toluene/methanol/potasslum hydroxide solvent system. 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

The sulfonated atropisomeric bisphosphine MeOBIPHEP (48) was prepared in a Grignard reaction of the appropriate bisphosphonic dichloride and p-indolylsulfonamido-bromobenzene followed by reduction of the phosphine oxide with HSiCU [52]. The indolylsulfonyl protecting group was... 

A further eight steps were required to convert the cyclopentanone 52 into the sulfone 59 that was deprotonated and treated with an allylic bromide (60) to afford the alkylated sulfone 61 (Scheme 7). The sulfone moiety and the benzyl ether protecting group were reductively removed in a one-pot procedure to afford a mono-protected diol (62). 

Scheme 12 Functional and protecting group transformations and a sulfone alkylation for chain elongation...

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

L = Sulfonate esters or phosphonate esters 44 L = Carbonates and carbamates Scheme 26 Photoremovable protecting groups 33, 43, and 44. 

In a synthetic application of this double inversion sequence, tris(benzyloxy)bromo boronic ester 6 obtained in the ribose sequence (Section 1.1.2.1.3.2.) is converted to the 4-methoxyphenyl-methoxy derivative 7 in the usual way. 2,3-Dichloro-5,6-dicyano-l,4-benzoquinone cleaves the protecting group to furnish the a-hydroxy boronic ester 8. Conversion of the a-hydroxy boronic ester 8 to the methanesulfonate 9 followed by displacement of the sulfonate by phenylmethoxide yields a-benzyloxy boronic ester 10, which is a diastereomer of one of the ribose intermediates37. 

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