Deprotection alloc group

The readily prepared immobilized phosphoramidite could be used to efficiently synthesize oligodeoxyribonucleotides with modified thymidine residues. Whereas the effect of microwave irradiation on the deprotection by exposing the strand to tet-rakis-triphenylphosphine palladium(O) and diethylammonium bicarbonate was only small using dichloromethane as solvent, complete removal of the alloc group was achieved in N,N-dimethylformamide within 10 min at 80 °C (Scheme 7.30). After the reaction, the solid-supported product was washed with N,N-dimethylformamide and dichloromethane and dried, before being subjected to acylation. The coupling... 

Deprotection of the A -alloc group of A -imidazoline 1056 with Pd(PPh3)4 catalyst gives cleanly the desired product 1075 if a basic allyl acceptor is used. In contrast, a mixture of 1057 and 1058 is formed when the acidic allyl acceptor dimedone is used (Scheme 254) <1997TL4359>. 

Another instance for this linker class is the safety-catch linker by Lyttle, which was developed for the synthesis of nucleic acids on solid supports [62]. Starting from a resin carrying an Alloc-protected amino group fragment, conventional phosphoramidite chemistry was carried out to build up the desired immobilized nucleotide 57. Removal of the Alloc group via palladium catalysis under neutral conditions produces a polymer-bound intermediate 58 with a free amino functionality that can intramolecularly attack activated phosphonates and liberate the nucleotide 59 from the solid support (Scheme 16.14). More examples of safety-catch linkers that use the deprotection of an N-functionality as the activation step are listed in Table 16.1 (resins 61-65) [63-68]. 

The allyl ester protection offers a similar approach (86-88) to that of OTmse esters. However, its removal requires the use of a complex cleavage mixture typically Pd(PPh3)-DMSO-THF-0.5 M aqueous HCl-4-methyl-morpholine over 2 h (89). Care must be taken as the deprotection mixture is hazardous and air sensitive. It should be noted that Protocols 20 and 21 outlined below can be applied for the on-resin deprotection of the N-Alloc group. 

Alloc-protected amines to directly convert them to new amine derivatives. Albericio and Barany have also used a mixture of DMSO, THF, 0.1 N HCl, and A-methyhnorpholine (2 2 1 0.1) to deprotect Alloc from resin-bound peptides that also contain base-sensitive Fmoc groups.f i ... 

Scheme 5-9. Deprotection of an alloc group on solid supports. " NMM ...

The reaction mechanism (Scheme 6.25) involves formation of a cationic 7t-allylpalladium complex by the oxidative addition of the substrate onto the catalyst. In case of a dimethylallyloxycarbonyl protecting group this step is disfavoured compared to Alloc and therefore the removal of dimethylallyl groups is slower or requires more catalyst. Accordingly, in homogeneous CH3CN/H2O solutions deprotection of (allyl)phenylacetate proceeded instantaneously with 2 mol % [Pd(OAc)2]/TPPTS while it took 85 min to remove the dimethylallyl group (cinnamyl is an intermediate case with 20 min required for complete deprotection). The reactivity differences are... 

A SPOS approach to DNA synthesis was reported very recently. It involves a ten-step synthesis of a phosphoramidite building block of I -aminomethylthymidine starting from 2-deoxyribose [46]. Microwave-mediated deprotection of a corresponding N-allyloxycarbonyl (alloc-) protected nucleoside and acylation with the residue of pyrene-l-ylbutanolic acid (pyBA) were described (Scheme 16.25). Removal of the alloc protecting group was achieved on a support (controlled pore glass, cpg) under microwave conditions (80 °C, 10 min) to ensure full conversion. 

Treatment with excess trifluoroacetic acid furnished the (dihydroiminoethano) carbazole 107 in 71% overall yield. Epoxidation of the alkene followed by a two-step protecting group modification gave epoxide 108, which underwent an oxidative epoxide opening followed by silyl protection to give silyl ether 109. Alloc deprotection, alkylation with (Z)-2-iodo-2-butenyl tosylate, followed by an intramolecular Heck reaction delivered pentacyclic diamine 110. A three-step formation of the p-ketoester 111 followed by a three-step reduction process afforded ester 112, which underwent a reduction and deprotection sequence to provide minfien-sine (99). A sequential catalytic asymmetric Heck-(V-acyliminium ion cyclization for the delivery of the enantiopure 3,4-dihydro-9a,4a-(iminoethano)-9//-carbazole is the highlight of the synthesis. 

When the N-alloc protecting group of primary amines such as benzylamine is cleaved rapidly imder these standard conditions in quantitative yields, the use of a 40-fold excess of diethylamine as the 7t-allyl scavenger or a five-fold excess of diethylamine in a butyronitrile/water system is necessary for the quantitative deprotection of aUoc derivatives of secondary amines. 

Allyl-based protection for the phosphate group in phosphoserine-containing peptides has also been employed. In this case, the Af-alloc-bis(allyl)phosphate of serine was incorporated into a resin-bonnd peptide using standard solid phase peptide synthesis methodology and deprotected nsing trimethylsilyl azide and tetrabutylammonium flnoride as the nucleophile (Scheme 10). 

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