Alloc protection

Scheme 5 Allylation of Alloc-derived sulfones and ring-closing metathesis of an Alloc-protected homoallylic amine...

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

Removal of Alloc Protecting Group from Resin 10 or 19... 

In a reversed approach, N -Ras lipidated peptides were synthesized in solution via an Sjv2 displacement of bromoalanine containing hexapeptides with thiopalmitic acid and farnesylmer-captane as nucleophiles (26). The synthetic route started with the dipeptides and tetrapeptides A(Br)M and GLPA(Br), both incorporating bromoalanine. After farnesylation of the C-terminal tetrapeptide, it was coupled to the N -Alloc protected dipeptide. This farnesylated hexapeptide was then treated with thiopalmitic acid for flnal pahnitoylation. 

The alloc protective group is cleaved by palladium providing a secondary amine, which is alkylated by (Z)-2-iodo-2-butenyl tosylate to give the corresponding vinyl iodide in 96 % yield. The latter vinyl... 

The conversion of the BOC group to other carbamates is achieved by heating with an alcohol, Ti(0-i-Pr)4 in toluene. Teoc-, Cbz- and Alloc-protected primary amines have been prepared in this fashion. The reaction is selective for a primary BOC derivative probably because the reaction proceeds through an isocyanide. ... 

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 N protecting group is cleaved by the appropriate patented method, (ref. 4). For the cleavage of the N-ALLOC protecting group, the drying step can be avoided. 

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. 

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. 

Remove the tag protecting group and couple the first code as the Alloc-protected versions. ... 

Although these derivatives offer great potential for highly site specific manipulations, their use in carbohydrate chemistry has been somewhat limited mainly because the procedures and strategies based on the classical protecting groups are tried and tested. Of these, probably the widest use has been made of Alloc protection because this provides a convenient route to allyl ethers (see section 2.3.2, Allyl ethers). 

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 ... 

The deprotection of Alloc-protected amines can also be accomplished in aqueous media employing the water-soluble phosphine TPPTS and excess diethylamine as the nucleophilic scavenger.i Secondary amines have also been successfully deprotected with no competing A-allylation using biphasic conditions in conjunction with Pd(OAc)2, TPPTS and excess diethylamine. ... 

Removal of alloc protection under such conditions leaves intact other protective groups, which would have been attacked if the deprotection were done by conventional techniques based on hydrogenolysis or solvolysis. Moreover, the conditions can be finely adjusted to allow selective differential deprotection of similar protective groups, differing only by steric bulk (Scheme 66). This technique has been applied for peptide synthesisJ ... 

Scheme 20. In situ deprotection and peptide coupling with Alloc-protected amines. ...

Palladium-catalyzed Deprotection Processes. Several palladium-catalyzed and mild methods for the deprotection of various functional groups have been developed. For example, a system for the conversion of hydrazones into the corresponding carbonyl compounds that is catalytic in both Pd(OAc)2 and SnCl2 has been reported, as has a procedure for the Pd(OAc)2-catalyzed cleavage of allyloxycarbonyl (Alloc) protected alcohols. ... 

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