Allyl ester, removal

The Noc group, developed for amino acid protection, is introduced with the acid chloride (Et3N, H2O, dioxane, 2 h, 20°, 61-95% yield). It is cleaved with Pd(Ph3P)4 (THF, A, A -dimethyibarbituric acid, 8 h, 20°, 80% yield). It is not isomerized by Wilkinson s catalyst, thus allowing selective removal of the allyl ester group. 

Cyclization of quinoline derivatives 57 in DMSO under the action of Cs2C03 at 85 °C afforded diesters 49 <1995T11125>. No cyclization product could be obtained when a piperazino group was present in 57 (Rz = piperazino). Cyclization in the presence of NaH gave a lower yield. When the potassium salt of 57 was used in the presence of 20 mol% of Cul, the conversion was almost quantitative, but the removal of the last traces of copper was difficult. When allyl ester 57 (R = Et, R1 = allyl, R2 = 4 - 7/-biu o ycarbonyl-l -pipcridinyl) was cyclized in DMSO in the presence of Cul and KOBuc at 50-55 °C for 0.5 h, then 100-105 °C for 6 h, the 3-ester 50 (R = Et, R1 = 4-tert-butoxycarbonyl-l-piperidinyl) was obtained in 32% yield. 

The Baran group has reported an unusual deprotection of allyl esters in micro-wave-superheated water. A diallyl ester structurally related to the sceptrin natural products (see Scheme 6.87) was cleanly deprotected at 200 °C within 5 min (Scheme 6.168) [181]. Other standard deprotection transformations carried out under microwave conditions, specifically N-detosylations [317], trimethylsilyl (TMS) removal [318, 319], and N-tert-butoxycarbonyl (Boc) deprotection [231], are summarized in Scheme 6.169. 

Products of this type were not isolated, however, when the non-immobilised metathesis substrates were allyl esters or ethers. In these cases, the combined effect of metathesis and TFA cleavage was simply to remove the allyl group. A modified protodesilylation mechanism was proposed to account for these results (Scheme 3). 

Resins 2 and 3 are treated with dichloromethane containg 3% and 1.5% trifluoroacetic acid (lOmL/g resin), respectively, for 18 h. The resin is filtered off and washed twice with dichloromethane (10 mL / g of resin). The filtrate is washed with saturated NaHCCL (5 mL) and brine (5 mL), and the organic phase is separated and filtered through a short path silica gel column to obtain a colourless solution. In the case of polymer-bound allyl esters giving rise to cleavage products of type 5f, the aqueous workup is omitted. The products obtained after removal of solvent under reduced pressure contain small amounts of silanol by-products (note 5), which is to be accounted for in the calculation of cleavage yields. 

The noteworthy advantages of the allyl ester are (a) it is readily introduced into amino acids (b) after isomerization (to 1-propenyl) by a palladium(O) catalyst it may be removed under weakly acidic or basic and neural conditions (32), even if sulfur-containing amino acids are present (34) (c) it shows orthogonal stability to the tert-butyloxycarbonyl and 9-fluorenylmethoxy-carbonyl groups (10) and (d) it is not affected by the hydrogen fluoride-pyridine complex (35). 

The synthesis were effected with the appropriate glycosylated derivatives of L-threonine (135 and 136). Selective removal of the allyl ester derivative... 

The allyl ester [22] can be selectively removed in the presence of Z- [22], Boc- [25,28], or Fmoc amino protection [24]. For example, Fmoc threonine allyl ester 24 was glycosylated with 2-azido-3,4,6-tri-0-acetyl-2-deoxy-a-D-galactopyranosyl bromide 25 [6] to give the conjugate 26 in high yield [24]. Separation of the a-anomer and transformation of its... 

PPhj)4 as an electron transfer catalyst (Scheme 2-20)3S). Thus, the electroreductive removal of the allyl group from cephalosporin allyl esters 55 yields the corresponding acids 56 in 72% yield. 

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