Terf-Butyl ester group

Cyclopropanation. Rhodium complexes have been extensively employed for catalytic carbenoid cyclopropanation of alkenes. In the presence of [Rh2(S-TBSP)4], treatment of 2-aryl-substituted 2//-chromenes with dimethyl diazomalonate furnished the desired cyclopropanes in good yields (eq 41). The cyclopropane product with a terf-butyl ester group underwent rearrangement upon treatment with Sn(OTf)2 to from a y-lactone. OMe... 

The disadvantage of this method is that saponification of the resulting ester group can result in racemization. A method for the synthesis of TV-methyl amino acids without esterification has been presented by Benoiton and co-workers,[78 95] which uses sodium hydride as the base and iodomethane in THF at room temperature. This method is also applicable to the synthesis of side-chain-functionalized amino acid derivatives when the side chain is protected by a terf-butyl-type group. 

For subsequent transformations, it was necessary to protect the amino and C-2 carboxyl groups of fra/w-4-hydroxy-L-proline 34. Throughout all of the synthetic work to be described, A-benzoyl amide protection was chosen as it was felt likely that such a functional group would be resistant to most reaction conditions. Initially, a C-2 terf-butyl ester was chosen in an attempt to maximize the stereoselectivity in the planned enamine alkylation reaction however, later experiments revealed that the more straightforward to introduce C-2 methyl ester was equally effective. The preparations for all of the derivatives used are described here. 

The synthesis of the oxazole compound 45 starts with the coupling of the N-protected (/ )-methylcysteine compound 18 with threonine terf-butyl ester using bis(2-oxo-3-oxazolidi-nyl)phosphinyl chloride (BOP-Cl) [15] as a coupling reagent. Jones oxidation of the threonine hydroxy group leads to the ketoamide 44. The desired oxazole ring is closed by treatment with thionylchloride/pyridine. After deprotection, the oxazole, compound 45 is obtained. In the next step the oxazole compound 45 is coupled with the tris(thiazoline) compound 43 to yield the thioester 46. Now Fukuyama closes the fourth and last thiazoline ring (46 47). After conversion of the carboxylic acid function into a methyl-... 

The 9-fluorenylmethoxycarbonyl group is another distinguished contribution from the Carpino laboratory198199 to the solution-phase synthesis of peptides and latterly it has been adapted to solid-phase peptide synthesis too.200 The Fmoc group is exceptionally stable towards acid thus, carboxylic acids can be converted to acid chlorides with thionyl chloride201 or terf-butyl esters using sulfuric acid and isobutene.202 Furthermore, Fmoc groups are unscathed by HBr in... 

The classical method for tert-butyl esterification involves nnineral add catalyzed addition of the amino acid to isobutene. Both, N-protected, e.g. Z-Xaa-OH, and unprotected amino acids form tert-butyl esters with isobutene in the presence of catalytic amounts of sulfuric acid or TosOH. " Another efficient method is the transesterification of an acetic acid tert-bvXy ester catalyzed by perchloric acid. " Amide tert-butylation was recognized as a side reaction in the presence of perchloric acid, but could be completely suppressed by using sulfuric acid. Both methods, acid-catalyzed addition to isobutene and the transesterification of acetic add terf-butyl esters, result in simultaneous terf-butyl-ation of hydroxy and sulfanyl groups. A synthetic route to Z-Thr-OtBu, Z-Ser-OtBu, and Z-Hyp-OtBu without conconnitant O-alkylation involves the hydroxy protection by the acetoacetyl group, which is readily cleaved by treatment with 2 equivalents of hydrazine in EtOH for 30 minutes. ... 

Besides the benzyl ethers (Section 2.6.4.1.1.1), which are stable toward normal acidic conditions, acid-labile ethers have been developed. terf-Butyl ethers can be cleaved under conditions used for cleavage of terf-butyl ester and Boc groups, while triphenylmethyl ethers can be cleaved under very mild acidic conditions. 

Acetals and ketals have attracted a great deal of attention recently as protecting groups of PHOST due to their lower activation energies of deprotection than fBOC and terf-butyl esters. While the majority of chemical amplification resists require PEB to accelerate acid-catalyzed reactions, deprotection of ac-... 

A new type of copolymer resist named ESCAP (environmentally stable chemical amplification photoresist) has recently been reported from IBM [163], which is based on a random copolymer of 4-hydroxystyrene with tert-butyl acrylate (TBA) (Fig. 37), which is converted to a copolymer of the hydroxystyrene with acrylic acid through photochemically-induced acid-catalyzed deprotection. The copolymer can be readily synthesized by direct radical copolymerization of 4-hydroxystyrene with tert-butyl acrylate or alternatively by radical copolymerization of 4-acetoxystyrene with the acrylate followed by selective hydrolysis of the acetate group with ammonium hydroxide. The copolymerization behavior as a function of conversion has been simulated for the both systems based on experimentally determined monomer reactivity ratios (Table 1) [164]. In comparison with the above-mentioned partially protected PHOST systems, this copolymer does not undergo thermal deprotection up to 180 °C. Furthermore, as mentioned earlier, the conversion of the terf-butyl ester to carboxylic acid provides an extremely fast dissolution rate in the exposed regions and a large... 

The transfer hydrogenation of ketones was subsequently attempted, although for these more challenging substrates chiral primary amines such as L-valine terf-butyl ester were required in order to obtain good yields (68-99%) and enantioselectivities (70-98% ee) [168]. The reaction most likely involves an iminium-phosphate hydrogen bond. Another important application of asymmetric counteranion-directed catalysis developed by the List group is the chiral phosphate anion-directed epoxidation of a, 3-unsamrated carbonyls [169]. 

A soln. of carbobenzoxy-L-proline p-nitrophenylester and tert-huiy leucinate in methylene chloride allowed to stand 48 hrs. at room temp. ferf-butyl carbobenzoxyprolyl-L-leucinate. Y 96%.—terf-Butyl esters are particularly useful in peptide synthesis, because the ester group can be removed by acid catalysis (s. Synth. Meth. 15, 12) and thus side reactions encountered in alkaline hydrolysis avoided. Other advantages arise from the stability of amino acid and peptide tert-butyl esters as free bases, particularly in allowing their storage. F. use, prepn., and hydrolysis of tert-butyl esters s. G. W. Anderson and F. M. Callahan, Am. Soc. 82, 3359 (1960) peptides from p-nitrophenyl esters s. a. J. Meienhofer and V. du Vigneaud, Am. Soc. 83, 142 (1961) B. Liberek, Chem. Ind. 1961,987. 

Exposure of compound 16, a substance that can be obtained in a straightforward manner from glycine, to sodium tert-butoxide furnishes an enolate that undergoes conversion to 8 upon treatment with terf-butyl formate. It was anticipated that the phthalimido and tert-butyl ester protecting groups in 8 could be removed easily and selectively under anhydrous conditions at a later stage in the synthesis. 

Peroxy esters 67 were prepared in situ by the reaction of phosphonochloridate and terf-butyl hydroperoxide in diethyl ether. The peroxy ester 67 (R = Ph) is stable for several days at 5 °C in diethyl ether. Most peroxyphosphates 67 with an RO group other than ferf-butylperoxy are unstable even for short periods . This synthetic method was successfully applied for synthesis of ring peroxyphosphates 70 and 71 as colorless oils. They are very unstable and decompose at 25 °C to yield polymeric products and volatile side products . ... 

Schotten-Baumann type N-benzoylation was carried out on trans-4-hydroxy-L-proline 34,39 giving amide 43 in a satisfactory yield of 65%. The disappointing yield here could be attributed to difficulties experienced in recrystallization of the product 43. The amide 43 was esterified to give tert-butyl ester 44 using a modification of a procedure described by Widmer40 with dimethylformamide-dineopentyl acetal and tert-butanol as reagents. This provided crystalline 44 in 71% yield from 43 with no evidence of terf-butyl ether formation at the C-4 hydroxyl group (Scheme 12). 

The acetal is probably formed by hydride transfer to an intermediate ester. The terf-butyl group apparently stabilizes the second intermediate and consequently changes the course of the reaction. It should be noted that the first cyclic intermediate is stabilized by coordination of the borane with the oxygen of the carbonyl. The results are outstanding when = Me (92-98 %), although selectivity and yield (45-62 %) decrease when R = H (Eq. 48). 

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