Carboxylic tert-butyl esters

E. J. Corey and B. Samuelsson, One-step conversion of primary alcohols in the carbohydrate series to the corresponding carboxylic tert-butyl esters, J. Org. Chem., 49 (1984) 4735. 

D. 2(S)-(fl-tert-Butoxycarbonyl-a-(R)-hydroxyethyl)-4-(R)-hydroxy-pyrrolidine- 1-carboxylic acid, tert-butyl ester. The identical procedure was followed, in this case using the (,S)-BINAP catalyst (5)-l. Hydrogenation is conducted for 64 hr, and the reaction mixture is then transferred to a 250-mL, round-bottomed flask and concentrated to dryness. The residue is dissolved in 17 mL of methanol and cooled to 15°C. After the slow addition of 7 mL of DI water, the solution is aged for 15 min gradually forming a thin slurry. More DI water (75 mL) is added over 1 hr and the mixture is allowed to stand for an additional 1 hr at 15°C. The resulting crystals (Note 19) are filtered at 15°C, washed with 10 mL of 1 4-MeOH water, and then dried overnight in a vacuum oven (35°C, 686 mm) to yield 7.0 g (70%) of (R)-hydroxy ester 4b (Note 20). 

S-4R)-2-tert-Butoxycarbonylacetyl-4-hydroxypyrrolidine-l-carboxylic acid, tert- butyl ester 2-Pyrrolidinepropanoic acid, l-[(l,l-dimethylethoxy)carbonyl]-4 hydroxy- P-oxo-, 1,1-dimethylethyl... 

Carboxylic acids can be protected as oxazolines [96, 105-107, 186, 191] or as ester functions. Alkynic esters such as silyl esters [153, 211], tert-butyl esters [216], and even benzyl esters [153, 211] have been successfully hydrozirconated when the reactive site was a terminal alkyne or vinyl group (Scheme 8-27). 

The reaction of tert-butyl esters with Et3SiH/TFA results in the reductive deprotection of the ester and formation of isobutane. The yields of the isobutane are not recorded, but the acids are obtained nearly quantitatively (Eq. 150).307 In a similar manner, the lactone shown in Eq. 151 is converted into the acid in good yield.308 In like manner, the reductive deprotection of allyl esters provides the carboxylic acids in high yields.270... 

FIGURE 3.9 Deprotection of carboxyl groups by base-catalyzed hydrolysis of (A) esters and (C) trifluoroacetamides, involving direct attack by the hydroxide anion. (B) tert-Butyl esters are resistant to saponification. 

The tert-butyl esters of 2-pyrrolylaminomethylenemalonates (1438, R2 = COO/Bu) were selectively hydrolyzed with methanesulfonic acid or concentrated sulfuric acid at 0°C or at ambient temperature to afford the corresponding carboxylic acids (1438, R2 = COOH) in 26-98% yields. The carboxylic acid (1438, R = Me, R1 = H, R2 = COOH) underwent facile decarboxylation upon heating at 190-200°C to give 2-pyrrolylamino-methylenemalonate (1438, R = Me, R1 = R2 = H) in 73% yield (85JHC1429). 

V"-Boc-7Va -Z-L,L-diaminosuberic acid co-tert-butyl ester or bis(7V"-Boc)-L,L-diaminosuberic acid synthesized by the mixed Kolbe electrolytic carboxylative dimerization method was successfully utilized in the synthesis of nonreducible bicyclic analogues of somatostatin1491 or hematoregulatory peptide (pGlu-Glu-Asp)2-Dsu-(Lys)2, respectively.[50]... 

The synthesis of pyrazolidine-2-carboxylic acid containing peptides is carried out following the standard procedures established for azaamino acid peptides as described in Section 10.4. Accordingly, l-(/< rt-butoxycarbonyl)pyrazolidine (which is the equivalent of 2-azaproline tert-butyl ester) is treated with 4-nitrophenyl chloroformate to generate (/ert-butoxy-carbonyl)pyrazolidine-2-carboxylic add 4-nitrophenyl ester.1 60 This active ester is then used... 

The m- and p-APha isomers are commercially available. The synthesis of Boc-o-APha-OH and its ethyl and tert-butyl esters by carboxylation of the dianion of Boc-o-methylaniline has been briefly mentioned. 63 Whereas the carboxy group in APha is expected to react normally, the aromatic amino function is expected to be less nucleophilic owing to the delocalization of the nitrogen lone pair. However, deactivation should be less significant than in o- and p-Abz. Only a few hints at this conclusion may be found in the literature. Indeed, coupling of Boc-p-APha-OSu to an aliphatic primary amine was conducted in DMF for 2 h, affording the amide in a 75% yield. 64 ... 

Figure 3 describes the preparation of A-co-undecenoyl-L-valine CSP bonded to silica gel. The carboxylic acid group of L-valine was protected by the reaction with isobutylene using the method of Roeske [47]. The formed tert-butyl ester of L-valine was precipitated from diethyl ether as the oxalate by the dropwise addition of a solution of 10% oxalic acid in absolute ethanol. The precipitate is dried and the oxalate group is removed by the reaction of sodium hydroxide. The tert-butyl ester of L-valine was treated with undecenoic acid in tetrahydrofuran (THF), which resulted in A-co-undecenoyl-L-valine methyl ester. In another step, lOmM of monochlorosilane was dissolved in 20 mL of dry pyridine and was allowed to react with /V -to - u ndccenoyl-L-valine methyl ester. 

The group of Jew and Park successfully utilized dihydrocinchonidine-derived 6f as an efficient catalyst for the asymmetric alkylation of o-biphenyl-2-oxazoline- and o-biphenyl-2-thiazoline-4-carboxylic acid tert-butyl esters (16a and 16b) under mild solid-liquid phase-transfer conditions (Scheme 2.13) [32,33]. These reactions are... 

The catalytic and chiral efficiency of (S,S)-le was also appreciated in the asymmetric synthesis of isoquinoline derivatives, which are important conformationally constrained a-amino acids. Treatment of 2 with a,a -dibromo-o-xylene under liquid-liquid phase-transfer conditions in the presence of (S,S)-le showed complete consumption ofthe starting Schiffbase. Imine hydrolysis and subsequent treatment with an excess amount of NaHCOs facilitated intramolecular ring closure to give 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester 38 in 82% yield with 98% ee. A variety of l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives possessing different aromatic substituents, such as 39 and 40, can be conveniently prepared in a similar manner, with excellent enantioselectivity (Scheme 5.20) [25]. 

Jew and Park achieved a highly enantioselective synthesis of (2S)-a-(hydroxy-methyljglutamic acid, a potent metabotropic receptor ligand, through the Michael addition of 2-naphthalen-l-yl-2-oxazoline-4-carboxylic acid tert-butyl ester 72 to ethyl acrylate under phase-transfer conditions [38]. As shown in Scheme 5.36, the use of BEMP as a base at —60 °C with the catalysis of N-spiro chiral quaternary ammonium bromide le appeared to be essential for attaining an excellent selectivity. 

The above drawbacks of crystalline photoreactions are circumvented in an approach called the ionic auxiliary approach which is outlined below [185-207]. Scheffer and coworkers make a salt of a substrate having a carboxylic acid with a chiral organic amine or vice versa. The chirality of the amine would necessitate that the salt crystallize in a chiral space group. The crystal formed in this fashion would also be able to withstand higher conversions due to stronger lattice forces in these crystals. An example of this type of approach is shown in Scheme 8. Treatment of the dibenzobarralene derivative 18, with the tert-butyl ester of (S)-proline 19, afforded salt 20 irradiation of the crystals of this salt gave diester 21. In this reaction, only one regioisomer 21 is formed, and this product is formed in over 95% ee. More examples are to be found in Chap. 12. 

Condensing racemic l,2-methano[70]fullerene-71-carboxylic acid obtained by hydrolysis of its tert-butyl ester (( )-260, Scheme 1.25),243 with an amino derivative of zinc tetraphenylporphyrin, Imahori, Yamazaki, Sakata, and coworkers synthesized a C7o-containing dyad.355,446 Comparison with the C60-analogue showed that photoinduced electron transfer from the singlet excited Zn-porphyrin to the fullerene is faster in the C70 derivative. 

During a synthesis of the protein kinase C inhibitor Balanol. Lampe and co-workers77 found that deprotection of the tert-butyl ester 30.1 [Scheme 6.30] with trifluoroacetic or formic acid was accompanied by substantial quantities of a debenzylated by-product. The same side reaction accompanied thermolytic cleavage of the terf butyl ester in neutral solvents presumably due to add catalysis by the carboxylic acid product 30.2. Thermolysis in quinoline at 205 °C led cleanly to the desired benzophenone carboxylic acid 30.2 in 68% yield. 

The classical method for making tert-butyl esters involves mineral acid-catalysed addition of the carboxylic acid to isobutene but it is a rather harsh procedure for use in any but the most insensitive of substrates [Scheme 6.33].80-82 Moreover, the method is hazardous because a sealed apparatus is needed to prevent evaporation of the volatile isobutene. A simpler procedure [Scheme 6.34] involves use of tert-butyl alcohol in the presence of a heterogeneous acid catalyst — concentrated sulfuric acid dispersed on powdered anhydrous magnesium sulfate. 3 No interna] pressure is developed during the reaction and the method is successful for various aromatic, aliphatic, olefinic, heteroaromatic, and protected amino acids. Also primary and secondary alcohols can be converted into the corresponding /erf-butyl ethers using essentially the same procedure (with the exception of alcohols particularly prone to carbonium ion formation (e.g. p-... 

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