Specific Solvation as a Tool for the <i>N</i>‐Chemoselective Arylsulfonylation of Tyrosine and (4‐Hydroxyphenyl)glycine Methyl Esters

Penso, Michele; Albanese, Domenico; Landini, Dario; Lupi, Vittoria; Tricarico, Giovanni

doi:10.1002/ejoc.200300366

Cited by 12 publications

(9 citation statements)

References 14 publications

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“…A different reaction outcome was observed in THF (entry 3), in which the target product 2a was formed in low yield as the sole detectable product. This solvent was thus selected as the major component of specific solvating mixtures as illustrated in our preceding reports 3,4. The model reaction was operated in THF containing molar amounts of either DMF (2.6 mol DMF per mol 1a ) or DMSO (2.8 mol DMSO per mol 1a ) (entries 4–7).…”

Section: Resultsmentioning

confidence: 99%

“…These strategies can be summarized in three broad categories: (a) Protection of one specific functional group, (b) simultaneous transformation of all reactive centers, then restoration of one of the centers, or (c) activation of the target group and/or deactivation of groups that should remain unaltered 2a. Previously, we applied the activation/deactivation approach to the N ‐alkylation of substrates that contain nucleophilic N,O‐centers such as 2‐hydroxycarbazole,3 tyrosine,4,5 serine and threonine (2‐nitrobenzene)sulfonamido esters 6. Under the reaction conditions applied, both functions were deprotonated by an inorganic base, with formation of the corresponding dianion.…”

Section: Introductionmentioning

confidence: 99%

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Chemoselective Synthesis of N‐Protected Alkoxyprolines under Specific Solvation Conditions

et al. 2014

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N‐Protected hydroxyprolines (Hyp) were transformed chemoselectively into alkoxyproline derivatives by direct O‐alkylation. The starting Hyp was transformed into the corresponding dianion in a mixture of dimethyl sulfoxide and tetrahydrofuran (1:16 v/v) as solvent. Under these conditions, the carboxy‐anion showed reduced nucleophilicity because it was specifically solvated, and the more reactive oxy‐anion was selectively alkylated. N‐Protected trans‐4‐alkoxy‐, cis‐4‐alkoxy‐ and trans‐3‐alkoxyprolines were thus obtained in a single step in very high overall yields and with complete stability of the stereogenic center configuration.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemoselective Synthesis of N‐Protected Alkoxyprolines under Specific Solvation Conditions

et al. 2014

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“…Thus, the amino acid 3 was first esterified by treatment with hydrogen chloride in methanol. [9] The salt 4 thus obtained was allowed to react with an excess of phenylmagnesium bromide to give aminoethanol 5 in 48 % overall yield.…”

Section: Resultsmentioning

confidence: 99%

“…[14] (R)-4-Hydroxyphenylglycine methyl ester hydrochloride (4) was prepared from 3 in quantitative yield as described in ref. [9] (R)-2-Amino-2-(4-hydroxyphenyl)-1,1-diphenylethanol (5) A 500-mL three-necked flask was equipped with a pressureequalizing dropping funnel, a reflux condenser with a connection to the combined nitrogen/vacuum line and a magnetic stirrer. The flask was charged with magnesium turnings (14.6 g, 0.60 mol) and a few crystals of iodine and closed with a septum.…”

Section: Experimental Section General Remarksmentioning

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4‐Hydroxyphenylglycine‐Based Oxazaborolidines for Enantioselective Reductions of Ketones

2007

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Amino alcohols 6 featuring the diphenylhydroxymethyl group are prepared from the commercial amino acid (R)-4-hydroxyphenylglycine 3. Oxazaborolidines generated in situ from the amino alcohols 6 and borane-dimethyl sulfide serve as catalysts in enantioselective reductions of acetophenone. The para-substituents of the phenyl ring at the stereogenic carbon atom have a substantial influence on the enantioselectivity. When mediated by the nonaflate 6d, the reduction of ketones 7, 9, 11, and 13 leads to the carbinols 8, 10, 12, and 14 in 90 to 96 % ee.

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“…, MeCN, 25-80 °C; ii) R 2 X (2), K 2 CO 3 (anhyd) , The nosylamido ester 9 and several arylsulfonamido esters of tyrosine were prepared from the corresponding a-amino acid esters under SL-PTC conditions without protecting the phenolic hydroxy group. 10 As a representative example (Scheme 2), the methyl tyrosinate 8 was made to react with nosyl chloride, in the presence of lyophilized sodium carbonate, by using a THF-DMF mixture as solvent. The highest chemoselectivity of N-arylsulfonylation and sulfonamido ester 9 yield were reached in the presence of a small amount of DMF (2.6 mol/mol of substrate), because this highly ion-coordinating solvent preferentially solvates the [phenoxide/sodium] ion pairs and decreases the charge and hence the nucleophilicity of the oxy-anion.…”

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Chemoselective N-Alkylation of Di-N,O-protected Tyrosine through Specific Oxy-Anion Solvation by Non-Hydrogen Bonding Donor Solvents

Penso¹,

Albanese²,

Landini³

et al. 2006

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activated L-tyrosine methyl ester has been directly N-alkylated under solid-liquid phase-transfer catalysis (SL-PTC) conditions and in a coordinating non-hydrogen bonding donor (non-HBD) solvent, which reduces through specific solvation the nucleophilicity of the oxy-anionic center of the N,O-dianion formed by action of an anhydrous inorganic carbonate.Mono-N-alkylated a-amino acid derivatives are a class of exciting products, both as pharmacologically active compounds 1 and as starting materials for the construction of peptidomimetics. 2 Among the N-alkyl-a-amino acids preparations, 3 Fukuyama's amine protocol stands out for its mild reaction conditions, simplicity and broad range of applications. 4 Bowman and Coghlan 5 utilized this procedure for the N-alkylation-deprotection of a limited number of 2-(2-nitro-benzenesulfonylamino) carboxylic esters, using organic bases under homogeneous conditions. In a subsequent paper, 6 we reported that solidliquid phase-transfer catalysis (SL-PTC) 7 permitted remarkable improvements on both times and yields of the N-alkylation reactions for a wider series of a-nosylamido esters (Scheme 1). In particular, esters 1 derived from glycine or amino acids bearing in their side chain either a phenyl or an alkyl group (R 1 = Ph, Alkyl), reacted in a chemo-and stereoselective fashion with alkyl halides 2 under SL-PTC conditions, using acetonitrile as a solvent (Scheme 1), and the corresponding N-alkyl-a-nosylamido esters 3 were obtained in excellent yields (80-96%). The alkylation reactions of a-nosylamido-b-hydroxy esters 4 (Scheme 1), derived from serine (R 3 = H) and threonine (R 3 = Me), were less chemoselective. In fact, the aliphatic hydroxy group under these conditions competes with the nosylamide for the nucleophilic attack, and significant amounts of the corresponding substituted a-nosylamido acrylic esters 7 were formed by 1,2-elimination of an alcohol unit (R 2 OH) from the unstable di-N,O-alkylated intermediates 6. The substitution of DMF for acetonitrile improved the N-alkylation chemoselectivity of compounds 4, and products 5 were isolated in good yields (76-86%). 5In view of these results, we guessed that the alkylation reactions of sulfonamido esters derived from a-amino acids containing a phenol unit (10 5 -10 6 times more acidic than an aliphatic OH) in their side chain would be knottier. In fact, due to the close acidity values of the aromatic hydroxy group and of the nosylamido group 8 (pk a ca. 10-11, relative to water), 9 the simultaneous deprotonation of both these functions, and the consequent competition between the two nucleophilic centers of the formed N,O-dianion, are expected. With the aim of investigating the behavior of these compounds in the nucleophilic substitution reactions and producing N-alkyl-tyrosine derivatives, an interesting class of new multifunctionalized molecules, we have chosen as a model the methyl ester of L-N-(2-nitrobenzenesulfonyl)tyrosine (9, Scheme 2). Scheme 1 N-Alkylation of a-nosylamido esters 1 and 4 under SL-PTC conditions.

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Specific Solvation as a Tool for the N‐Chemoselective Arylsulfonylation of Tyrosine and (4‐Hydroxyphenyl)glycine Methyl Esters

Cited by 12 publications

References 14 publications

Chemoselective Synthesis of N‐Protected Alkoxyprolines under Specific Solvation Conditions

Chemoselective Synthesis of N‐Protected Alkoxyprolines under Specific Solvation Conditions

4‐Hydroxyphenylglycine‐Based Oxazaborolidines for Enantioselective Reductions of Ketones

Chemoselective N-Alkylation of Di-N,O-protected Tyrosine through Specific Oxy-Anion Solvation by Non-Hydrogen Bonding Donor Solvents

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