Rapid access to N -Boc phenylglycine derivatives via benzylic lithiation reactions

Abstract-The scope of nickel boride mediated reduction of nitriles has been extended further to allow the preparation of Boc protected amines via a mild catalytic process. It is noteworthy that the toxicity of this procedure is greatly reduced due to its catalytic nature in nickel(II) chloride used in combination with excess sodium borohydride. The protocol is marked by its resilience towards air and moisture and hence an easy and general practical protocol. q

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“…21 Spectroscopic data corresponds to that reported in the literature. 42 Spectroscopic data corresponds to that reported in the literature. 42 …”

Section: Phenethyl-carbamic Acid Tert-butyl Ester (2b)supporting

confidence: 83%

A Generic Approach for the Catalytic Reduction of Nitriles.

et al. 2003

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“…Evaporation of the solvent gave N -Boc-α-amino acid 2 or 4 . N -Boc-phenylglycine (2-( tert -butoxycarbonylamino)-2-phenylacetic acid: 2a ; 207 mg, 83%), − N -Boc-4-methylphenylglycine (2-( tert -butoxycarbonylamino)-2-(4-methylphenyl)acetic acid: 2d ; 200 mg, 75%), N -Boc-2-fluorophenylglycine (2-( tert -butoxycarbonylamino)-2-(2-fluorophenyl)acetic acid: 2e ; 186 mg, 69%), N -Boc-4-fluorophenylglycine (2-( tert -butoxycarbonylamino)-2-(4-fluorophenyl)acetic acid: 2f ; 188 mg, 70%), , N -Boc-4-chlorophenylglycine (2-( tert -butoxycarbonylamino)-2-(4-chlorophenyl)acetic acid: 2g ; 200 mg, 70%), N -Boc-4-methoxyphenylglycine (2-( tert -butoxycarbonylamino)-2-(4-methoxyphenyl)acetic acid: 2l ; 203 mg, 72%), N -Boc-cyclohexylglycine (2-( tert -butoxycarbonylamino)-2-cyclohexylacetic acid: 4a ; 132 mg, 51%), and N -Boc-homophenylalanine (2-( tert -butoxycarbonylamino)-4-phenylbutanoic acid: 4b ; 121 mg, 43%) are known compounds.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of N-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation of N-Boc-α-aminosulfones

et al. 2021

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Electrochemical reduction of N-Boc-α-aminosulfones in DMF using an undivided cell equipped with a Pt plate cathode and an Mg rod anode under atmospheric pressure of bubbling carbon dioxide through the solution under constant current conditions resulted in a reductive C–S bond cleavage with elimination of benzenesulfinate ion generating the corresponding anion species followed by fixation of carbon dioxide to give the corresponding N-Boc-α-amino acids in moderate to good yields.

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“…Examples of lithiations of the three parent Nacylbenzylamines of interest are shown in Table 5. [63][64][65][66][67][68][69] All three substrates are lithiated readily by s-BuLi or t-BuLi at low temperature, but in contrast to the situation when the urea group is attached directly to the ring, lithiation does not occur to any significant extent on the N-methyl groups. Also, for substrates 63-65 there is a clear trend in the regioselectivity of lithiation as the DMG is varied.…”

Section: Effect Of the Dmgmentioning

confidence: 99%

“…The urea 63 is substituted at the ortho-position in high yield, 63,64 whereas the carbamate 65 is substituted substantially at the α-position. 63,[66][67][68][69] The amide 64 gives a mixture of the two substitution products, 64,65 but increasing the basicity of the lithiating agent by addition of TMEDA or t-BuOK shifts the selectivity to the α-substituted product. 65 These trends can be understood in terms of two properties of the carbonyl groups in the three DMGs, namely their ability to withdraw electron density from the α-attached nitrogen atom (carbamate > amide > urea) and the strength of their ability to complex an organolithium reagent (urea > amide > carbamate), which correlate with the carbonyl group stretching frequencies of such groups (carbamate > amide > urea).…”

Section: Effect Of the Dmgmentioning

confidence: 99%

Unravelling Factors Affecting Directed Lithiation of Acylaminoaromatics

2018

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Ureas, pivalamides, and carbamates are widely used as directing metalation groups (DMGs) due to their good directing ability, low cost, ease of access, and ease of removal. Lithiation of substituted benzenes having such directing metalation groups using various alkyllithiums in anhydrous solvent at low temperature provides the corresponding lithium intermediates, but lithiation may take place at various sites. Reactions of the lithium reagents obtained in situ with various electrophiles give the corresponding derivatives, typically substituted at the site(s) where initial lithiation occurred, often in high yields. However, it is often difficult to predict what reagents and/or conditions might be needed to give specific products or to draw general conclusions about the factors that influence the reactions, especially when the reagents, temperature, and solvents used in reported reactions are not directly comparable. In this review, therefore, we attempt to unravel the various factors that influence the lithiation of various simple aromatic compounds containing urea, pivalamide, and carbamate groups.1 Introduction2 Lithiation with DMG Attached Directly to the Phenyl Ring2.1 Influence of the DMG2.2 Influence of Substitution on the Phenyl Ring3 Lithiation with the DMG Separated by a CH2 Group from the Phenyl Ring3.1 Effect of the DMG3.2 Influence of Substitution on the Phenyl Ring4 Lithiation with the Phenyl Ring and DMG Separated by Two or More CH2 Groups4.1 Effect of the DMG and Its Distance from the Phenyl Group4.2 Effect of Substituents on the Phenyl Ring5 Conclusions

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Rapid access to N -Boc phenylglycine derivatives via benzylic lithiation reactions

Cited by 31 publications

References 38 publications

A Generic Approach for the Catalytic Reduction of Nitriles.

A Generic Approach for the Catalytic Reduction of Nitriles.

Synthesis of N-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation of N-Boc-α-aminosulfones

Unravelling Factors Affecting Directed Lithiation of Acylaminoaromatics

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Rapid access to N -Boc phenylglycine derivatives via benzylic lithiation reactions

Cited by 31 publications

References 38 publications

A Generic Approach for the Catalytic Reduction of Nitriles.

A Generic Approach for the Catalytic Reduction of Nitriles.

Synthesis of N-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation of N-Boc-α-aminosulfones

Unravelling Factors Affecting Directed Lithiation of Acylamino­aromatics

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Unravelling Factors Affecting Directed Lithiation of Acylaminoaromatics