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James E Thomson - One of the best experts on this subject based on the ideXlab platform.
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asymmetric syntheses of 2r 3s 3 hydroxyproline and 2s 3s 3 hydroxyproline
Organic Letters, 2018Co-Authors: Stephen G Davies, Ai M Fletcher, Sean M Linsdall, Paul M Roberts, James E ThomsonAbstract:Two synthetic routes have been developed for the asymmetric syntheses of (2R,3S)- and (2S,3S)-3-hydroxyproline. The key synthetic step in each of these strategies is the conversion of protected α,δ-dihydroxy-β-Amino Esters (either 2,3-anti- or 2,3-syn-configured) into β,δ-dihydroxy-α-Amino Esters (protected forms thereof), via the intermediacy of the corresponding aziridinium ions. The products of these stereospecific rearrangements were then cyclized and deprotected to afford (2R,3S)-3-hydroxyproline and (2S,3S)-3-hydroxyproline as single diastereoisomers (>99:1 dr) in >26% overall yield.
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trading n and o part 3 synthesis of 1 2 3 4 tetrahydroisoquinolines from α hydroxy β Amino Esters
Tetrahedron, 2016Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, Matthew S Kennedy, James E ThomsonAbstract:Abstract A range of enantiopure 1,2,3,4-tetrahydroisoquinolines have been prepared directly from α-hydroxy-β-Amino Esters. Activation of the α-hydroxy group upon treatment with Tf2O and 2,6-di-tert-butyl-4-methylpyridine promotes aziridinium formation, which is then followed by rupture of the C(3)–N bond and Friedel–Crafts alkylation-type cyclisation of an N-benzyl moiety onto the resultant benzylic carbenium ion. The nature of the N-protecting group was varied and it was found that superior yields were obtained for reactions employing two benzylic groups. In the cases where two different N-benzyl groups were used, the regioselectivity resulting from competitive cyclisation of either N-benzyl group was addressed by the introduction of a p-trifluoromethyl group on one of the N-benzyl moieties, which retarded the rate of cyclisation via this electron poor aryl ring. This methodology was employed in the asymmetric synthesis of a range of enantiopure 1,2,3,4-tetrahydroisoquinolines, which were isolated in good yields as single diastereoisomers.
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Asymmetric Synthesis of Substituted anti-β-Fluorophenylalanines
2015Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, James E ThomsonAbstract:A range of substituted anti-β-fluorophenylalanines was produced from the corresponding enantiopure α‑hydroxy-β-Amino Esters using a stereospecific XtalFluor-E promoted rearrangement procedure as the key step. The requisite substrates are readily produced via Aminohydroxylation of an α,β-unsaturated ester using our lithium amide conjugate addition methodology and, following rearrangement, deprotection of the resultant enantiopure β-fluoro-α-Amino Esters gives the corresponding enantiopure anti-β-fluorophenylalanines in good yield and high diastereoisomeric purity
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stereospecific cyclization strategies for α e dihydroxy β Amino Esters asymmetric syntheses of imino and Amino sugars
Journal of Organic Chemistry, 2014Co-Authors: Stephen G Davies, Paul M Roberts, Emma M Foster, James A Lee, James E ThomsonAbstract:A range of biologically significant imino and Amino sugars [1,4-dideoxy-1,4-imino-d-allitol, 3,6-dideoxy-3,6-imino-l-allonic acid, (3R,4S)-3,4-dihydroxy-l-proline, 1,5-anhydro-4-deoxy-4-Amino-d-glucitol, and 1,5-anhydro-4-deoxy-4-Amino-l-iditol] has been prepared via stereospecific cyclization of α,e-dihydroxy-β-Amino Esters. These substrates are readily prepared via conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to enantiopure α,β-unsaturated Esters (β-substituted with cis- and trans-dioxolane units) coupled with in situ enolate oxidation with camphorsulfonyloxaziridine (CSO). Activation of the e-hydroxyl group allowed cyclization to either the corresponding pyrrolidine or the tetrahydropyran scaffold, with the course of the cyclization process being dictated by the relative configuration of the dioxolane unit. When the α,e-dihydroxy-β-Amino ester bears a cis-dioxolane unit, cyclization occurs upon attack of the β-Amino substituent to give the corresponding pyrrolidine after in situ N...
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trading n and o part 2 exploiting aziridinium intermediates for the synthesis of β hydroxy α Amino acids
Tetrahedron, 2014Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, James E ThomsonAbstract:Abstract The β-hydroxy-α-Amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-Amino Esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding aziridinium ions. The starting anti-α-hydroxy-β-Amino Esters were prepared in >99:1 dr using our diastereoselective Aminohydroxylation procedure, whereby conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester is followed by oxidation of the resultant enolate with (−)-camphorsulfonyloxaziridine. Subsequent activation of the hydroxyl group within the anti-α-hydroxy-β-Amino Esters promoted aziridinium ion formation [which proceeds with inversion of configuration at C(2)], and regioselective ring-opening of the intermediate aziridinium ions with H2O [which proceeds with inversion of configuration at C(3)] gave the corresponding anti-β-hydroxy-α-Amino Esters as single diastereoisomers (>99:1 dr). Deprotection of these substrates via sequential hydrogenolysis and ester hydrolysis gave the corresponding β-hydroxy-α-Amino acids in good yield and high diastereoisomeric and enantiomeric purity.
Yian Shi - One of the best experts on this subject based on the ideXlab platform.
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organocatalytic synthesis of optically active β branched α Amino Esters via asymmetric biomimetic transamination
Organic and Biomolecular Chemistry, 2014Co-Authors: Ying Xie, Mao Liu, Yian Shi, Hongjie Pan, Hua TianAbstract:This paper describes an efficient asymmetric biomimetic transamination of α-keto Esters with a quinine-derived chiral base as the catalyst, giving a variety of β-branched α-Amino Esters in 50–96% yield and 87–95% ee.
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An Efficient Asymmetric Biomimetic Transamination of α-Keto Esters to Chiral α-Amino Esters
Organic letters, 2012Co-Authors: Xiao Xiao, Mao Liu, Chao Rong, Fazhen Xue, Ying Xie, Yian ShiAbstract:An efficient asymmetric biomimetic transamination of α-keto Esters with quinine derivatives as chiral bases was described. A wide variety of α-Amino Esters containing various functional groups can be synthesized in high yield and enantioselectivity.
Stephen G Davies - One of the best experts on this subject based on the ideXlab platform.
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asymmetric syntheses of 2r 3s 3 hydroxyproline and 2s 3s 3 hydroxyproline
Organic Letters, 2018Co-Authors: Stephen G Davies, Ai M Fletcher, Sean M Linsdall, Paul M Roberts, James E ThomsonAbstract:Two synthetic routes have been developed for the asymmetric syntheses of (2R,3S)- and (2S,3S)-3-hydroxyproline. The key synthetic step in each of these strategies is the conversion of protected α,δ-dihydroxy-β-Amino Esters (either 2,3-anti- or 2,3-syn-configured) into β,δ-dihydroxy-α-Amino Esters (protected forms thereof), via the intermediacy of the corresponding aziridinium ions. The products of these stereospecific rearrangements were then cyclized and deprotected to afford (2R,3S)-3-hydroxyproline and (2S,3S)-3-hydroxyproline as single diastereoisomers (>99:1 dr) in >26% overall yield.
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trading n and o part 3 synthesis of 1 2 3 4 tetrahydroisoquinolines from α hydroxy β Amino Esters
Tetrahedron, 2016Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, Matthew S Kennedy, James E ThomsonAbstract:Abstract A range of enantiopure 1,2,3,4-tetrahydroisoquinolines have been prepared directly from α-hydroxy-β-Amino Esters. Activation of the α-hydroxy group upon treatment with Tf2O and 2,6-di-tert-butyl-4-methylpyridine promotes aziridinium formation, which is then followed by rupture of the C(3)–N bond and Friedel–Crafts alkylation-type cyclisation of an N-benzyl moiety onto the resultant benzylic carbenium ion. The nature of the N-protecting group was varied and it was found that superior yields were obtained for reactions employing two benzylic groups. In the cases where two different N-benzyl groups were used, the regioselectivity resulting from competitive cyclisation of either N-benzyl group was addressed by the introduction of a p-trifluoromethyl group on one of the N-benzyl moieties, which retarded the rate of cyclisation via this electron poor aryl ring. This methodology was employed in the asymmetric synthesis of a range of enantiopure 1,2,3,4-tetrahydroisoquinolines, which were isolated in good yields as single diastereoisomers.
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Asymmetric Synthesis of Substituted anti-β-Fluorophenylalanines
2015Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, James E ThomsonAbstract:A range of substituted anti-β-fluorophenylalanines was produced from the corresponding enantiopure α‑hydroxy-β-Amino Esters using a stereospecific XtalFluor-E promoted rearrangement procedure as the key step. The requisite substrates are readily produced via Aminohydroxylation of an α,β-unsaturated ester using our lithium amide conjugate addition methodology and, following rearrangement, deprotection of the resultant enantiopure β-fluoro-α-Amino Esters gives the corresponding enantiopure anti-β-fluorophenylalanines in good yield and high diastereoisomeric purity
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stereospecific cyclization strategies for α e dihydroxy β Amino Esters asymmetric syntheses of imino and Amino sugars
Journal of Organic Chemistry, 2014Co-Authors: Stephen G Davies, Paul M Roberts, Emma M Foster, James A Lee, James E ThomsonAbstract:A range of biologically significant imino and Amino sugars [1,4-dideoxy-1,4-imino-d-allitol, 3,6-dideoxy-3,6-imino-l-allonic acid, (3R,4S)-3,4-dihydroxy-l-proline, 1,5-anhydro-4-deoxy-4-Amino-d-glucitol, and 1,5-anhydro-4-deoxy-4-Amino-l-iditol] has been prepared via stereospecific cyclization of α,e-dihydroxy-β-Amino Esters. These substrates are readily prepared via conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to enantiopure α,β-unsaturated Esters (β-substituted with cis- and trans-dioxolane units) coupled with in situ enolate oxidation with camphorsulfonyloxaziridine (CSO). Activation of the e-hydroxyl group allowed cyclization to either the corresponding pyrrolidine or the tetrahydropyran scaffold, with the course of the cyclization process being dictated by the relative configuration of the dioxolane unit. When the α,e-dihydroxy-β-Amino ester bears a cis-dioxolane unit, cyclization occurs upon attack of the β-Amino substituent to give the corresponding pyrrolidine after in situ N...
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trading n and o part 2 exploiting aziridinium intermediates for the synthesis of β hydroxy α Amino acids
Tetrahedron, 2014Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, James E ThomsonAbstract:Abstract The β-hydroxy-α-Amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-Amino Esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding aziridinium ions. The starting anti-α-hydroxy-β-Amino Esters were prepared in >99:1 dr using our diastereoselective Aminohydroxylation procedure, whereby conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester is followed by oxidation of the resultant enolate with (−)-camphorsulfonyloxaziridine. Subsequent activation of the hydroxyl group within the anti-α-hydroxy-β-Amino Esters promoted aziridinium ion formation [which proceeds with inversion of configuration at C(2)], and regioselective ring-opening of the intermediate aziridinium ions with H2O [which proceeds with inversion of configuration at C(3)] gave the corresponding anti-β-hydroxy-α-Amino Esters as single diastereoisomers (>99:1 dr). Deprotection of these substrates via sequential hydrogenolysis and ester hydrolysis gave the corresponding β-hydroxy-α-Amino acids in good yield and high diastereoisomeric and enantiomeric purity.
Paul M Roberts - One of the best experts on this subject based on the ideXlab platform.
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asymmetric syntheses of 2r 3s 3 hydroxyproline and 2s 3s 3 hydroxyproline
Organic Letters, 2018Co-Authors: Stephen G Davies, Ai M Fletcher, Sean M Linsdall, Paul M Roberts, James E ThomsonAbstract:Two synthetic routes have been developed for the asymmetric syntheses of (2R,3S)- and (2S,3S)-3-hydroxyproline. The key synthetic step in each of these strategies is the conversion of protected α,δ-dihydroxy-β-Amino Esters (either 2,3-anti- or 2,3-syn-configured) into β,δ-dihydroxy-α-Amino Esters (protected forms thereof), via the intermediacy of the corresponding aziridinium ions. The products of these stereospecific rearrangements were then cyclized and deprotected to afford (2R,3S)-3-hydroxyproline and (2S,3S)-3-hydroxyproline as single diastereoisomers (>99:1 dr) in >26% overall yield.
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trading n and o part 3 synthesis of 1 2 3 4 tetrahydroisoquinolines from α hydroxy β Amino Esters
Tetrahedron, 2016Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, Matthew S Kennedy, James E ThomsonAbstract:Abstract A range of enantiopure 1,2,3,4-tetrahydroisoquinolines have been prepared directly from α-hydroxy-β-Amino Esters. Activation of the α-hydroxy group upon treatment with Tf2O and 2,6-di-tert-butyl-4-methylpyridine promotes aziridinium formation, which is then followed by rupture of the C(3)–N bond and Friedel–Crafts alkylation-type cyclisation of an N-benzyl moiety onto the resultant benzylic carbenium ion. The nature of the N-protecting group was varied and it was found that superior yields were obtained for reactions employing two benzylic groups. In the cases where two different N-benzyl groups were used, the regioselectivity resulting from competitive cyclisation of either N-benzyl group was addressed by the introduction of a p-trifluoromethyl group on one of the N-benzyl moieties, which retarded the rate of cyclisation via this electron poor aryl ring. This methodology was employed in the asymmetric synthesis of a range of enantiopure 1,2,3,4-tetrahydroisoquinolines, which were isolated in good yields as single diastereoisomers.
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Asymmetric Synthesis of Substituted anti-β-Fluorophenylalanines
2015Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, James E ThomsonAbstract:A range of substituted anti-β-fluorophenylalanines was produced from the corresponding enantiopure α‑hydroxy-β-Amino Esters using a stereospecific XtalFluor-E promoted rearrangement procedure as the key step. The requisite substrates are readily produced via Aminohydroxylation of an α,β-unsaturated ester using our lithium amide conjugate addition methodology and, following rearrangement, deprotection of the resultant enantiopure β-fluoro-α-Amino Esters gives the corresponding enantiopure anti-β-fluorophenylalanines in good yield and high diastereoisomeric purity
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stereospecific cyclization strategies for α e dihydroxy β Amino Esters asymmetric syntheses of imino and Amino sugars
Journal of Organic Chemistry, 2014Co-Authors: Stephen G Davies, Paul M Roberts, Emma M Foster, James A Lee, James E ThomsonAbstract:A range of biologically significant imino and Amino sugars [1,4-dideoxy-1,4-imino-d-allitol, 3,6-dideoxy-3,6-imino-l-allonic acid, (3R,4S)-3,4-dihydroxy-l-proline, 1,5-anhydro-4-deoxy-4-Amino-d-glucitol, and 1,5-anhydro-4-deoxy-4-Amino-l-iditol] has been prepared via stereospecific cyclization of α,e-dihydroxy-β-Amino Esters. These substrates are readily prepared via conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to enantiopure α,β-unsaturated Esters (β-substituted with cis- and trans-dioxolane units) coupled with in situ enolate oxidation with camphorsulfonyloxaziridine (CSO). Activation of the e-hydroxyl group allowed cyclization to either the corresponding pyrrolidine or the tetrahydropyran scaffold, with the course of the cyclization process being dictated by the relative configuration of the dioxolane unit. When the α,e-dihydroxy-β-Amino ester bears a cis-dioxolane unit, cyclization occurs upon attack of the β-Amino substituent to give the corresponding pyrrolidine after in situ N...
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trading n and o part 2 exploiting aziridinium intermediates for the synthesis of β hydroxy α Amino acids
Tetrahedron, 2014Co-Authors: Stephen G Davies, Aileen B Frost, Ai M Fletcher, Paul M Roberts, James E ThomsonAbstract:Abstract The β-hydroxy-α-Amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-Amino Esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding aziridinium ions. The starting anti-α-hydroxy-β-Amino Esters were prepared in >99:1 dr using our diastereoselective Aminohydroxylation procedure, whereby conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester is followed by oxidation of the resultant enolate with (−)-camphorsulfonyloxaziridine. Subsequent activation of the hydroxyl group within the anti-α-hydroxy-β-Amino Esters promoted aziridinium ion formation [which proceeds with inversion of configuration at C(2)], and regioselective ring-opening of the intermediate aziridinium ions with H2O [which proceeds with inversion of configuration at C(3)] gave the corresponding anti-β-hydroxy-α-Amino Esters as single diastereoisomers (>99:1 dr). Deprotection of these substrates via sequential hydrogenolysis and ester hydrolysis gave the corresponding β-hydroxy-α-Amino acids in good yield and high diastereoisomeric and enantiomeric purity.
Frederic Lamaty - One of the best experts on this subject based on the ideXlab platform.
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solventless mechanosynthesis of n protected Amino Esters
ChemInform, 2014Co-Authors: Laure Konnert, Frederic Lamaty, Jean Martinez, Evelina ColacinoAbstract:Mechanochemical derivatizations of either N- or C-unprotected Amino acids are performed in a vibrational or planetary ball mill under neat conditions.
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Solventless mechanosynthesis of N-protected Amino Esters.
The Journal of organic chemistry, 2014Co-Authors: Laure Konnert, Frederic Lamaty, Jean Martinez, Evelina ColacinoAbstract:Mechanochemical derivatizations of N- or C-protected Amino acids were performed in a ball mill under solvent-free conditions. A vibrational ball mill was used for the preparation of N-protected α- and β-Amino Esters starting from the corresponding N-unmasked precursors via a carbamoylation reaction in the presence of di-tert-butyl dicarbonate (Boc2O), benzyl chloroformate (Z-Cl) or 9-fluorenylmethoxycarbonyl chloroformate (Fmoc-Cl). A planetary ball mill proved to be more suitable for the synthesis of Amino Esters from N-protected Amino acids via a one-pot activation/esterification reaction in the presence of various dialkyl dicarbonates or chloroformates. The spot-to-spot reactions were straightforward, leading to the final products in reduced reaction times with improved yields and simplified work-up procedures.
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Mechanochemical Preparation of Hydantoins from Amino Esters: Application to the Synthesis of the Antiepileptic Drug Phenytoin
2014Co-Authors: Laure Konnert, Benjamin reneaud, Jean-marc Campagne, Frederic Lamaty, Jean Martinez, Renata Marcia De Figueiredo, Evelina ColacinoAbstract:The eco-friendly preparation of 5- and 5,5-disubstituted hydantoins from various Amino ester hydrochlorides and potassium cyanate in a planetary ball-mill is described. The one-pot/two-step protocol consisted in the formation of ureido ester intermediates, followed by a base-catalyzed cyclization to hydantoins. This easy-handling mechanochemical methodology was applied to a large variety of α- and β-Amino Esters, in smooth conditions, leading to hydantoins in good yields and with no need of purification steps. As an example, the methodology was applied to the “green” synthesis of the antiepileptic drug Phenytoin, with no use of any harmful organic solvent
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solvent free synthesis of unsaturated Amino Esters in a ball mill
Tetrahedron Letters, 2010Co-Authors: Alice Baron, Jean Martinez, Frederic LamatyAbstract:Abstract The ball-milling technique was used under solvent-free conditions to perform a Horner–Wadsworth–Emmons reaction in the presence of a mild carbonate base. Starting from a phosphonate-substituted glycine, this method gave access to Boc-protected unsaturated Amino Esters in excellent yield and selectivity in many cases. The scope of the reaction was delineated.
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selective 3 2 huisgen cycloaddition synthesis of trans disubstituted triazolodiazepines from aza baylis hillman adducts
Journal of Organic Chemistry, 2009Co-Authors: Valerie Declerck, Jean Martinez, Loic Toupet, Frederic LamatyAbstract:The 1,3 dipolar cycloaddition of linear azido derived from protected s-Amino Esters proceeds via diastereoisomeric differentiation to provide trans-disubstituted triazolodiazepines in good yields.