Asymmetric Synthesis of δ‐Chloro‐β‐amino‐<i>N</i>‐sulfinyl Imidates as Versatile Chiral Building Blocks for the Synthesis of 2,3‐Disubstituted Piperidines

Semina, Elena; Colpaert, Filip; Hecke, Kristof Van; Kimpe, Norbert De; Mangelinckx, Sven

doi:10.1002/ejoc.201500466

Cited by 18 publications

(8 citation statements)

References 88 publications

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“…With two efficient methods for the synthesis of sulfonyl and sulfinyl imines from acetals, and being also interested in imidates, , we next considered applying similar conditions to the preparation of N -sulfonyl- and N -sulfinylimidates from orthoesters. N -Sulfonylimidates have mainly been used in diastereoselective α-alkylation reactions, ,, and can easily be converted into amides or esters, whereas N -sulfinylimidates have found applications in diastereoselective alkylations, Mannich-type condensations, conjugate additions, and diastereoselective aldol-type reactions . A few methods have been described for the preparation of such imidates, which suffer of long reaction time and tedious procedures.…”

Section: Resultsmentioning

confidence: 99%

Metal Free, Microwave Assisted Preparation of N-Sulfonyl and N-Sulfinyl Imines and Imidates

Verrier

Carret

Poisson

2018

ACS Sustainable Chem. Eng.

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Section: Resultsmentioning

confidence: 99%

Metal Free, Microwave Assisted Preparation of N-Sulfonyl and N-Sulfinyl Imines and Imidates

Verrier

Carret

Poisson

2018

ACS Sustainable Chem. Eng.

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“…The corresponding nucleophilic addition of enolizable N - t BS imines has met with limited success, in part because of a competing self-condensation reaction that occurs at the enolization step in the presence of bases . Replacing N - t BS imines with N ′- t BS amidines or N - t BS imidates can avoid this problem, allowing C–C bond formation in such reactions as alkylation, Mannich addition, and Michael addition (Scheme ). Aldolization is also feasible when TiCl 2 (O i Pr) 2 /Et 3 N is used because this species simultaneously promotes enolization and suppresses the reverse reaction of aldol condensation …”

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confidence: 99%

Diastereoselective Electrophilic α-Hydroxyamination of N-tert-Butanesulfinyl Imidates

Liu

et al. 2017

Org. Lett.

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“…To improve yield and diastereoselectivity, we focused on the replacement of the oxygen of the carbonyl group of mercaptoacetate with chiral tert -butanesulfinylamides . As chiral equivalents of esters or amides, N - t BS imidates/amidines have been used in diastereoselective α-functionalizations such as alkylation, hydroxylation, fluorination, sulfenylation, and nucleophilic addition to compounds bearing polarized π-bonds, such as aldehydes, imines, nitrosoarenes, N -aryl- N -diphenylphosphinyldiazenes, and 1,4-addition acceptors suggesting the possibility of diastereoselective synthesis of α-mercapto-β-amino acid derivatives via a Mannich-type reaction using α-sulfanyl N - t BS imidates and N -tosyl imines.…”

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confidence: 99%

Mannich-Type Reaction of α-Sulfanyl N-tert-Butanesulfinylimidates: Diastereoselective Access to α-Mercapto-β-amino Acid Derivatives

et al. 2021

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A series of α-mercapto-β-amino acid derivatives were synthesized diastereoselectively in good yields through the azaenolization of α-sulfanyl N-tert-butanesulfinylimidates, followed by their nucleophilic addition to N-tosyl imines via a Mannich-type reaction. The resulting derivatives bearing a β-sulfonylamino sulfide moiety participated in further inter-and intramolecular transformations involving episulfonium ion intermediates generated through neighboring-group participation.E nantioenriched α-mercapto-β-amino acid derivatives have been extensively studied due to their diverse biological activities. 1 For example, pseudotripeptides bearing an αmercapto-β-amino acid residue can efficiently inhibit aminopeptidase A, 2 tetanus neurotoxin, 3 and botulinum neurotoxin type B4. 4 Such derivatives can also be considered as bioisosteres of α-hydroxy-β-amino acid derivatives and are commonly used to elucidate structure−activity relationships. 5 Recently, several asymmetric catalytic methods have been developed for the enantioselective synthesis of α-mercapto-βamino acid analogues, such as chiral secondary amine-catalyzed aminosulfenylation of α,β-unsaturated aldehydes, 6 chiral picolinamide-catalyzed hydrosilylation−transacylation of αacylthio-β-enamino esters, 7 and reactions involving imine addition, which include the organocatalytic reaction between α-thio-acetaldehydes with imines, 8 the chiral bis-(imidazoline)−palladium-catalyzed reaction of α-(phenylthio)acetonitriles with imines, 9 and the reaction of α-diazo esters, thiols, and imines cocatalyzed by rhodium(II) and chiral phosphoric acid. 10 Methods using chiral starting materials have also been reported, such as ring opening of chiral oxazoline-5carboxylate using thiolacetic acid 11 and conjugate addition of homochiral lithium amides to cinnamate, followed by enolate trapping with electrophilic sulfur sources. 12 Among these strategies, Mannich-type reactions can produce two adjacent stereogenic centers through one-step C−C bond formation, which allows the selective introduction of αand βsubstituents using appropriate reaction partners. Chiral enolates and imines or their equivalents have been used in asymmetric Mannich-type reactions to prepare β-amino acid derivatives, 13 but few studies have reported the synthesis of αsulfanyl analogues. Here, we prepared chiral aza-enolates from α-sulfanyl N-tert-butanesulfinyl (N-tBS) imidates and then subjected them to nucleophilic addition to N-tosyl imines in order to generate α-mercapto-β-amino acid derivatives diastereoselectively (Scheme 1).

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Asymmetric Synthesis of δ‐Chloro‐β‐amino‐N‐sulfinyl Imidates as Versatile Chiral Building Blocks for the Synthesis of 2,3‐Disubstituted Piperidines

Cited by 18 publications

References 88 publications

Metal Free, Microwave Assisted Preparation of N-Sulfonyl and N-Sulfinyl Imines and Imidates

Metal Free, Microwave Assisted Preparation of N-Sulfonyl and N-Sulfinyl Imines and Imidates

Diastereoselective Electrophilic α-Hydroxyamination of N-tert-Butanesulfinyl Imidates

Mannich-Type Reaction of α-Sulfanyl N-tert-Butanesulfinylimidates: Diastereoselective Access to α-Mercapto-β-amino Acid Derivatives

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