Enantioselective Synthesis of α,β-Disubstituted-β-amino Acids

Sibi, Mukund P.; Narayanasamy, Prabagaran; Ghorpade, Sandeep R.; Jasperse, Craig P.

doi:10.1021/ja0372309

Cited by 121 publications

(46 citation statements)

References 18 publications

(10 reference statements)

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“…[a] Finally, the addition to tigloyl derivatives 14 [14] and 15 was studied. These reactions were extremely sluggish, furnishing low yields even with the most reactive 4-chloroaniline (entries 7 and 8).…”

Section: Synthesis Ofmentioning

confidence: 99%

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Elucidating the Mechanism of the Asymmetric Aza‐Michael Reaction

Phua

Mathew

White

et al. 2007

Chemistry A European J

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The mechanism of the palladium-catalysed asymmetric aza-Michael addition of aniline to alpha,beta-unsaturated N-imide was examined from several aspects using a combination of techniques, including X-ray crystallography, mass spectrometry, NMR, UV/Vis spectroscopy, and kinetic studies. The binding of aniline to the dicationic palladium(II) metal centre was found to occur in two consecutive steps: The binding of the first aniline is fast and reversible, whereas the binding of the second aniline is slower and irreversible. This occurs in competition with the binding of the N-imide, which forms a planar six-membered chelate ring with the metal centre; coordinating through the 1,3-dicarbonyl moiety. Isotopic labelling revealed that the addition of N-H occurs in a highly stereoselective manner, allowing the synthesis of optically active beta(2)- and beta(2,3)-amino acid derivatives. The stereochemistry of the addition is postulated to be syn. In situ kinetic studies provided evidence for product inhibition. The binding of the N-imide to the catalyst was found to be the rate-limiting step. Aniline was found to be an inhibitor of the pre-catalyst. The study culminated in the design of a new reaction protocol. By maintaining a low concentration of the aniline substrate during the course of the reaction, significant enhancement of yield and enantioselectivity can be achieved.

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Section: Synthesis Ofmentioning

confidence: 99%

“…The product was obtained as a white solid (1.64 g, 24 %). R f = 0.35 (Et 2 O) N-(2-Methylbut-2-enoyl)-benzamide (14): [14] The product was obtained as a white solid in 40 % yield. …”

Section: -[D]-n-(but-2-enoyl)-benzamide (2-[d]-4 A)mentioning

confidence: 99%

Elucidating the Mechanism of the Asymmetric Aza‐Michael Reaction

Phua

Mathew

White

et al. 2007

Chemistry A European J

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“…[14] Very recently, they extended the substrates to α,β-disubstituted imide-derived acceptors [Equation (2) in Scheme 5] and found that magnesium triflimide gave optimal enantioselectivity in the presence of the same bisoxazoline (up to 96 % ee). [15] Independently, Cardillo and coworkers discovered that low to moderate ee's (up to 29 % ee) could be obtained in the aza-Michael addition of BnONH 2 to doubly activated acceptors in the presence of a Cu II -box complex [Equation (1) in Scheme 6].…”

Section: Catalytic Asymmetric Aza-michael Reactions Of Hydroxylamine mentioning

confidence: 99%

A Catalytic Enantioselective Aza‐Michael Reaction: Novel Protocols for Asymmetric Synthesis of β‐Amino Carbonyl Compounds

Xia

2005

Eur J Org Chem

219

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β‐Amino carbonyl functionalities are ubiquitous motifs in natural and nonnatural products such as alkaloids and poly‐ketides. Among the reactions for the synthesis of β‐amino car‐bonyl compounds and β‐substituted β‐amino acids, aza‐Michael reactions using catalytic amounts of chiral Lewisacids might provide the best methods for the generation of optically active β‐amino carbonyl compounds. During the last five years, the asymmetric aza‐Michael reaction has emerged as a very powerful tool for the synthesis of chiral β‐amino carbonyl compounds, as will be discussed in this microreview. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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“…We have previously shown that imides of type 16 are quite reactive and have handles to provide rotamer control. 12 Competition between 3 and 16 shows that the imide 16 is twice as reactive than 3.…”

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confidence: 99%