Acyl vs Sulfonyl Transfer in <i>N</i>-Acyl β-Sultams and 3-Oxo-β-sultams

Ahmed, Naveed; Tsang, Wing Y.; Page, Michael I.

doi:10.1021/ol0361305

Cited by 18 publications

(27 citation statements)

References 13 publications

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“…They show enormous rate enhancements over analogous reactions of sulfonamides [2]. They are potential sulfonylating agents of a variety of nucleophiles [3]. β-Sultams also have the potential to act as peptide mimics and as transition state analogues of the tetrahedral intermediates formed in many acyl transfer reactions [4].…”

Section: Introductionmentioning

confidence: 99%

“…β-Sultams also have the potential to act as peptide mimics and as transition state analogues of the tetrahedral intermediates formed in many acyl transfer reactions [4]. The mechanism of its action has been studied with experimental [2][3][4][5][6][7][8] and theoretical [9][10][11] methods.…”

Section: Introductionmentioning

confidence: 99%

“…The hydrolysis of this compound occurs with S N and C N fission but S N bond fission is preferential. That is to say, 3-oxo-β-sultam appears to inactivate elastase and possibly class C β-lactamase by acylation rather than sulfonylation [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Theoretical Study for Alcoholysis of N-Benzyl 3-Oxo-?-Sultam

Feng

et al. 2005

Struct Chem

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The alcoholysis mechanisms of N-benzyl 3-oxo-β-sultam are investigated at B3LYP/6-31G * level. Different possible mechanistic pathways of the reaction are proposed. The results show that the cleavage of S N bond producing P1 has a little lower energy barrier than does C N bond producing P2. The inclusion of solvent effects by a polarizable continuum model (PCM) does not change the conclusions based on the gas-phase study.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Theoretical Study for Alcoholysis of N-Benzyl 3-Oxo-?-Sultam

Feng

et al. 2005

Struct Chem

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“…By contrast, the alkaline hydrolysis of N-benzoyl -sultam (8) occurs exclusively by S-N fission as a result of attack on sulfur and displacement of the carboxamide, and occurs 10 4 faster than an analogous acyclic N-acylsulfonamide occurring by C-N fission. 16 The incorporation of the acyl centre within the fourmembered ring gives a structure (9) that is both asultam and a -lactam. 16 These 3-oxo -sultams undergo hydrolysis with preferential attack on the sulfonyl centre, leading to S-N fission.…”

Section: Hydrolysis Of B-sultamsmentioning

confidence: 99%

“…16 The incorporation of the acyl centre within the fourmembered ring gives a structure (9) that is both asultam and a -lactam. 16 These 3-oxo -sultams undergo hydrolysis with preferential attack on the sulfonyl centre, leading to S-N fission. Despite the enormous strain in 3-oxo -sultams, structure (9) is only 10-fold more reactive towards alkaline hydrolysis than the -sultam with an exocyclic acyl centre.…”

Section: Hydrolysis Of B-sultamsmentioning

confidence: 99%

Comparison of the mechanisms of reactions of β‐lactams and β‐sultams, including their reactions with some serine enzymes

Page

Tsang

Ahmed

2006

J of Physical Organic Chem

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The strain energy of the four-membered ring of -lactams is not released in the transition state to lower the activation energy of reactions involving ring-opening. The alkaline hydrolysis of N-aroyl -lactams occurs with competitive exo-and endocyclic C-N ring fission, the ratio of which varies with the aryl substituent. -Sultams are four-membered cyclic sulfonamides and are about 10 3 fold more reactive than analogous -lactams. Nucleophiles usually attack N-acylsulfonamides at the carbonyl centre resulting in C-N bond fission, but the hydrolysis of N-acyl -sultams occurs with S-N fission and opening of the four-membered ring. The 3-oxo--sultams are a unique combination of both -lactams and -sultams and therefore are susceptible to nucleophilic attack at either the acyl or the sulfonyl centre, but they hydrolyse with exclusive S-N bond fission. -Sultams are novel inhibitors of the serine enzymes elastase, transpeptidase and -lactamase due to sulfonylation of the active-site serine residue. Structureactivity relationships are used to identify differences in transition-state structures between -sultams as inhibitors and -lactams as substrates.

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Hydrogenation of N‐Acylcarbamates and N‐Acylsulfonamides Catalyzed by a Bifunctional [Cp*Ru(PN)] Complex

et al. 2009

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The development of well-designed molecular catalysts for the hydrogenation of polar organic functionalities continues to be an important challenge, because it would provide a solution to reducing the energy required and waste generated for such a reactions. It would also provide direct access to stereochemically well-defined molecules through a structural modification of the catalyst molecule.[1] The difficulty with this issue is the discovery of an appropriate catalyst which can generate a more hydridic species from molecular dihydrogen (H 2 ) with concomitant release of a more protic product by a formal heterolytic H 2 cleavage. Over a decade ago, an intriguing clue was offered by a Noyoris bifunctional catalyst, consisting of [RuCl 2 (diphosphane)(diamine)] and a base, for the hydrogenation of ketones, which promotes this energetically disfavored process with an aid of alcoholic solvents. [2,3] We also successfully developed new bifunctional catalyst systems comprised of [Cp*RuCl{L(CH 2 ) 2 NH 2 -k 2 -L,N}] complexes and a base for the highly efficient hydrogenation of polar organic functionalities (Cp* = h 5 -C 5 (CH 3 ) 5 ; L = (CH 3 ) 2 N, or (C 6 H 5 ) 2 P).[4] The nucleophilicity of the RuH moiety as well as the electrophilicity of the NH moiety in the catalytically active [Cp*RuH{L(CH 2 ) 2 NH 2 -k 2 -L,N}] complexes are suitably controlled by the electronic nature of L in the ligand (Scheme 1).For example, both [Cp*Ru(NN)] (N = tertiary amine) and [Cp*Ru(PN)] (P = tertiary phosphane) catalysts are capable of heterolytic H À H bond cleavage, wherein the increased p-accepting property of the tertiary phosphane enhances the Brønsted acidity of the ligated NH group to facilitate the activation of polar functional groups. Accordingly, [Cp*Ru(NN)] favorably promotes the hydrogenation of ketones, [4a] whereas [Cp*Ru(PN)] effects the hydrogenation of epoxides [4b] and imides [4c] as well as ketones. This successful expansion of the Ru/NH bifunctionality [5] has led us to additionally examine the catalytic performance of [Cp*Ru(PN)] in the hydrogenation of polar organic functionalities and we found the unprecedented hydrogenation of N-acylcarbamates and N-acylsulfonamides. Herein, we disclose the details of the reactions and their synthetic applications.Initial experiments focused on the effect of alcoholic solvents upon the chemoselectivity in the hydrogenation of N-Boc-pyrrolidinone (2 a; Boc = CO 2 tBu) as a model substrate. The reaction was carried out at 80 8C under 3 MPa of H 2 in an alcoholic solvent containing 2 a, [Cp*RuCl{(C 6 H 5 ) 2 P-(CH 2 ) 2 NH 2 -k 2 -P,N}] (1), and KOtBu (2 a/Ru/KOtBu = 100:1:1, [2 a] = 0.2 m). Substrate 2 a was smoothly consumed in a variety of alcoholic solvents, but the reaction course was delicately influenced by the sterics of the alcohol employed. In fact, the use of methanol or 2-propanol significantly caused alcoholysis in addition to the hydrogenation of 2 a to result in the formation of a mixture of BocNH(CH 2 ) 4 OH (2 ax) and BocNH(CH 2 ) 3 CO 2 R (2 ay: R = CH 3 ...

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Acyl vs Sulfonyl Transfer in N-Acyl β-Sultams and 3-Oxo-β-sultams

Cited by 18 publications

References 13 publications

Theoretical Study for Alcoholysis of N-Benzyl 3-Oxo-?-Sultam

Theoretical Study for Alcoholysis of N-Benzyl 3-Oxo-?-Sultam

Comparison of the mechanisms of reactions of β‐lactams and β‐sultams, including their reactions with some serine enzymes

Hydrogenation of N‐Acylcarbamates and N‐Acylsulfonamides Catalyzed by a Bifunctional [Cp*Ru(PN)] Complex

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