Chiral β-amino sulfoxides. Synthesis, configurational assignment and conformational analysis based on X-ray, CD, 1H NMR and theoretical calculations

Lewanowicz, Aleksandra; Lipiński, Józef; Siedlecka, Renata; Skarżewski, Jacek; Baert, F.

doi:10.1016/s0040-4020(98)00317-2

Cited by 27 publications

(18 citation statements)

References 30 publications

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“…77 In a follow-up full paper, the authors outline additional noteworthy oxidations, offer thorough characterization of the sulfoxides, and mention the low diastereoselectivity of NaIO 4 and MCPBA oxidations. 81 In the Skarzewski papers, the authors prepare β-amino sulfoxides in good yields, with high dr's such as 85:15, 94:6, 77 98:2, and 92:8. 81 Some of the lower dr ratios were found at 53:47 or 64:36.…”

Section: ■ Discussionmentioning

confidence: 99%

“…26,28,36−38,42,50−53,66−79 Surprisingly, despite the presence of the stereogenic carbon, the diastereoselection of oxidation protocols has only rarely exceeded dr values of 90%. 77,80,81 In most cases, ratios range from 1:1 to 3:2, 26,28,36,37,42,51,[67][68][69][70][71]79 and on many occasions, diastereoselectivities are not even reported or acknowledged. 38,52,53,66,72−76 In the few instances when an asymmetric oxidizing agent was employed to complement the stereogenic carbon in the substrate, selected de values reach 95% but only for particular substrates and conditions.…”

Section: ■ Introductionmentioning

confidence: 99%

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Sulfenate Substitution as a Complement and Alternative to Sulfoxidation in the Diastereoselective Preparation of Chiral β-Substituted β-Amino Sulfoxides

Söderman

Schwan

2013

J. Org. Chem.

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Building from a previous communication, the reaction of sulfenate anions with chiral N-Boc-protected β-substituted β-amino iodides was evaluated as a conceptually different synthetic approach to chiral β-substituted β-amino sulfoxides. Using arenesulfenates, yields typically ranged from 71% to 92%, and dr's were often near 9:1. Alkanesulfenates proved less reactive, delivering lower yields and dr's. 1-Alkenesulfenates demonstrated high reactivity, returning chemical yields of 60-86% and dr's often close to 9:1 and as high as 95:5. (S)-β-Amino iodide electrophiles yielded (R(S),S(C))-β-amino sulfoxides, whereas (R)-amino iodides afford (S(S),R(C))-β-amino sulfoxides. The absolute configuration of the products makes the sulfenate protocol complementary to other existing preparations, including the commonly employed sulfoxidation of β-amino sulfides. The reactivity of N-Boc-protected 2-benzyl-2-aminoethyl iodide was found to be superior to the less sterically encumbered n-butyl iodide. A transition state model is proposed to account for the stereochemistry of the products and also for the high reactivity of the electrophile. Overall, the chemistry represents a new means of introducing sulfur stereogenicity in a molecule.

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Section: ■ Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Sulfenate Substitution as a Complement and Alternative to Sulfoxidation in the Diastereoselective Preparation of Chiral β-Substituted β-Amino Sulfoxides

Söderman

Schwan

2013

J. Org. Chem.

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“…Scheme 4 Diastereomers 12-(l) and 12-(u) were separated by HPLC and their configurations were identified by comparison of the 1 H NMR spectra with similar compounds reported in the literature, and by theoretical calculations. [16,23] The 1 H NMR spectra of each diastereomer shows that the difference in coupling constants for H a and H b with H x in one spectrum is 6 Hz, while in the other it is much less (1.4 Hz). As the differences between the 1 H NMR spectra of the two diastereomers can be described by the molecular geometry of the most stable conformer(s), we have calculated the ground-state geometry for each diastereomer using the semi-empirical MNDO method and two angles H x -C-C-S (α) and C-C-S-O (β).…”

Section: Scheme 2 Schemementioning

confidence: 99%

“…As the differences between the 1 H NMR spectra of the two diastereomers can be described by the molecular geometry of the most stable conformer(s), we have calculated the ground-state geometry for each diastereomer using the semi-empirical MNDO method and two angles H x -C-C-S (α) and C-C-S-O (β). [23,24] These calculations show that the diastereomer (l) has two most-stable conformers, while diastereomer (u) has only one most-stable conformer. The most stable (l) and (u) conformers of compound 12 are shown in Figure 1.…”

Section: Scheme 2 Schemementioning

confidence: 99%

The LiClO4-Mediated Synthesis of β-(Dialkylamino) Sulfoxides and β-(Dialkylamino) Sulfones by Addition of α-Lithiated Salts of Sulfoxides and Sulfones to Aldehydes and (Trimethylsilyl)dialkylamines

Naimi‐Jamal¹,

Ipaktschi²,

Saidi³

2000

Eur. J. Org. Chem.

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The LiClO4‐mediated one‐pot reaction of aldehydes with (trimethylsilyl)dialkyl amines and the lithium salt of sulfoxides or sulfones, affords the corresponding β‐(dialkylamino) sulfoxides and β‐(dialkylamino) sulfones in high yields. The aminosulfoxidation reaction of aliphatic or aromatic aldehydes lacks diastereoselectivity, but the diastereomeric sulfoxides can be separated by HPLC or column chromatography for further use.

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“…Protection of (R)-5 with (Boc) 2 O provided N-Boc derivative (R)-6 in 73% yield according to the known procedure. 17 The second step of our sequence consisted in coupling the imide 7 with N-Boc-(R)-phenylglycinol (6). The Mitsunobu reaction was implemented with DIAD instead of DEAD usually employed as coupling reagent by applying conditions of Martinez et al (imide 7, DIAD, Ph 3 P, THF, 0°C).…”

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confidence: 99%

Acid-Promoted Aza-Cyclization versus π-Cyclization of N-Acyliminium Species into Fused Pyrrolo[1,2-a]imidazolones and Pyrrolo[2,1-a]isoquinolinones

Fleury¹,

Netchitaïlo²,

Daı̈ch³

2011

Synlett

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A new approach for the synthesis of fused imidazolones and isoquinolinones is presented. The key step of this sequence was the interception of an N-acyliminium species with nitrogen or p-aromatic nucleophiles under kinetic vs. thermodynamic control. In addition, in the presence of two p-aromatic nucleophiles, only the six-membered ring closure into pyrroloisoquinolinones occurred.N-Acyliminium species are intermediates which are widely used in modern organic synthesis. Their importance is underlined by numerous reviews of their generation and use for the elaboration of natural and unnatural aza-heterocyclic systems with therapeutic interest. 1 If the formation of the C-C bonds by this protocol in inter-and intramolecular fashion is widely applied by the scientific community, the one which consists in the formation of the C-X linkage with X as a heteroatom (X = O, S, Se, and N) appears to be a new field of application of this chemistry. 2,3We have described earlier the potential for these species to intercept intramolecularly nitrogen nucleophiles in acidic media. 2 In particular, their presence with both carbon-and nitrogen-tethered nucleophiles showed the reaction operability under kinetic vs. thermodynamic control (Scheme 1). This resulted in the formation of C-N bond (1, reversible) or C-C bond (2, irreversible) depending on the reaction conditions. 3 Similar processes in oxygen series are relatively well documented to provide, in particular, asymmetric macrocyclic N,O-acetals 4 and alkaloids. 5In both cases, Brønsted and Lewis acids were used as promoters.Moreover, cationic cyclization using a nitrogen atom as internal nucleophile was first mentioned during the synthesis of 9a-phenyltetrahydroisoindolo[2,1-a]quinazoline-5,11-dione 6a and ten years later for the production of diethyl tetrahydrodioxolo[4,5-g]pyrrolo[2,1-b]quinazoline-8,8-dicarboxylate. 6b Its power was also illustrated in the total synthesis of (±)-and (-)-physostigmine, 7 (±)-glochidine, and (±)-glochidicine, 8 imidazoloindoline alkaloids, 9a oroidin-derived alkaloids, 9b and more recently, the bioactive enantiopure (-)-decarbamoyloxy-saxitoxin. 10 Reports on this process concern also its use to access aldose reductase inhibitors, 11 in parallel synthesis of Δ 2 -2-oxopiperazines, 12 in asymmetric synthesis of Reissert compounds, 13 in synthesis of lactam-based peptidomimetics, 14 and in sterically hindered N-substituted and fused g-lactams. 15To the best of our knowledge, the use of the present application in both intramolecular and diastereoselective Nacyliminium-mediated cyclization represents a novel illustration of this chemistry (Scheme 2). This can result in the formation of a central five-membered ring of N,N-acetal 3 by nitrogen atom attack of the cation II (path a). However, when the aromatic system at the nitrogen a-position of II is sufficiently activated, a six-membered ring of fused isoquinoline 4 (path b) can be obtained. The cores of these tricyclic systems ars often encountered in natural products and biologically active compo...

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Chiral β-amino sulfoxides. Synthesis, configurational assignment and conformational analysis based on X-ray, CD, 1H NMR and theoretical calculations

Cited by 27 publications

References 30 publications

Sulfenate Substitution as a Complement and Alternative to Sulfoxidation in the Diastereoselective Preparation of Chiral β-Substituted β-Amino Sulfoxides

Sulfenate Substitution as a Complement and Alternative to Sulfoxidation in the Diastereoselective Preparation of Chiral β-Substituted β-Amino Sulfoxides

The LiClO4-Mediated Synthesis of β-(Dialkylamino) Sulfoxides and β-(Dialkylamino) Sulfones by Addition of α-Lithiated Salts of Sulfoxides and Sulfones to Aldehydes and (Trimethylsilyl)dialkylamines

Acid-Promoted Aza-Cyclization versus π-Cyclization of N-Acyliminium Species into Fused Pyrrolo[1,2-a]imidazolones and Pyrrolo[2,1-a]isoquinolinones

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