Electrophile-Directed Diastereoselective Alkylation of Prochiral Enediolates

Marsden, Stephen P.; Newton, Rebecca

doi:10.1021/ja073624e

Cited by 21 publications

(5 citation statements)

References 14 publications

(15 reference statements)

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“…A particularly selective alkylation occurs between the ketoamide 75 and the secondary iodide 77 . In this case the unusual dienolate 76 , formed by double deprotonation, engages in chelation between the enolate and the PMB ether, localizing the displacement within a 6‐membered transition structure ( 78 → 79 , Scheme ).…”

Section: Alkylations With Secondary Electrophilesmentioning

confidence: 99%

“…Chelation is critical for diastereoselective alkylations of the chiral iodide 154 with the prochiral dienediolate derived from 153 (Scheme ) . Varying the substituents R 1 on the dienediolate did not significantly alter the ratio of the diastereomers.…”

Section: Alkylations With Primary Electrophilesmentioning

confidence: 99%

“…A less sterically demanding orientation positions A particularly selective alkylation occurs between the ketoamide 75 and the secondary iodide 77. [45] In this case the unusual dienolate 76, formed by double deprotonation, engages in chelation between the enolate and the PMB ether, localizing the displacement within a 6-membered transition structure (78 → 79, Scheme 17). A campaign to prepare unnatural amino acids, such as (2S, 3R)-3-methyl glutamic acid present in nonribosomal lipo peptide antiobiotics, provided key insight into the alkylations of benzophenone imines with 2-sulfonyloxyalkanes (Scheme 18).…”

Section: Secondary Aliphatic Electrophilesmentioning

confidence: 99%

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Diastereoselective Electrophile‐Directed Alkylations

2019

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Electrophile‐directed alkylations in which a chiral, sp3‐hybridized electrophile, dictates the facial attack on a prochiral nucleophile, provides a powerful method of asymmetric induction. The strategy is inherently efficient because the asymmetry of an sp3‐hybridized electrophile is propagated to install two contiguous chiral centers, the first through an SN2 displacement and the second through preferential facial recognition. The two primary modes of topological matching are through steric approach control and chelation between the electrophile and nucleophile. Electrophiles capable of chelation generally induce higher diastereoselectivity for secondary and primary electrophiles. Key parameters that influence the stereoselectivity are those expected for enolate/anion alkylations: solvent, cation, complexing agents. A generalized enolate‐electrophile alkylation model is used to provide an evaluative framework for collecting related alkylations with the aim of providing insight into the origin of the electrophile‐directed diastereoselectivity as a powerful synthetic strategy.

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Section: Alkylations With Secondary Electrophilesmentioning

confidence: 99%

Section: Alkylations With Primary Electrophilesmentioning

confidence: 99%

Section: Secondary Aliphatic Electrophilesmentioning

confidence: 99%

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Diastereoselective Electrophile‐Directed Alkylations

2019

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“…Using achiral phase-transfer catalyst TBAB, substrate control from (S)-alanine-derived sulfamidate electrophile (S)-1 f was found to be highly nucleophile dependent, [17,18] varying from poor with lactone uously assigned by single crystal X-ray diffraction (see the Supporting Information for details). Using alanine as a convenient source of chirality, both enantiomers of sulfamidate 1 f were synthesized in the hope of observing "matched" and "mismatched" combinations of substrate and catalyst control.…”

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confidence: 99%

Catalytic Enantio‐ and Diastereoselective Alkylations with Cyclic Sulfamidates

et al. 2010

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The enantioselective construction of derivatives of g-amino butyric acid and d-amino pentanoic acid from simple starting materials using asymmetric catalysis provides convenient access to a range of structurally diverse natural products, pharmaceutical compounds, and potential building blocks for g-peptides and foldamer chemistry.[1] Several natural products containing the aminoethylene and aminopropylene scaffolds attached to a quaternary stereocenter have been isolated. Developments in the field of enantioselective Michael additions of carbonyl compounds to nitroolefins and acrylonitriles have been significant, with highly enantioselective examples reported in both cases. [2,3] We recognized that structures containing aminoethylene or aminopropylene moieties could be accessed rapidly and stereoselectively if suitable two-carbon or three-carbon nitrogen-containing electrophiles could be utilized. To this end, we recently described both the base-catalyzed, [4a] and the phasetransfer catalyzed enantio-and diastereoselective [4b] ringopening reactions of nitrogen-protected aziridines as a method for the direct construction of g-amino butyric acid derivatives. During the course of that study, we found that sulfonyl protection of the nitrogen atom was necessary to achieve acceptable levels of reactivity. Although the sulfonyl group could be cleaved under mild conditions in some cases, we believed that a method which encompassed a wider range of nitrogen-protecting groups would be more desirable. Furthermore, access to the aminopropylene unit (CH 2 CH 2 CH 2 NHP) remained elusive. Anticipating that azetidines would lack the required reactivity to be used as threecarbon electrophiles, [5] we considered cyclic sulfamidates as potential two-or three-carbon electrophile candidates. [6,7] Seminal work by Lubell and Wei [8] and extensive studies by Gallagher and co-workers [9,10] have found that five-membered and six-membered cyclic sulfamidates are useful precursors for the synthesis of pyrrolidine and piperidinone alkaloids. In those studies, methylene carbon acids were typically used as the nucleophile, with chiral enantiopure electrophiles. To the best of our knowledge, there have been no reports of a catalytic enantioselective nucleophilic ring-opening of cyclic sulfamidates with carbon-centered nucleophiles, despite the synthetic advantages of such an approach. We reasoned that a base-catalyzed reaction would be challenging, owing to the low basicity of sulfamic acid salts that can be formed from the ring opening of cyclic sulfamidates. Accordingly, we believed that an enantioselective ring-opening of cyclic sulfamidates could be realized using asymmetric phase-transfer catalysis with a stoichiometric base. [11,12] Attracted by the simplicity of the approach, and the synthetic potential of the methodology, we began our investigations. Herein, we report our findings into the direct enantioselective catalytic alkylation reaction of methine pro-nucleophiles with N-protected five-membered and six-membered cyclic sulfami...

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“…To date, however, there has been only a single example of the arylation of an alkoxy-substituted enolate, specifically, the synthesis of a spirocyclic oxindole by arylation of a 2-carboxytetrahydrofuran derivative . Given our interest in the construction of quaternary centers by functionalization of oxygen-substituted enolates, we wished to investigate the extension of enolate arylation chemistry to the synthesis of the valuable 3-alkoxy-3-aryloxindoles. Provided that the presence of the aryl substituent did not detrimentally affect the arylation process (for example by competing direct arylation), this would be an attractive convergent route to the target molecules, given the ready commercial availability of both substituted mandelic acid derivatives and o -haloanilines as building blocks.…”

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confidence: 99%