Improved Process for Preparation of <i>tert</i>-Butanesulfinyl Ketimines of Hindered Ketones under Nitrogen Flow

Tabet, Samuel; Rodeville, Nicolas; Boiteau, Jean‐Guy; Cardinaud, Isabelle

doi:10.1021/acs.oprd.6b00188

Cited by 8 publications

(7 citation statements)

References 19 publications

(30 reference statements)

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“…No significant difference was observed when the reaction was run neat or with an organic solvent under nitrogen flux or vacuum (regular refill of organic solvent was required to keep a constant volume). These conditions proved robust and scalable and were found to be applicable to a wide variety of substrates (especially for sterically hindered ketones), allowing a significant yield improvement under milder conditions by comparison with standard literature procedures …”

Section: Resultsmentioning

confidence: 99%

“…These conditions proved robust and scalable and were found to be applicable to a wide variety of substrates (especially for sterically hindered ketones), allowing a significant yield improvement under milder conditions by comparison with standard literature procedures. 15 Subsequent sulfinimine reduction could be performed with various reducing agents (NaBH 4 , BH 3 -THF, LiBH(Et) 3 , 9-Scheme 6. 3rd Generation Diastereoselective Route toward 2•HCl BBN...).…”

Section: ■ Introductionmentioning

confidence: 99%

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Early Development Scale-Up of a Novel CXCR Antagonist: Focus on Racemic and Stereoselective Routes of a Key Intermediate

Tabet

Rodeville

Mathieu

et al. 2017

Org. Process Res. Dev.

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Efforts toward a convenient and scalable process for the synthesis of a novel CXCR antagonist 1 are described, with a specific focus on a chiral key intermediate. Two generations of a racemic route have been developed for short-term deliveries, and a stereoselective process has been devised for longer term plans. Key steps involved an enzymatic resolution of racemic tetrahydrothiophene-2-carboxylic acid to install the (2R) stereocenter, the mild and efficient preparation of a sterically hindered sulfinimine under a nitrogen flow, and its stereoselective reduction to set up the (1S) amine stereocenter. The process has been scaled-up to multikilogram scale for the racemic approach, and the stereoselective route was demonstrated on multigram scale.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Early Development Scale-Up of a Novel CXCR Antagonist: Focus on Racemic and Stereoselective Routes of a Key Intermediate

Tabet

Rodeville

Mathieu

et al. 2017

Org. Process Res. Dev.

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“…For this, we chose iSnAP reagent B, prepared via a straightforward route, to test the second SnAP reaction. Despite the presence of the tertiary amine, ketimine formation assisted by Ti(OiPr) 4 proceeded smoothly under vacuum, 24 as did the cyclization with Cu(OTf) 2 to give two separable diastereomers in approximately 2:1 ratio, in 50% isolated yield. The structure of one of the diastereomers, Cbzpip-A(Me)-β-B(H)-ketal, was confirmed by X-ray diffraction of a single crystal.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Iterative Assembly of Polycyclic Saturated Heterocycles from Monomeric Building Blocks

2019

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Polycyclic saturated heterocycles with predictable shapes and structures are assembled by iterative couplings of bifunctional stannyl amine protocol (SnAP) reagents and a single morpholine-forming assembly reaction. Combinations of just a few monomers enable the programmable construction of rotationally restricted, nonplanar heterocyclic arrays with discrete sizes and molecular shapes. The three-dimensional structures of these constrained scaffolds can be quickly and reliably predicted by DFT calculations and the target structures immediately decompiled into the constituent building blocks and assembly sequences. As a demonstration, in silico combinations of the building blocks predict saturated heptacyclic structures with elementary shapes including helices, S-turns and U-turns, which are synthesized in 5–6 steps from the monomers using just three chemical reactions.

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“…Ketimines were also synthesized with Ti(OEt) 4 , under microwave irradiation in a solvent-free system [20]. In hindered ketones, Ti(OiPr) 4 or Ti(OEt) 4 using vacuum or under a nitrogen flow were effective to tert-butanesulfinyl ketimine condensation (Scheme 2) [21].…”

Section: Synthesis Of Tert-butane N-sulfinyl Iminesmentioning

confidence: 99%

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

Mendes¹,

Costa²,

Yus³

et al. 2021

Beilstein J. Org. Chem.

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The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.

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Improved Process for Preparation of tert-Butanesulfinyl Ketimines of Hindered Ketones under Nitrogen Flow

Cited by 8 publications

References 19 publications

Early Development Scale-Up of a Novel CXCR Antagonist: Focus on Racemic and Stereoselective Routes of a Key Intermediate

Early Development Scale-Up of a Novel CXCR Antagonist: Focus on Racemic and Stereoselective Routes of a Key Intermediate

Iterative Assembly of Polycyclic Saturated Heterocycles from Monomeric Building Blocks

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

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