<i>N-tert</i>-Butanesulfinyl Imines:  Versatile Intermediates for the Asymmetric Synthesis of Amines

Ellman, Jonathan A.; Owens, Timothy D.; Tang, Tony P.

doi:10.1021/ar020066u

Cited by 799 publications

(293 citation statements)

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“…Union of 4 and 5 via Suzuki reaction and subsequent acetate deprotection afforded primary alcohol 6. Oxidation and imine formation with (S)-tert-butyl sulfinamide 29 formed sulfinyl imine 7. The addition of the Reformatsky enolate of tert-butyl acetate to imine 7 afforded sulfinamine 8 and established the requisite stereocenter, albeit with modest diastereoselectivity (d.r.…”

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confidence: 99%

Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors

Gehling

Hewitt

Vaswani

et al. 2013

ACS Med. Chem. Lett.

100

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confidence: 99%

Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors

Gehling

Hewitt

Vaswani

et al. 2013

ACS Med. Chem. Lett.

100

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“…Indeed, the pioneering works of Davis and Ellman on the synthesis and reactivity of N-sulfinyl imines have given the synthetic community a readily available and robust precursor of optically active amine compounds. [8][9][10][11][12][13][14][15][16] Due to this rarity of radical species-mediated methods as well as our ongoing interest in radical reactions, [17][18][19] we sought to improve the efficiency and substrate scope of our initial report on radical addition of ethers and acetals to enantiopure N-p-toluenesulfinyl aldimines. 20) In this previous report, an in-house dimethylzinc-air radical initiator was used to generate carbon-centered a-alkoxyalkyl radicals from ethers and acetals.…”

Section: Notesmentioning

confidence: 99%

Stereoselective Radical Addition of an Acetal to Sterically Tuned Enantiomerically Pure N-Sulfinyl Imines

Akindele

Yamada

Sejima

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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NotesGiven the ubiquitous nature of the C-N stereogenic center, efficient synthetic methods continue to be developed for its installation in both simple and complex chemical structures.1-3) These methods could be broadly classified into reactions mediated by ionic or radical species. Majority of these methods are mediated by ionic species, requiring highly basic reagents which limit the substrate scope of these approaches, albeit the products are obtained in high yield and enantioselectivity. On the other hand, methods involving radical species 4,5) are relatively under explored despite the potential of this approach to deliver much more structurally varied products using milder reagents.To date, the lack of a catalytic asymmetric radical addition method to N-sulfonyl imines 6,7) has made the use of chiral Nsulfinyl imines as radical acceptors, for creating predictable stereodefined C-N stereogenic centers in sulfonamides, an appealing alternative synthetic strategy. Indeed, the pioneering works of Davis and Ellman on the synthesis and reactivity of N-sulfinyl imines have given the synthetic community a readily available and robust precursor of optically active amine compounds. [8][9][10][11][12][13][14][15][16] Due to this rarity of radical species-mediated methods as well as our ongoing interest in radical reactions, [17][18][19] we sought to improve the efficiency and substrate scope of our initial report on radical addition of ethers and acetals to enantiopure N-p-toluenesulfinyl aldimines. 20) In this previous report, an in-house dimethylzinc-air radical initiator was used to generate carbon-centered a-alkoxyalkyl radicals from ethers and acetals. Subsequent nucleophilic addition of the radicals to the enantiopure N-sulfinyl imines followed by oxidation afforded the sulfonamide adducts in enantiomerically enriched forms. It is noteworthy that boron trifluoride diethyl etherate was essential for faster reaction rate while a sterically hindered acetal was crucial to good stereocontrol (Chart 1).Subsequent investigations have led to improved levels of stereocontrol. Herein, we detail our new findings along with a computational rationale for the improved levels of stereocontrol. Results and DiscussionAs we previously reported, 20) the reaction of (S)-Nbenzylidene-4-toluenesulfinamide (1a) with acetal 2 21) proceeded smoothly in the presence of trifluoroborane diethyl etherate using dimethylzinc-air to give a crude mixture including sulfinamide products 6a with a 9 : 1 diastereomeric ratio along with a trace amount of sulfonamide product 3a (ca. 1%). Subsequent oxidation of the crude products with m-chloroperbenzoic acid (m-CPBA) provided 3a with 80% ee in 92% yield (Table 1, entry 1). The enantiomeric ratio of 3a was the same as the diastereomeric ratio of 6a in the crude mixture, showing that no racemization took place during the m-CPBA oxidation.We reasoned that by substituting a bulkier group for the ptolyl group on the sulfur stereogenic center would presumably lead to higher levels of stereocontrol. In fac...

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“…Addition reaction of carbanions to the carbonyl group of aldehydes and ketones [1][2][3][4], and addition of organometallic reagents to the C=N bonds of imines or imine derivatives are important reactions in organic synthesis [5][6][7][8][9]. Another useful method for carbon-carbon bond formation is usage of alkynes as a carbon nucleophile source [10,11].…”

Section: Introductionmentioning

confidence: 99%