Total Synthesis of a Mycolic Acid from <i>Mycobacterium tuberculosis</i>

Tahiri, Nabil; Fodran, Peter; Jayaraman, Dhineshkumar; Buter, Jeffrey; Witte, Martin D.; Ocampo, Tonatiuh A.; Moody, D. Branch; Rhijn, Ildiko Van; Minnaard, Adriaan J.

doi:10.1002/ange.202000523

“…The Supporting Information is available free of charge on the Wiley VCH GmbH Publications website: Experimental protocols, nuclear magnetic resonance spectra, HPLC traces and X‐ray crystallographic data. Additional references are cited within the Supporting Information [30–59] …”

Section: Supporting Informationmentioning

confidence: 99%

Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

Ruyet,

Roblick,

Häfliger

et al. 2024

Angewandte Chemie

0

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Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C‐CF2‐C > ∠C‐CH2‐C): this provides a handle to modulate physicochemistry (e.g. pKa). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95% yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93:7 e.r.) together with X‐ray structural analyses and product derivatization.

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“…The Supporting Information is available free of charge on the Wiley VCH GmbH Publications website: Experimental protocols, nuclear magnetic resonance spectra, HPLC traces and X‐ray crystallographic data. Additional references are cited within the Supporting Information [30–59] …”

Section: Supporting Informationmentioning

confidence: 99%

Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

Ruyet,

Roblick,

Häfliger

et al. 2024

Angew Chem Int Ed

2

0

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Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C‐CF2‐C > ∠C‐CH2‐C): this provides a handle to modulate physicochemistry (e.g. pKa). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95% yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93:7 e.r.) together with X‐ray structural analyses and product derivatization.

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“…Thanks to the identical S configuration of C(2) and C (5), oxidative cleavage of unprotected central diol of 1 affords, with 100% atom economy, two molecules of (R)-2,3-Oisopropylideneglyceraldehyde (2) [1] and, upon reduction, of (S)-1,2-O-isopropylideneglycerol (3) [2,3], two of the most important C3-synthons within the chiral pool (Figure 1). Apart from their predictable wide use in the synthesis of the numerous molecules including the mono-, di-or trisubstituted glycerol framework, 2 and 3 are useful blocks to build other chiral linear molecules [4] and chiral cyclic systems. Examples of the latter are hexahydroindenes [5] benzomorpholines [6], benzodioxanes [7][8][9][10][11], dihydropyrroles [12], dihydrooxazines [12], dioxanes [13,14], pyridodioxanes [15,16], 2-oxazolidinones [17], spirobisdioxanes [18], and spirobisoxathianes [18].…”

Section: Introductionmentioning

confidence: 99%