Recent advancements in the use of Bobbitt's salt and 4-acetamidoTEMPO

Abstract

This feature article provides a comprehensive overview of recent developments and applications of Bobbitt's salt and 4-acetamidoTEMPO in organic synthesis and fields beyond.

Asymmetric Synthesis of Nidulalin A and Nidulaxanthone A: Selective Carbonyl Desaturation Using an Oxoammonium Salt

“…This control experiment reinforced a desaturation mechanism involving the ester n(O)-to-σ*(C−H) activation rather than the allylic π(C�C)-to-σ*(C−H) activation. 36 At present, we cannot rule out a mechanism involving enol formation from substrate 2 followed by desaturation by oxoammonium salt 30 which was also proposed in the literature. 33,34 Although DFT computations (r 2 SCAN-3C/ CPCM (CH 2 Cl 2 )) showed that the enol desaturation is almost barrierless (TS-SB, 2.3 kcal/mol), 9 we were unable to identify an energetically reasonable enolization process.…”

“…Although allylic alcohols tend to be reactive toward such reagents, , we reasoned that the ester of 2 might prevent alcohol oxidation, as we only recovered starting material 2 after treatment with DDQ. Based on a literature search that identified Bobbitt’s oxoammonium salt 30 as a stoichiometric reagent for both oxidation of alcohols and desaturation of ketones, − we found that 30 cleanly converted allylic alcohol 2 to nidulalin A ( 1 ) in 78% yield in refluxing DCE without alcohol oxidation (Figure A). On the other hand, use of AZADO-BF 4 32 resulted in decomposition, and TEMPO-BF 4 31 only resulted in a lower yield of 1 along with unidentified byproducts.…”

“…Given that Bobbitt’s salt 30 is known to serve as a hydride acceptor, , together with the premise that an ester n­(O)-to-σ*­(C–H) interaction should activate the hydrogen β to the ketone based on computational analysis of 2 ( left inset , Figure ), we considered that desaturation of successful substrates 2 and 17 may occur by a hydride transfer mechanism which is facilitated by the adjacent ester moiety. Accordingly, we hydrogenated substrate 17 to 35 (Figure C) to remove the cyclohexenyl moiety.…”

The Catalytic Enantioselective [1,2]-Wittig Rearrangement of Allylic Ethers

“…As [1,2]-Wittig products are traditionally expected to be generated via a radical recombination mechanism the effect of adding 20 mol% of 4-NHAc-TEMPO as an additive was probed. Formation of the [1,2]-product was not significantly inhibited, giving 9 in 73% yield and improved 95:5 er, with no 4-NHAc-TEMPO adducts observed 33 . The mass balance consisted of the aldol side product 10 (>95:5 dr, 75:25 er) that was isolated in 5% yield; addition of 1.0 equivalent of 4-NHAc-TEMPO was also tested, affording 9 in a further reduced 59% yield but enhanced 97:3 er.…”