Insight into the Ferrier Rearrangement by Combining Flash Chemistry and Superacids

• Published in: Angewandte Chemie International Edition Vol. 60; no. 4; pp. 2036 - 2041
• Main Authors: Bhuma, Naresh, Lebedel, Ludivine, Yamashita, Hiroki, Shimizu, Yutaka, Abada, Zahra, Ardá, Ana, Désiré, Jérôme, Michelet, Bastien, Martin‐Mingot, Agnès, Abou‐Hassan, Ali, Takumi, Masahiro, Marrot, Jérôme, Jiménez‐Barbero, Jesús, Nagaki, Aiichiro, Blériot, Yves, Thibaudeau, Sébastien
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.01.2021; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Edition: International ed. in English
• Subjects: Aromatic compounds; C-glycoside; Chemical Sciences; Chemistry; Chemistry, Multidisciplinary; Ferrier rearrangement; Glycosides; glycosylation; Ions; Mathematical analysis; NMR; Nuclear magnetic resonance; Organic chemistry; oxycarbenium; Physical Sciences; Science & Technology; Structural analysis; superelectrophiles; GLYCOSIDES; superelectrophiles; oxycarbenium; CATION-FLOW METHOD; glycosylation; GLYCALS; 2,3-UNSATURATED C; CLAISEN REARRANGEMENT; ALLYLTRIMETHYLSILANE; C-glycoside; PRODUCTS; GENERATION; Ferrier rearrangement; CYCLIZATION
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202010175

The transformation of glycals into 2,3‐unsaturated glycosyl derivatives, reported by Ferrier in 1962, is supposed to involve an α,β unsaturated glycosyl cation, an elusive ionic species that has still to be observed experimentally. Herein, while combination of TfOH and flow conditions failed to observe this ionic species, its extended lifetime in superacid solutions allowed its characterization by NMR‐based structural analysis supported by DFT calculations. This allyloxycarbenium ion was further exploited in the Ferrier rearrangement to afford unsaturated nitrogen‐containing C‐aryl glycosides and C‐alkyl glycosides under superacid and flow conditions, respectively. The cyclic allyloxycarbenium ion, the key intermediate in the Ferrier rearrangement, has been generated and accumulated under TfOH flow conditions. It is stable in superacid HF/SbF5 solutions. Its long‐lived character in these non‐nucleophilic conditions allowed its full characterization by low‐temperature NMR supported by DFT calculations. This ionic species produced a range of original C‐aryl and C‐heteroaryl pseudoglycals.