title: β-Selective C-Arylation of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis of Canagliflozin without Recourse to Conventional Protecting Groups.
abstract: The β-selective phenylation of benzyl and boronate protected 1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose (10), pretreated with i-Bu2AlH, i-Bu3Al, Et3Al, Me3Al, or n-octyl3Al, with triphenylalane or aryl(chloro)alanes is reported. The utility of the unprotected version of the method is demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin (1a), from commercially available 10 in one C-C bond-forming step. This approach circumvents the need for conventional protecting groups, and therefore no formal protection and deprotection steps are required.
authors.affiliation: ‡Department of Exploratory Research and §Department of Analytical Research and Development, ScinoPharm Taiwan, No. 1, NanKe 8th Road, Tainan Science-Based Industrial Park, ShanHua, Tainan, 74144 Tainan County, Taiwan.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Henschke
authors.affiliation: ‡Department of Exploratory Research and §Department of Analytical Research and Development, ScinoPharm Taiwan, No. 1, NanKe 8th Road, Tainan Science-Based Industrial Park, ShanHua, Tainan, 74144 Tainan County, Taiwan.
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: ‡Department of Exploratory Research and §Department of Analytical Research and Development, ScinoPharm Taiwan, No. 1, NanKe 8th Road, Tainan Science-Based Industrial Park, ShanHua, Tainan, 74144 Tainan County, Taiwan.
authors.forename: Ping-Yu
authors.initials: PY
authors.lastname: Wu
authors.affiliation: ‡Department of Exploratory Research and §Department of Analytical Research and Development, ScinoPharm Taiwan, No. 1, NanKe 8th Road, Tainan Science-Based Industrial Park, ShanHua, Tainan, 74144 Tainan County, Taiwan.
authors.forename: Wen-Shing
authors.initials: WS
authors.lastname: Tsao
authors.affiliation: ‡Department of Exploratory Research and §Department of Analytical Research and Development, ScinoPharm Taiwan, No. 1, NanKe 8th Road, Tainan Science-Based Industrial Park, ShanHua, Tainan, 74144 Tainan County, Taiwan.
authors.forename: Jyh-Hsiung
authors.initials: JH
authors.lastname: Liao
authors.affiliation: ‡Department of Exploratory Research and §Department of Analytical Research and Development, ScinoPharm Taiwan, No. 1, NanKe 8th Road, Tainan Science-Based Industrial Park, ShanHua, Tainan, 74144 Tainan County, Taiwan.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Chiang
mesh_terms: D000068896:Canagliflozin / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry*; D007004:Hypoglycemic Agents; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*
chemical_list: D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D000068896:Canagliflozin; C035719:diisobutylaluminum; D005947:Glucose