title: Brønsted acid-catalyzed intramolecular nucleophilic substitution of the hydroxyl group in stereogenic alcohols with chirality transfer.
abstract: The hydroxyl group of enantioenriched benzyl, propargyl, allyl, and alkyl alcohols has been intramolecularly displaced by uncharged O-, N-, and S-centered nucleophiles to yield enantioenriched tetrahydrofuran, pyrrolidine, and tetrahydrothiophene derivatives with phosphinic acid catalysis. The five-membered heterocyclic products are generated in good to excellent yields, with high degree of chirality transfer, and water as the only side-product. Racemization experiments show that phosphinic acid does not promote SN1 reactivity. Density functional theory calculations corroborate a reaction pathway where the phosphinic acid operates as a bifunctional catalyst in the intramolecular substitution reaction. In this mechanism, the acidic proton of the phosphinic acid protonates the hydroxyl group, enhancing the leaving group ability. Simultaneously, the oxo group of phosphinic acid operates as a base abstracting the nucleophilic proton and thus enhancing the nucleophilicity. This reaction will open up new atom efficient techniques that enable alcohols to be used as nucleofuges in substitution reactions in the future.
authors: †Department of Chemistry, BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden.
authors: Anon
authors: A
authors: Bunrit
authors: †Department of Chemistry, BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden.
authors: Christian
authors: C
authors: Dahlstrand
authors: †Department of Chemistry, BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden.
authors: Sandra K
authors: SK
authors: Olsson
authors: †Department of Chemistry, BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden.
authors: Pemikar
authors: P
authors: Srifa
authors: ‡Department of Organic Chemistry, Stockholm University, 106 91 Stockholm, Sweden.
authors: Genping
authors: G
authors: Huang
authors: §Department of Chemistry, Ångström Laboratories, Uppsala University, Box 523, 75120 Uppsala, Sweden.
authors: Andreas
authors: A
authors: Orthaber
authors: †Department of Chemistry, BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden.
authors: Per J R
authors: PJ
authors: Sjöberg
authors: †Department of Chemistry, BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden.
authors: Srijit
authors: S
authors: Biswas
authors: ‡Department of Organic Chemistry, Stockholm University, 106 91 Stockholm, Sweden.
authors: Fahmi
authors: F
authors: Himo
authors: †Department of Chemistry, BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden.
authors: Joseph S M
authors: JS
authors: Samec