Phosphine‐Catalyzed Enantioselective Synthesis of Oxygen Heterocycles

Abstract

Chiral phosphepine 1 catalyzes the transformation of an array of hydroxy-2-alkynoates into saturated oxygen heterocycles with good enantioselectivity. Phenols are also shown to participate in such phosphine-catalyzed cyclizations, including an asymmetric variant. This method provides a new approach to the enantioselective synthesis of tetrahydrofurans, tetrahydropyrans, and dihydrobenzopyrans.

Enantioselective Phosphine Organocatalysis

“…Moreover, chiral diphosphines may totally lose their discriminating ability when lacking the chelated arrangement they usually display in the coordination sphere of a metal. Thus, it is not really surprising that screenings of commercially available chiral phosphines, such as atropisomeric diphosphines, [14][15][16] 1,2-bis[2-anisyl(phenyl)phosphino]ethane (DIPAMP), [17][18][19] 4,5-bis[(diphenylphosphino)methyl]-2,2-dimethyl-1,3-dioxolane (DIOP), 18 and others, [20][21][22] in organocatalytic processes met with only moderate success in terms of catalytic activity and enantioselectivity. Notable exceptions are represented by bidentate phosphines, such as 1,2-bis(2,5-diethylphospholano)ethane (Et-BPE), 23 1,2-bis(2,5-diethylphospholano)benzene (Et-DuPHOS), 24 and BI-NAPHANE, 25 which because of their cyclic structures can be legitimately included in one of the two classes of wellsuited phosphorus organocatalysts, known so far.…”

Enantioselective Allylic C−H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis

“…[8] Enantioselective organocatalytic and metal-catalyzed methods are emerging to furnish this motif, however, generally starting from pre-oxidized precursors. [9] We recently reported the synthesis of racemic cyclic ethers via Pd(II)/bis-sulfoxide-catalyzed, BQ-promoted allylic C–H oxidation. [10] Given that pre-coordination of the alcohol to Pd was found to be important for functionalization, we hypothesized that such a system might enable high levels of asymmetric induction in the C–O bond forming step, and provide a valuable means to furnish chiral isochromans.…”

Phosphine-Catalyzed β′-Umpolung Addition of Nucleophiles to Activated α-Alkyl Allenes

“…Since the first report by Trost, 2 there has been increasing interest in phosphine-catalyzed γ-umpolung additions of pronucleophiles to electron-deficient alkynes and allenes (Scheme 1; eq 1). 3 Combining the mechanistic insights gained from studies of the γ-umpolung additions and nucleophilic phosphine–catalyzed reactions of α-substituted allenoates developed in our laboratory 4 and by others, 5 we envisaged the possibility of a β′-umpolung addition to α-alkyl allenoates (Scheme 1; eq 2). This process facilitates functionalization of the seemingly unactivated β′-C–H bond, allowing the generation of unique, highly versatile olefinic products.…”