The stereodivergent construction of cyclic ethers remains an important area of synthetic interest, particularly given the ubiquity of C-glycoside derivatives in natural and unnatural pharmacologically important agents. 1 Bismuth(III) halides are inexpensive and environmentally benign reagents, which have been utilized as mild Lewis acid catalysts for an array of synthetic transformations. 2,3 Herein, we describe a series of stereoselective intramolecular etherification reactions of δ-trialkylsilyloxy aldehydes and ketones 1, using catalytic bismuth tribromide and various trialkylsilyl nucleophiles for the construction of cisand trans-2,6-di-and trisubstituted tetrahydropyrans 2 (eq 1). 4The mechanistic hypothesis, outlined in Scheme 1, describes the basis of the two-component etherification reaction. Since bismuth-(III) trihalides are known to readily undergo hydrolysis to afford bismuth oxyhalides and the requisite Brønsted acid, 2,5 we anticipated that the latter would promote the formation of ii, which should then undergo in situ desilylation to afford the lactol iii. 6 Acidcatalyzed dehydration of iii could then lead to the formation of the oxocarbenium ion iv and facilitate axial nucleophilic attack to furnish the cyclic ether v. 7 The potential advantage of this approach over that involving a Lewis acid is the unusual chemoselectivity, which will provide a powerful tool for the construction of cyclic ethers. This selectivity is presumably the result of the low reactivity of the protonated carbonyl, which requires addition of the pendant triorganosilyloxy group to afford the more reactive oxocarbenium ion. 8 Moreover, the acid concentration is modulated using the hydrolysis of the triorganosilyl halide, making it an exceedingly mild and convenient method.Preliminary studies demonstrated that the nature of the bismuth-(III) halide was inconsequential in terms of both efficiency and selectivity (Cl ∼ Br ∼ I). In light of this fact we elected to utilize the less expensive BiBr 3 . Interestingly, while the selectivity was unaffected by the nature of the triorganosilyl ether, the efficiency of the reaction was found to be directly related to the rate of protodesilylation (TMS ∼ TES > TBS >> TIPS). 9 Additional studies using pendant triethylsilyl ethers then focused on providing evidence for the proposed hypothesis outlined in Scheme 1. Initial studies examined the proposal that BiBr 3 or triethylsilyl bromide provided a source of HBr, which then functions as the catalyst (Table 1, entries 1, 5, and 7). Consistent with this hypothesis, the addition of water to BiBr 3 did not prove detrimental to the reaction and further supports the notion that the BiBr3 is not acting as a Lewis acid (entry 2). Moreover, the addition of activated molecular sieves to each of these reagents, to sequester HBr and water, gave none of the desired product (entries 3, 6, and 8). NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 4). The relatively poor catalytic activity of HBr and triethylsilyl bromide (entries...

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A general strategy toward the synthesis of aryliodonium triflate salts has been exploited to afford derivatives that incorporate thiophene and bithiophene components. Both mono- and bis(iodonium) salts have been realized, and a series of bithienyl(aryl)iodonium triflates with increasingly electron-withdrawing substituents on the aryl moiety have been synthesized. X-ray crystallographic analysis of four derivatives (4a, 4b, 6b, and 8c) demonstrates that the solid-state organization of these salts incorporates extensive networks of secondary bonding interactions between the cationic iodonium centers and the triflate counterions. UV-vis spectroscopic analysis shows that the electronic interactions between pendent aryl and heteroaryl groups across the iodonium center can be dictated by substitution. Furthermore, the energy of the HOMO-LUMO gap decreases substantially in weakly or noncoordinating solvents.