Regiocontrol in the Oxidative Radical Fragmentation of Benzilidene Acetals and Its Mechanistic Implications

Abstract

The NBS-mediated oxidative fragmentation of benzilidene acetals has been investigated with mechanistic probes 12, 14, and 18 designed to discriminate between the possible competitive pathways. Results indicate that fragmentation of the initial benzylic radical 19 does not occur spontaneously but that oxidation proceeds rapidly to give the benzyl bromide 20, which then fragments via a polar pathway. Reversed regiospecificity in the fragmentation is demonstrated for the first time through the incorporation of an allylic alcohol into the benzilidene acetal.

Scope and Mechanistic Insights into the Use of Tetradecyl(trihexyl)phosphonium Bistriflimide: A Remarkably Selective Ionic Liquid Solvent for Substitution Reactions

“…[5] We have previously demonstrated phosphonium-based ILs to be efficient and recyclable media for Pd-mediated cross-coupling reactions. [10,11] We also demonstrated the ability of the quaternary phosphonium ion to expand its valency and function as a mild Lewis acid, [12] thus promoting carbonyl-addition reactions. Phosphonium-based ILs are very stable thermally, [13] are stable towards strongly basic reagents including Grignard reagents (it has been shown that ylide formation does not occur readily in the pure IL, even in the presence of strongly basic Grignard reagents), [14] and are not susceptible to aromatic substitution chemistry.…”

“…We next extended the substitution reaction to weaker nucleophiles including nitrite, carboxylate, and phenolate anions as indicated in Table 1 (entries [9][10][11][12][13][14]. Nitroalkanes are amongst the most versatile of intermediates in organic synthesis in view of their high reactivity and versatility in terms of the subsequent conversions that are possible.…”

Regioselective Ring Opening of 1,3‐Dioxane‐Type Acetals in Carbohydrates

“…Remarkably, both researchers proposed another mechanistic pathway to account for the observed reaction products: Hanessian promoted the ionic route, in which an intermediate oxocarbenium ion is formed, whereas Hullar favored the radical pathway. In 2004, McNulty et al conducted some control experiments, indicating that the fragmentation most likely proceeds through an ionic mechanism (Scheme ) . Since NBS can generate bromine (Br 2 ) in situ by reaction with HBr, which is present in low concentrations, the first step includes the abstraction of a radical hydrogen from the arylidene acetal carbon atom by a bromine radical to give acetal radical 8 .…”

“…In 2004, McNulty et al conducted some control experiments, indicating that the fragmentation most likely proceeds through an ionic mechanism (Scheme 4). [53] Since NBS can generate bromine (Br 2 ) in situ by reaction with HBr, which is present in low concentrations, the first step includes the abstraction of a radical hydrogen from the arylidene acetal carbon atom by a bromine radical to give acetal radical 8. This is followed by a propagation step, during which bromination of the acetal radical takes place (Wohl-Ziegler bromination).…”

Phosphonium Salt Organocatalysis

“…The key to the successful application of phosphonium salts as Lewis acidic catalysts is the utilization of hypervalent bonding between a Lewis basic substrate and the Lewis acidic catalyst to generate an activated species (Scheme 2). [25,26] The n-s* interaction between a non-bonding electron pair of the Lewis base and the anti-bonding orbital with s character of the Lewis acid requires the Lewis acidic acceptor to be able to expand its coordination sphere to attain a hypervalent state. [10,27] The formed hypervalent bond is stabilized when an electron-withdrawing substituent occupies the apical position of the trigonal bipyramidal arrangement.…”