Catalyst-Controlled Wacker-Type Oxidation of Homoallylic Alcohols in the Absence of Protecting Groups

Abstract

Homoallylic alcohols are oxidized to β-hydroxy ketones using a TBHP-mediated Pd-catalyzed Wacker-type oxidation. The use of a bidentate ligand, quinoline-2-oxazoline (Quinox), and TBHP(aq) as the terminal oxidant provides good yields of the desired products with reaction times significantly reduced as compared to the Tsuji-Wacker oxidation. Additionally, bis- and tris-homoallylic alcohols are oxidized to provide cyclic peroxyketals, presumably via nucleophilic attack of the methyl ketone product.

Oxidation and Reduction

“…The bis-and tris-homoallylic alcohols were oxidized to cyclic peroxyketals, presumably via nucleophilic attack of the methyl ketone. 145 Kinetics of the Wacker-type oxidation of olefins by TBHP in the presence of Quinox (ligand), and (54) as the catalyst reveal first-order dependence on ligand and olefin, and rate saturation in TBHP, as expected of the proposed mechanism (Scheme 9)…”

“…The intermediate (143) was presumably generated via trifluoroacetylation of a sulfoxide precursor (142). Ionization of trifluoroacetate generated a dipositive 'sulfenium' equivalent (144), which transformed to (145). The treatment of (145) with trifluoroacetate resulted in the bridged sulfonium trifluoroacetate (146) and subsequently to the corresponding sulfenium tetrafluoroborate (147).…”

ChemInform Abstract: Peroxide‐Mediated Wacker Oxidations for Organic Synthesis

“…A number of transition metals, including iridium, 27 ruthenium, 28,29 platinum, 30 rhodium, 5,6,20,22,24,26,29,31–46 and palladium, 23,25,26,47–61 have been reported to either activate molecular oxygen or use exogenous peroxide to convert terminal olefins to methyl ketones. Significantly, the seminal systems involve rhodium, while palladium systems appear to have the greatest synthetic potential.…”

“…57,58,60,61 As a result of these investigations, a highly selective oxidation system was developed and will be discussed below.…”

“…Through empirical optimizations, a highly active catalyst system was developed, which oxidized terminal olefins selectively to their methyl ketone products (Table 4). 57,58,61 The Quinox ligand is readily prepared from simple starting materials (Scheme 4) 57,58 and is also commercially available. Substrates, such as protected allylic alcohols 57 and amines, 58 as well as unprotected homoallylic alcohols 61 are selectively oxidized with catalyst-control using the Pd(quinox)-TBHP system.…”