In Situ Formation of Allyl Ketones via Hiyama−Nozaki Reactions Followed by a Chromium-Mediated Oppenauer Oxidation

Abstract

In Hiyama-Nozaki reactions of allylchromium with aldehydes the expected products are homoallylalcohols. However, oxidation products derived from these, predominantly allyl ketones, can be common side products. This can be explained by an Oppenauer-(Meerwein-Ponndorf-Verley)-type mechanism (OMPV-reaction). The amount of oxidation is strongly dependent on the substitution pattern of the reaction partners and the reaction conditions. An appropriate choice of these can lead to preferential formation of ketones instead of the alcohols. In addition to its synthetic usefulness, the oxidation-reduction equilibrium is of the utmost importance for the design of enantioselective Hiyama-Nozaki reactions because it is also a potential racemization pathway.

Involvement of an Oxidation‐Reduction Equilibrium in Chromium‐Mediated Enantioselective Nozaki–Hiyama Reactions

“…Benzaldehyde (1a) was distilled from potassium hydride. Spectral data of the known compounds 4a, [23] 4b, [24] 5a, [23] 5b, [25] and 5c [5] were in accordance with the literature data. Benzyl alcohol was characterized by comparison with a commercially available sample.…”

“…[3,10 ± 18] Interestingly, an OMPV-reaction also seems to participate in other chromium(II)-mediated reactions like the Nozaki±Hiyama À Kishi and chromium-Reformatsky reactions. [3,5,8] In accordance with this observation, OMPV equilibria are especially relevant in products from substituted allylchromiums, whereas good enantioselectivities were initially reported for the unsubstituted case only. This prompted us to look more closely into the relationship between enantioselective Nozaki±Hiyama reactions and OMPV transformations.…”

“…Although formally the same, the real nature of the intermediate chromium-alkyl and chromium alcoholate complexes is not understood at all, and it is well known that the complex formed [22] as well as the OMPV equilibrium [5] is strongly influenced by slight variations, e.g., of pH and aldehyde concentration. Thus, if the order of addition or ratio of the components is changed, cluster formation, incorporation of the second Cr(III) ion present, or binding of 6 or other ligands like aldehyde or THF in the active intermediate may be different.…”

“…[3,4] In our previous studies on the Nozaki±Hiyama reaction we observed that allyl ketones 4 can be common side products, or even the main product, although they are neglected by most authors. [5] This formation can be explained by an Oppenauer-type oxidation mechanism (Scheme 1) and is strongly favoured with sterically unhindered aromatic aldehydes and a substituted allylchromium. [5 ± 8] The involvement of an Oppenauer±Meer-wein À Ponndorf±Verley (OMPV) type oxidation-reduction equilibrium reaction implies dramatic consequences for enantioselective Nozaki±Hiyama reactions.…”

“…Also, in crossover experiments, in which anisaldehydes were used to form the Hiyama±Nozaki-intermediates 3, followed by excess benzaldehyde as oxidant, only the anisaldehyde-derived products were detected and not a mixture reflecting the proportions of the two aldehydes applied. [5] More extensive studies on the inhibition of retro-reactivity in Cr(III) complexes [3] will be published elsewhere.…”