Unsymmetrical E-Alkenes from the Stereoselective Reductive Coupling of Two Aldehydes

Abstract

The unprecedented formation of unsymmetrical alkenes from the intermolecular reductive coupling of two different aldehydes is described. In contrast to the McMurry reaction which affords statistical product mixtures, selectivity in the reported procedure is achieved by a sequential ionic mechanism in which a first aldehyde is reacted with a phosphanylphosphonate to afford a phosphaalkene intermediate which, upon activation by hydroxide, reacts with a second aldehyde to the unsymmetrical E-alkenes. The described reaction is free of transition metals and proceeds under ambient temperature within minutes in good to excellent overall yields. It is a new methodology to use feedstock aldehydes for the direct production of C═C double bond-containing products and may impact how chemists think of multistep synthetic sequences in the future.

Reactivity patterns of benzhydryl(mesityl)phosphane oxide – a potential intermediate in carbonyl-carbonyl coupling reactions?

“…[11][12][13] In contrast to the McMurry protocol [14] which uses low-valent transitional metals, requires harsh reaction conditions, and does not allow the selective preparation of unsymmetric alkenes from the coupling of two non-identical carbonyl compounds, our approach proceeds by a stepwise anionic mechanism which resolves the drawbacks mentioned above. In our synthetic methodology, [11] a first aldehyde reacts with a lithiated phosphanylphosphonate to obtain phosphaalkenes in which the C-center of the P ¼ C double bond exhibits an opposite polarization compared to that in the starting carbonyl compound (Figure 1b). As a consequence of this Umpolung, treatment of the phosphaalkene with a Bu 4 NOH solution results in the formal addition of water to the P ¼ C double bond with a hydroxyl group placed at the Pcenter.…”

Triarylalkenes from the site-selective reductive cross-coupling of benzophenones and aldehydes

“…Li and co-workers published a Ru-catalyzed process in which hydrazine acts as reductant and oxygen acceptor. 9 At the same time, we reported the first transition metal-free, siteselective coupling of two aldehydes to alkenes, 10 in which siteselectivity is achieved by the sequential addition of the carbonyl compounds at different stages of the one-pot reaction. The reaction proceeds by an ionic mechanism, and occurs at room temperature in less than one hour.…”

“…To this end, we have developed and reported reagents and activation procedures for the coupling of mainly aromatic aldehydes, irrespective of their electronic nature. 10,14 The reductive coupling of aldehydes to ketones to generate trisubstituted alkenes has remained largely elusive. 14b In the present paper, we report the first example of a reagent that broadly promotes this chemistry, and demonstrate its potential for the reductive coupling of benzophenones and aromatic aldehydes to triarylalkenes.…”

Reductive coupling of two aldehydes to unsymmetrical E-alkenes via phosphaalkene and phosphinate intermediates

“…20,21 Recently, we reported a new methodology for the selective reductive cross-coupling of two aldehydes to unsymmetrical E-alkenes. 22 This new reaction makes use of an organophosphorus reagent, more specifically a phosphanylphosphonate 1-H, 23 and achieves selectivity by the sequential addition of the two aldehyde substrates. The first aldehyde reacts with 1 to form a phosphaalkene intermediate 2 in a phosphorus version of the HWE reaction 24,25 (Scheme 1, step 1).…”

“…This phosphine oxide intermediate 5 is structurally analogous to Horner-Wittig reagents 26 and reacts with a second aldehyde to form the olefinic product 6 under basic conditions. 22 In comparison to the McMurry coupling, this new one-pot reaction works at room temperature within minutes. It has high selectivity for the formation of E-alkenes, and most importantly, it gives direct access to unsymmetrical alkenes from two non-identical aldehydes.…”