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Article Dans Une Revue Organic Letters Année : 2020

Redox-Neutral 1,3-Diol Synthesis by Base-Promoted Diastereoselective Alcohol–Aldolization

Résumé

In order to prepare more efficiently key 1,3-diol fragments, we have devised a base-promoted redox-neutral condensation of ketones with alcohols. This diastereoselective alcohol−aldolization enables bypassing the classical oxidation and reduction steps necessary for the preparation of this crucial backbone by an overall redox-neutral formal borrowing hydrogen process. The starting alcohols constitute both the precursors of the in situ generated reactive aldehydes and the hydride source necessary for the chemoselective reduction of the aldol adduct intermediates. I n order to minimize steps and waste generation associated with the stereoselective elaboration of complex organic scaffolds, the invention of redox-neutral approaches is crucial. 1 These transformations, such as the popular borrowing hydrogen , have the power to avoid unnecessary operations and stoichiometric reagents associated with stepwise oxidation and reduction sequences, a step further toward eco-compatible synthesis. 2 The elaboration of 1,3-diols, a common motif found in a wide variety of natural products and drugs (Scheme 1a), is a classic example of a synthetic sequence often involving successive undesired redox steps. 3 This key architecture is usually constructed via aldol reaction between a carbonyl and an aldehyde (Scheme 1b). However, the starting aldehyde is often prepared by oxidation of the corresponding alcohol, and the aldol adduct must then be reduced to form the desired 1,3-diol. As a result, such a sequence implies two undesired time-and energy-consuming redox steps. In order to limit redox issues, different alternatives have been proposed such as the aldol Tishchenko-type disproportionation. However, this reaction occurs from the aldehyde oxidation level and requires an additional equivalent of aldehyde to promote the reduction of the aldol product through intramolecular hydride transfer. 4 Most interestingly, a broad range of elegant metal-catalyzed redox-neutral couplings have been developed such as the allylations of alcohols. 5 While these strategies elegantly enable constructing alcohols directly from the same oxidation state, further derivatizations of the obtained alkenes through redox manipulation is mandatory to obtain complex polyol scaffolds. Given 1,3-diols oxidation state, in order to obtain the best synthetic ef f iciency, their elaboration should imply a redox-neutral cascade construction by aldol condensation directly between a ketone and an alcohol. Inspired by the synthetic economies provided by borrowing hydrogen approaches, we present a new conceptual alcohol−aldolization for the direct construction of anti-1,3-diols

Domaines

Chimie organique
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Dates et versions

hal-02953855 , version 1 (30-09-2020)

Identifiants

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Na Shao, Jean Rodriguez, Adrien Quintard. Redox-Neutral 1,3-Diol Synthesis by Base-Promoted Diastereoselective Alcohol–Aldolization. Organic Letters, 2020, 22 (18), pp.7197-7201. ⟨10.1021/acs.orglett.0c02536⟩. ⟨hal-02953855⟩

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