Dehomologative C-C Borylation of Aldehydes and Alcohols via a Rh-Catalyzed Dehydroformylation-Borylation Relay

Abstract

The dehomologative conversion of linear or α-methyl aldehydes to vinyl boronates is achieved via a one-pot sequence of rhodium-catalyzed transfer dehydroformylation and transfer borylation of the resulting alkenes. Similarly, allylic or aliphatic alcohols are converted to vinyl boronates through a sequence involving, respectively, rhodium-catalyzed isomerization or transfer dehydrogenation to aldehyde intermediates, followed by dehydroformylation-borylation. The vinyl boronates can be further hydrogenated to alkyl boronates using the same rhodium precatalyst, enabling all five catalytic steps with a single catalyst system.

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Context of the current work.

1. Envisioned C–C bond Borylation of Aldehydes under Rh-Catalyzed Relay

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Transforming aldehydes into vinyl boronates via dehydroformylation-borylation sequence carried out under relay catalysis versus sequentially in one pot (a) and the scope of liner and α-methyl aldehydes under relay catalysis (b and c). Because vinylboronic esters tend to overadsorb and partially decompose during chromatography on silica gel, especially when isolated on small scale, the NMR or GC yields are reported here to indicate the actual reaction performance. For isolated yields, NMR yields of intermediates, and the presence of potential side products, as well as the reactions under varied conditions, see Figure S1. ^a Full conversion of the aldehyde was observed after 2 h; vBpin was added, and the reaction continued for 8 h (Section S9). ^b 6 mol % Rh, at 130 °C. ^c After 6 h, the reaction mixture was filtered through a plug of silica, followed by adding 4 mol % Rh and vBpin (0.25 mmol), and the reaction continued for 6 h. ^d After 2 h, 4 mol % Rh and vBpin were added, and the reaction continued for 6 h.

2. Envisioned C–C Bond Borylation of Allylic and Aliphatic Alcohols under Rh-Catalyzed Relay

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Transforming allylic alcohols into dehomologated vinyl boronates via the isomerization–dehydroformylation–borylation sequence. NMR yields reported; for all data, see Figure S2. ^a The reaction was performed at 120 °C for 2 h, followed by addition of 4 mol % Rh catalyst and vBpin (0.25 mmol), and continued for 8 h. ^b The reaction mixture contained a substantial amount of alkene intermediate; the mixture filtered through a plug of silica, followed by adding 4 mol % Rh catalyst and vBpin (0.25 mmol), and the reaction continued for 8 h. ^c 120 °C.

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Transforming linear and β-methyl aliphatic alcohols into dehomologated or demethylated vinyl boronates via dehydrogenation-dehydroformylation-borylation. NMR yields reported; for all details, see Figure S3. ^a Reagents added in three portions; 2nd and 3rd portions added after 2 and 9 h, respectively; 3rd portion added after the mixture filtered through a plug of silica, and the reactions continued for 7 h. ^b vBpin added only after 2 and 9 h.

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Gram scale experiments. Isolated amounts and yields were reported.

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Transforming aldehydes and alcohols into alkyl boronates incorporating telescoped Rh-catalyzed hydrogenation of vinyl boronate intermediates. Isolated yields reported (no analytical yields available). (i) Aldehyde/alcohol (0.2 mmol) converted into a vinyl boronate under conditions shown in Figures –, (ii) + thf (0.4 mL), H₂ (1–5 bar), 60 °C, 16 h.