tert-Butoxide-Mediated Protodeformylative Decarbonylation of α-Quaternary Homobenzaldehydes

Abstract

tert-Butoxide mediates the Haller–Bauer-type (protodeformylative) decarbonylation of readily accessed α-quaternary homobenzaldehydes and related compounds at room temperature, generating cumene products. Both geminal dialkyl and geminal diaryl substituents are tolerated. gem-Dimethyls are sufficient for decarbonylation of polycyclic arenyl substrates whereas monocyclic aromatic homobenzaldehydes require cyclic gem-dialkyls or gem-diaryls for significant decarbonylation.

Key words

decarbonylation - C–C bond cleavage - protodeformylation - Haller–Bauer reaction - tert-butoxide - benzylic anion - cumenes

Publikationsverlauf

Eingereicht: 05. September 2023

Angenommen nach Revision: 04. Dezember 2023

Accepted Manuscript online:
18. Dezember 2023

Artikel online veröffentlicht:
19. Januar 2024

• References and Notes


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• 19 As further mechanistic support, two deuterium labeling experiments (one employing deuterated aldehyde as substrate, the other employing THF-d ₈ as solvent) both afforded no detectable deuterium incorporation in the product.
• 20 See the Supporting Information for details.
• 21 Protodeformylation; General Procedure: An oven-dried 25-mL round-bottom flask was charged with a PTFE-coated magnetic stir bar, fitted with a rubber septum, and purged with nitrogen for 2 min. Then, under ambient pressure of N₂, KOt-Bu solution (1.6 M in THF, 0.3 mmol, 1.6 equiv, 0.2 mL) was added to the flask, and further diluted with anhydrous THF (1.0 mL). To the flask, an anhydrous THF solution of aldehyde (0.2 M, 1.0 equiv, 1.0 mL) was added dropwise at room temperature. The mixture was then allowed to stir for 5 h under ambient pressure of N₂. The reaction was diluted with EtOAc (2 mL), saturated aqueous NH₄Cl (5 mL) was added, and the mixture was allowed to stir until the solution became decolored. The aqueous layer was then extracted with EtOAc (3 × 5 mL) and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford the crude decarbonylated product, which was then purified by silica gel chromatography.
• 22 Characterization data of representative product 4b: Yield (1.0 mmol scale): 158 mg (93%); colorless oil. ¹H NMR (500 MHz, CDCl₃): δ = 8.16 (dd, J = 8.5, 1.2 Hz, 1 H), 7.90–7.84 (m, 1 H), 7.73 (dt, J = 7.8, 1.1 Hz, 1 H), 7.62–7.38 (m, 4 H), 3.79 (sept, J = 6.9 Hz, 1 H), 1.44 (d, J = 6.9 Hz, 6 H). ¹³C NMR (125 MHz, CDCl₃): δ = 144.6 (C), 133.9 (C), 131.3 (C), 128.9 (CH), 126.3 (CH), 125.7 (CH), 125.6 (CH), 125.2 (CH), 123.3 (CH), 121.7 (CH), 28.5 (C), 23.6 (CH₃)..
• 23 Cai X.; Stokes B. J. ChemRxiv; 2021, preprint; DOI: 10.26434/chemrxiv-2021-q22x8