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. 2023 Oct 20;14(44):12684-12692.
doi: 10.1039/d3sc03081d. eCollection 2023 Nov 15.

Trialkylphosphonium oxoborates as C(sp3)-H oxyanion holes and their application in catalytic chemoselective acetalization

Vincent Ming-Yau Leung  1 , Hong-Chai Fabio Wong  1 , Chun-Man Pook  1 , Ying-Lung Steve Tse  1 , Ying-Yeung Yeung  1
Affiliations

Trialkylphosphonium oxoborates as C(sp3)-H oxyanion holes and their application in catalytic chemoselective acetalization

Vincent Ming-Yau Leung et al. Chem Sci. .

Abstract

The use of trialkylphosphonium oxoborates (TOB) as catalysts is reported. The site-isolated borate counter anion in a TOB catalyst increases the availability of C(sp3)-H to interact with electron donor substrates. The catalytic protocol is applicable to a wide range of substrates in the acetalization reaction and provides excellent chemoselectivity in the acetalization over thioacetalization in the presence of alcohols and thiols, which is otherwise hard to achieve using typical acid catalysts. Experimental and computational studies revealed that the TOB catalysts have multiple preorganized C(sp3)-Hs that serve as a mimic of oxyanion holes, which can stabilize the oxyanion intermediates via multiple C(sp3)-H non-classical hydrogen bond interactions.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Design of the trialkylphosphonium oxoborate as an oxyanion hole via strong C(sp3)–H NCHB. (A) Literature reports on using alkylonium salts as NCHB catalysts; (B) Literature reports on using arylphosphonium salts as Lewis acids; (C) Our previous study using amide/phosphonium zwitterions as catalysts; (D) The use of trialkylphosphonium oxoborate as a mimic of oxyanion holes for catalysis in this study.
Scheme 2
Scheme 2. Synthesis of the TOB catalysts.
Scheme 3
Scheme 3. Catalyst comparison in alcohol acetalization. Reaction conditions: reactions were carried out with benzyl alcohols (0.20 mmol), 3,4-dihydro-2H-pyran (2) (0.24 mmol) and catalyst in CDCl3 (0.4 mL) at 23 °C. The yields were measured by NMR with dibromomethane as the internal standard.
Scheme 4
Scheme 4. Substrate scope of acetalization. (A) Acetalization of dihydropyrans and dihydrofurans with alcohols; (B) Thioacetalization of dihydropyrans with thiols. Reaction conditions: reactions were carried out with alcohols or thiol (0.20 mmol), 3,4-dihydro-2H-pyran (2) (0.24 mmol) or 2,3-dihydrofuran (4) (0.24 mmol), and catalyst TOB-1 in CHCl3 (0.4 mL) for 18 h. a2.0 mmol scale. bThe reaction time is 48 h. cThe reaction time is 72 h.
Scheme 5
Scheme 5. Study on the O/S chemoselectivity in acetalization.
Scheme 6
Scheme 6. Examples of chemoselectivity acetalization.
Fig. 1
Fig. 1. Studies on the interactions between TOB-1 and BnOH. (A) NMR titration experiment with TOB-1 and BnOH; (B) comparison of the TOB-1 C(sp3)–H chemical shift in the presence of alcohols and thiols; (C) ESP analysis of TOB-1; (D) AIM analysis on the interactions between TOB-1 and BnOH; (E) NBO analysis on the interactions between TOB-1 and BnOH; (F) selected major E(2) stabilization energies of the C–H⋯O interactions.
Fig. 2
Fig. 2. Studies on the mechanism of chemoselective acetalization. (A) AIM analysis on the trilateral complex of TOB-1/4-Me–C6H4–OH/2; (B) AIM analysis on the trilateral complex of TOB-1/4-Me–C6H4–SH/2; (C) interactions among BF3 and the substrates; (D) plausible mechanism of the chemoselective acetalization.
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