Copper(I)-Catalyzed Enantioselective Boryl Substitution of Allyl Acylals: An Efficient Approach for Enantioenriched α-Chiral γ-Acetoxyallylboronates

Abstract

A novel approach has been developed for the enantioselective synthesis of α-chiral γ-acetoxyallylboronates via the copper(I)-catalyzed γ-boryl substitution of allyl acylals. This reaction proceeded with high E/Z selectivity and enantioselectivity (E/Z = >99:1, up to 80% yield, up to 99% ee). The subsequent allylation of aldehyde with the allylboronate afforded the monoprotected anti-1,2-diol derivative with high stereoselectivity.

Key words

boron - enantioselectivity - copper - catalysis - allylation

• References and Notes

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Representative examples of the routes used to synthesize the acetal and acylal substrates
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• 6b A Synthesis of Z-Allyl Acylal (Scheme 7) In contrast to the acetal substrates, the acylal substrates were much easier to prepare (b). The formylation of a terminal alkyne, followed by the gem-diacetylation of the resulting carbonyl moiety provided the corresponding propargyl acylals in moderate to high yields. The subsequent Z-selective reduction of the alkyne moiety in these propargyl acylals yielded the desired allylic substrates.
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• 13 Typical Procedure for the Enantioselective Boryl Substitution of Allyl Acylals CuCl (2.6 mg, 0.026 mmol), (R,R)-BenzP* (7.2 mg, 0.026 mol), B₂(pin)₂ (254.8 mg, 1.00 mmol), and KOt-Bu (84.3 mg, 0.75 mmol) were placed in a screw-capped test tube in a glove box under an argon atmosphere. After the vial was sealed with a screw cap containing a Teflon-coated rubber septum, the test tube was removed from the glove box and connected to a vacuum/nitrogen manifold through a needle. Then, dry DMI (1.0 mL) was added to the mixture via a syringe with stirring at r.t. After 15–30 min, acylal (Z)-1a (129.5 mg, 0.5 mmol) was added to the reaction mixture with vigorous stirring at 0 °C. After the completion of the reaction, the mixture was directly filtered through a short silica gel column with hexane–EtOAc (90:10) as the eluent. After removal of the solvents under reduced pressure, NMR yield was determined by ¹H NMR analysis of the crude reaction mixture [(S,E)-2a; 79%] by using mesitylene (26.7 mg, 0.22 mmol) as the internal standard. The crude product was purified with flash chromatography (SiO₂, hexane–Et₂O = 100:0 to 90:10) to give the corresponding γ-acetoxyallylboronate (S,E)-2a (84.8 mg, 0.257 mmol, 52% isolated yield). ¹H NMR (392 MHz, CDCl₃): δ = 1.25 (s, 12 H), 1.63–1.93 (m, 3 H), 2.11 (s, 3 H), 2.52–2.71 (m, 2 H), 5.45 (dd, J = 9.4, 12.5 Hz, 1 H), 7.09 (d, J = 12.2 Hz, 1 H), 7.13–7.31 (m, 5 H). ¹³C NMR (99 MHz, CDCl₃): δ = 20.7 (CH₃), 22.9 (br, BCH), 24.6 (CH₃), 24.7 (CH₃), 32.8 (CH₂), 35.0 (CH₂), 83.4 (C), 115.4 (CH), 125.6 (CH), 128.2 (CH), 128.4 (CH), 135.2 (CH), 142.3 (C), 168.1 (C). HRMS (EI): m/z [M]⁺ calcd for C₁₉H₂₇BO₄: 329.20387; found: 329.20481. [α]_D ²².² +5.4 (c 1.0, CHCl₃, 95% ee). The ee value was determined by HPLC analysis [Daicel CHIRALPAK OD-3, 2-PrOH–hexane = 0.25:99.75, 0.5 mL/min, 40 °C]: t _R (major) = 25.44 min; t _R (minor) = 24.83 min.
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