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Synlett 2024; 35(04): 479-483
DOI: 10.1055/a-2161-9513
DOI: 10.1055/a-2161-9513
cluster
11th Singapore International Chemistry Conference (SICC-11)
Chiral Bifunctional Sulfide-Catalyzed Enantioselective Synthesis of α-Substituted γ-Lactones Bearing a γ-Quaternary Stereocenter
This work was supported by JSPS KAKENHI (Grant Number JP23K04752), the Joint Usage/Research Center for Catalysis (23DS0295), The Naito Foundation, the Fujimori Science and Technology Foundation, Naohiko Fukuoka Memorial Foundation, and the Nagasaki University WISE Program. This work was the result of using research equipment shared in the MEXT Project for promoting public utilization of advanced research infrastructure (Program for supporting introduction of the new sharing system) Grant Numbers JPMXS0422500320 and JPMXS0422300120.
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Abstract
Catalytic highly enantioselective syntheses of α-spiro-γ-lactones and α-substituted γ-lactones bearing a γ-quaternary stereocenter have been achieved through chiral bifunctional sulfide-catalyzed asymmetric bromolactonizations. The synthetic utility of the optically active γ-lactone products was demonstrated by transformations into functionalized γ-lactones and epoxides possessing a quaternary stereocenter.
Key words
asymmetric synthesis - halogenation - lactones - organocatalysis - sulfides - bromolactonizationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2161-9513.
- Supporting Information
Publication History
Received: 13 July 2023
Accepted after revision: 29 August 2023
Accepted Manuscript online:
29 August 2023
Article published online:
19 October 2023
© 2023. Thieme. All rights reserved
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- 7 Asymmetric Bromolactonization; General Procedure A solution of the appropriate substrate 2 (0.10 mmol) and catalyst (S)-1b (4.5 mg, 0.010 mmol, 10 mol %) in toluene (1.5 mL)–CH2Cl2 (0.5 mL) was cooled to –78 °C and stirred for 10 min at –78 °C. NBP (27.1 mg, 0.12 mmol, 1.2 equiv) was added to the cooled reaction solution and the resulting mixture was stirred for 24 h at –78 °C. The reaction was then quenched with sat. aq Na2SO3 (3 mL) at –78 °C and stirred for 10 min at –78 °C. The mixture was then diluted with CH2Cl2 (2 mL) and H2O (2 mL) and warmed to r.t. The organic materials were extracted with CH2Cl2 (3 × 5 mL), and the combined extracts were dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (silica gel) to give product 3. The enantioselectivities of the isolated products 3 were determined by HPLC analysis on a chiral stationary phase. (3R)-3-(Bromomethyl)-3-phenyl-2-oxaspiro[4.4]nonan-1-one (3b) Colorless oil; yield: 29.1 mg (94%); [α]D 21 +14.6 (c = 1.4, CHCl3; 94:6 er). HPLC [Daicel Chiralpak IC-3, hexane–2-propanol (20:1), flow rate = 0.5 mL/min, λ = 254 nm]: t R: 25.7 min (major); 36.8 min (minor). IR (neat): 2958, 1767, 1145, 1035, 996, 973, 767, 702 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.44–7.32 (m, 5 H), 3.73 (d, J = 11.2 Hz, 1 H), 3.65 (d, J = 11.2 Hz, 1 H), 2.77 (d, J = 13.0 Hz, 1 H), 2.55 (d, J = 13.0 Hz, 1 H), 2.27–2.20 (m, 1 H), 1.89–1.50 (m, 6 H), 1.26–1.18 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 181.2, 141.3, 128.7, 128.4, 125.0, 83.6, 50.1, 46.7, 41.1, 39.2, 38.0, 25.4, 25.2. HRMS (EI): m/z [M+] calcd for C15H17BrO2: 308.0412; found: 308.0412. (5R)-5-(Bromomethyl)-3,3-diethyl-5-phenyldihydrofuran-2(3H)-one (3g) Colorless oil; yield: 28.0 mg (90%); [α]D 25 +9.3 (c = 1.1, CHCl3; 97:3 er). HPLC [Daicel Chiralpak IE-3, hexane–2-propanol (20:1), flow rate = 0.5 mL/min, λ = 254 nm] t R = 28.2 min (minor); 30.5 min (major). IR (neat): 2968, 1768, 1120, 1032, 703 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.45–7.32 (m, 5 H), 3.71 (d, J = 11.2 Hz, 1 H), 3.62 (d, J = 11.4 Hz, 1 H), 2.80 (d, J = 13.3 Hz, 1 H), 2.44 (d, J = 13.5 Hz, 1 H), 1.75 (q, J = 7.6 Hz, 2 H), 1.39–1.25 (m, 2 H), 1.00 (t, J = 7.5 Hz, 3 H), 0.65 (t, J = 7.4 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 179.5, 141.8, 128.8, 128.4, 124.9, 83.0, 48.7, 42.1, 41.3, 29.2, 27.9, 8.8, 8.4. HRMS (EI): m/z [M+] calcd for C15H19BrO2: 310.0568; found: 310.0568.
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- 11 A transition-state model for the chiral bifunctional sulfide (S)-1b-catalyzed bromolactonization in the synthesis of γ-lactones bearing a γ-quaternary stereocenter is discussed in our previous report.3c