Synlett 2017; 28(13): 1660-1662
DOI: 10.1055/s-0036-1588418
letter
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (+)-Mintlactone and (–)-Isomintlactone via SmI2-Induced Radical Cyclization

Xiaodong Wang ◊
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
,
Huihong Wang ◊
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
,
Xia Wu
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
b   State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. of China
,
Tianqun Yu
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
,
Weiwei Gao
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
,
Tao Shi
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
,
Xue Peng
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
,
Dian He*
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
,
Zhen Wang*
a   School of Pharmacy, Lanzhou University, West Donggang Road. No. 199, Lanzhou 730000, P. R. of China   Email: hed@lzu.edu.cn   Email: zhenw@lzu.edu.cn
b   State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. of China
› Author Affiliations
Supported by: Fundamental Research Funds for the Central Universities 223000/862413
Further Information

Publication History

Received: 03 January 2017

Accepted after revision: 18 April 2017

Publication Date:
04 May 2017 (online)


These authors contributed equally

Abstract

A divergent strategy has been used to concisely and efficiently complete the synthesis of (+)-mintlactone and (–)-isomintlactone via SmI2-induced intramolecular radical cyclization, two rings and a stereocenter were constructed in one step. In the synthesis, the stereochemistry of the final natural product is set relative to the stereocenter of (–)-citronellol and favored coordination transition state of samarium atom with substrate.

Supporting Information

 
  • References and Notes

  • 1 Procter DJ. Flowers RA. II. Skrydstrup T. Organic Synthesis Using Samarium Diiodide: A Practical Guide . RSC Publishing; Cambridge: 2009
  • 2 Iwabuchi H. Abstracts of Papers: 41st Symposium on the Chemistry of Terpenes, Essential Oils, and Aromatics. Morioka; Japan: 1997. R
  • 3 Takahashi K. Someya T. Muraki S. Yoshida T. Agric. Biol. Chem. 1980; 44: 1535
    • 4a Tsuboi SK. Shimozuma K. Takeda A. J. Org. Chem. 1980; 45: 1517
    • 4b Hirsch JA. Eastman RH. J. Org. Chem. 1967; 32: 2915
  • 5 Gao P. Xu PF. Zhai H. J. Org. Chem. 2009; 74: 2592
  • 6 Ferraz HM. C. Grazini MV. A. Ribeiro CM. R. Brocksom U. Brocksom TJ. J. Org. Chem. 2000; 65: 2606
    • 7a Shishido K. Irie O. Shibuya M. Tetrahedron Lett. 1992; 33: 4589
    • 7b Chavan SP. Zubaidha PK. Tetrahedron Lett. 1992; 33: 4605
    • 7c Crisp GT. Meyer AG. Tetrahedron 1995; 51: 5831
    • 7d Bates RW. Sridhar S. J. Org. Chem. 2008; 73: 8104
    • 7e Carda M. Marco JA. Tetrahedron Lett. 1991; 32: 5191
    • 7f Cory RM. Ritchie BM. Shrier AM. Tetrahedron Lett. 1990; 31: 6789
    • 7g Curini M. Epifano F. Marcotullio MC. Montanari F. Synlett 2004; 368
    • 7h Patel RM. Puranik VG. Argade NP. Org. Biomol. Chem. 2011; 9: 6312
    • 7i Chavan SP. Zubaidha PK. Dhondge VD. Tetrahedron 1993; 49: 6429
    • 7j Ferraz HM. Longo LS. Jr. Grazini MV. Synthesis 2002; 2155
  • 8 Bilel H. Hamdi N. Zagrouba F. Fischmeister C. Bruneau C. Green Chem. 2011; 13: 1448
  • 9 Preparation of (+)-Mintlactone (1) To the freshly made Sm powder (0.24 g, 1.6 mmol) was added THF (4.0 mL) and CH2I2 (0.40 g, 1.5 mmol) at the r.t. and the mixture was stirred for 40 min (the color of the solution turns to dark blue). Then to the solution was added t-BuOH (0.15 g, 2.0 mmol) at –20 °C. After stirring for 5 min, substrate 7 (0.1 g, 0.5 mmol) in anhydrous THF (1.0 mL) was added dropwise. After stirring for 2 h, sat. NH4Cl was added to quench the reaction. The organic layer was separated, and the aqueous layer was extracted with EtOAc (3 × 10 mL). The solvents were evaporated under reduced pressure, and the crude product was purified by flash column chromatography to yield 57 mg of the crude lactone product. 100 mg of crude lactone product was dissolved in anhydrous THF (2 mL), KHMDS (0.90 mL, 1 mmol/L in THF) was added at –78 °C. After stirring for 20 min, TMSCl (83 mg, 0.76 mmol) was added. To the resultant solution, NBS (139 mg, 0.78 mmol) in THF (2 mL) was added after a further 15 min. The reaction mixture was stirred at –78 °C for 4 h. And then sat. NH4Cl (1 mL) was added to quench the reaction. The organic layer was separated, and the aqueous layer was extracted with EtOAc (3 × 5 mL). The solvents and the crude bromolactone were evaporated under reduced pressure. To a solution of the crude bromolactone obtained above in toluene (4 mL), DBU (91 mg, 0.60 mmol) was added. The reaction mixture was refluxed for 90 min, and solvent was removed under reduced pressure to furnish a residue. Then the residue was purified with column chromatography to afford 1 (mixture of isomers, 67 mg, 68%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 4.60 (dd, J = 11.3, 6.1 Hz, 1 H), 2.77 (ddd, J = 14.2, 4.3, 1.8 Hz, 1 H), 2.45–2.36 (m, 1 H), 2.17 (td, J = 13.8, 5.6 Hz, 1 H), 1.99–1.88 (m, 1 H), 1.79 (d, J = 1.5 Hz, 3 H), 1.75–1.64 (m, 1 H), 1.06–0.93 (m, 5 H). 13C NMR (101 MHz, CDCl3): δ = 174.8, 162.3, 119.6, 79.9, 42.0, 34.6, 29.8, 25.5, 21.2, 8.2. ESI-HRMS: m/z calcd for C10H18NO2 [M + NH4]+: 184.1332; found: 184.1332.
  • 10 Kan T. Hosokawa S. Nara S. Tamiya H. Shirahama H. Matsuda F. J. Org. Chem. 2004; 69: 8956
    • 11a Ando K. J. Org. Chem. 1997; 62: 1934
    • 11b Nagaoka H. Kishi Y. Tetrahedron 1981; 37: 3873
  • 12 Preparation of (–)-Isomintlactone (2) The compound 12 was synthesized according to the procedures employed by the preparation of 8 to give the crude lactone product as a light yellow oil. 90 mg of crude lactone 12 was dissolved in anhydrous THF (2 mL), KHMDS (0.64 mL, 1.0 mmol/L in THF) was added at –78 °C. After stirring for 20 min, PhSeCl (134 mg, 0.70 mmol) in THF (2 mL) was added. The reaction mixture was stirred at –78 °C for 4 h. Then sat. NH4Cl (1 mL) was added to quench the reaction. The organic layer was separated, and the aqueous layer was extracted with EtOAc (3 × 5 mL). The solvents were evaporated under reduced pressure to give crude selenolactone. To the crude product dissolved in THF (4 mL), 30% H2O2 (0.1 mL) was added at 0 °C. After stirring for 3 min, the reaction was allowed to warm to r.t. to stir another 3 min. And then the reaction was quenched with aq Na2S2O3 and extracted with EtOAc (3 × 5 mL). The solvents were evaporated under reduced pressure, and the crude product was purified by flash column chromatography to yield 2 (mixture of isomers, 45 mg, 51%) as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ = 4.77 (dd, J = 11.0, 6.2 Hz, 1 H), 2.66 (ddd, J = 14.3, 4.6, 1.7 Hz, 1 H), 2.42–2.23 (m, 3 H), 1.79–1.77 (m, 4 H), 1.58–1.46 (m, 1 H), 1.33 (td, J = 12.0, 4.6 Hz, 1 H), 1.12 (d, J = 7.4 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ = 174.9, 163.0, 119.3, 77.4, 39.6, 31.7, 27.3, 21.8, 17.2, 8.1. ESI-HRMS: m/z calcd for C10H15O2 [M + H]+: 167.1067; found: 167.1067.
    • 13a Kimura T. Nakata T. Tetrahedron 2010; 21: 1389
    • 13b Hutton TK. Muir K. Procter DJ. Org. Lett. 2002; 4: 2345
    • 13c Hutton TK. Muir K. Procter DJ. Org. Lett. 2003; 25: 4811