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Synlett 2016; 27(09): 1428-1432
DOI: 10.1055/s-0035-1561576
DOI: 10.1055/s-0035-1561576
letter
Efficient Synthesis of Anastrephin via the Allylic Substitution for Quaternary Carbon Construction
Further Information
Publication History
Received: 02 January 2016
Accepted after revision: 02 February 2016
Publication Date:
29 February 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201609/lookinside/thumbnails/st-2016-u0002-l_10-1055_s-0035-1561576-1.jpg)
Abstract
Lactone-moiety-attached 2-cyclohexylideneethyl picolinate was prepared through the OH-directed epoxidation (98% ds) of (R)-3-methylcyclohex-2-en-1-ol (99% ee), Horner–Wadsworth–Emmons olefination, conversion to the allylic moiety, and epoxide ring opening with Et2AlCH2CO2 t-Bu. The allylic substitution of the picolinate with Me2CuMgBr·MgBr2 furnished a quaternary carbon center with 92% ds. Finally, the lactonization of the product, the tert-butyl ester of the seco acid, under acidic conditions, afforded (–)-anastrephin.
Key words
anastrephin - quaternary carbon - asymmetric synthesis - allylic substitution - copper reagent - picolinateSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561576.
- Supporting Information
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References and Notes
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- 19 A solution of 5b (E/Z = 47:53, 284 mg, 0.76 mmol) in THF (2 mL) was added to a mixture of MeMgBr (0.97 M in THF, 2.60 mL, 2.52 mmol), CuBr·Me2S (235 mg, 1.14 mmol) and ZnI2 (392 mg, 1.23 mmol) in THF (1 mL) at –40 °C. The resulting mixture was warmed to r.t. and stirred overnight to afford olefin 6b (105 mg, 51%, 92% ds) after chromatographic purification. 1H NMR (400 MHz, CDCl3): δ = 1.00 (s, 3 H), 1.08 (s, 3 H), 1.27–1.35 (m, 1 H), 1.39–1.46 (m, 1 H), 1.45 (s, 9 H), 1.50–1.60 (m, 2 H), 1.73 (br s, 1 H), 1.77–1.86 (m, 2 H), 1.95 (dd, J = 6.0, 4.8 Hz, 1 H), 2.31 (dd, J = 16.4, 4.8 Hz, 1 H), 2.45 (dd, J = 16.4, 6.4 Hz, 1 H), 5.00 (dd, J = 17.6, 1.2 Hz, 1 H), 5.03 (dd, J = 11.2, 0.8 Hz, 1 H), 5.88 (ddd, J = 17.6, 11.2, 0.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 20.2 (–), 22.1 (+), 28.1 (+), 30.1 (+), 31.8 (–), 37.5 (–), 41.1 (–), 43.2 (–), 53.9 (+), 73.0 (–), 80.4 (–), 112.5 (–), 142.2 (+), 174.8 (–). The diastereoselectivity of 6b was determined by integration of the key signals in the 1H NMR [δ = 5.88 (ddd) for 6b and δ = 5.71 (dd) for the diastereomer].