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Synlett 2017; 28(08): 966-969
DOI: 10.1055/s-0036-1588940
letter
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Organocatalytic Michael/Michael/Henry Sequence to Construct Cyclohexanes with Six Vicinal Stereogenic Centers

Yushuang Chen
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: liuxh@scu.edu.cn
,
Xiaohua Liu*
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: liuxh@scu.edu.cn
,
Weiwei Luo
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: liuxh@scu.edu.cn
,
Lili Lin
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: liuxh@scu.edu.cn
,
Xiaoming Feng
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. of China   Email: liuxh@scu.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 18 November 2016

Accepted after revision: 31 December 2016

Publication Date:
30 January 2017 (online)

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Abstract

An efficient, asymmetric, catalytic, triple-cascade reaction between α-keto esters and nitroalkenes to construct cyclohexanes with six vicinal stereogenic centers in good yields and with high enantioselectivities has been established. A bifunctional guanidine–amide organocatalyst proved to be useful for the Michael/Michael/Henry sequence through Brønsted base and hydrogen-bonding cooperative catalysis.

Key words

asymmetric catalysis - cascade reaction - cyclohexanes - organocatalysis - keto esters - nitroalkenes
 

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  • 9 Hexasubstituted Cyclohexanes 3aa–3ik; General Procedure Guanidine G-5 (10 mol%), α-keto ester 1 (0.1 mmol), and 4 Å MS (20 mg) were weighed into a test tube under N2. THF (0.5 mL) was added and the solution was stirred for 0.5 h at 0 °C. Nitroalkene 2 (0.3 mmol) was then added at 0 °C, and the resulting mixture was stirred for 3 d at 0 °C to give the product 3, which was purified by flash chromatography.
  • 10 tert-Butyl (1R,2R,3R,4S,5R,6S)-2-Benzyl-1-hydroxy-4,6-dinitro-3,5-diphenylcyclohexanecarboxylate (3aa) White solid; yield: 51.7 mg (93%, 90% ee, >20:1 dr); mp 162 °C; [α]D 29 +45.3 (c 0.47, CH2Cl2); HPLC: [Daicel CHIRALCEL IA; hexane–i-PrOH (85:15); flow rate = 1.0 mL/min; λ = 210 nm]: t R = 7.33 min (minor), 12.59 min (major). 1H NMR (400 MHz, CDCl3): δ = 7.35–7.08 (m, 13 H), 6.78 (d, J = 7.2 Hz, 2 H), 5.22–5.16 (m, 1 H), 5.10 (dd, J = 12.4, 6.4 Hz, 1 H), 4.49 (t, J = 12.4 Hz, 1 H), 4.18 (s, 1 H), 3.54 (t, J = 6.4 Hz, 1 H), 2.95 (s, 1 H), 2.54–2.36 (m, 2 H), 1.59 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 171.5, 137.4, 134.9, 132.1, 129.0, 128.9, 128.6, 128.5, 128.4, 128.3 127.0, 92.7, 90.3, 86.6, 77.7, 47.1, 45.7, 40.3, 33.7, 27.9. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C30H32N2NaO7 +: 555.2102; found: 555.2101. tert-Butyl (1R,2R,3R,4S,5R,6S)-2-Benzyl-1-hydroxy-4,6-dinitro-3,5-bis(2-tolyl)cyclohexanecarboxylate (3ah) White solid; yield: 53.0 mg (91%, 95% ee, >20:1 dr); mp 140 °C; [α]D 26 +72.6 (c 1.26, CH2Cl2); HPLC: [Daicel CHIRALCEL IA; hexane–i-PrOH (85:15); flow rate = 1.0 mL/min; λ = 210 nm]: t R = 10.21 min (minor), 16.58 min (major). 1H NMR (400 MHz, CDCl3): δ = 8.53 (d, J = 7.6 Hz, 1 H), 7.33 (d, J = 7.6 Hz, 1 H), 7.24–7.08 (m, 8 H), 6.97 (d, J = 7.6 Hz, 1 H), 6.74 (d, J = 6.0 Hz, 2 H), 5.27 (t, J = 12.0 Hz, 2 H), 4.88 (t, J = 12.0 Hz, 1 H), 4.35 (s, 1 H), 4.16 (t, J = 6.4 Hz, 1 H), 3.26 (s, 1 H), 2.65–2.53 (m, 1 H), 2.50 (s, 3 H), 2.49–2.32 (m, 1 H), 1.64 (s, 9 H), 1.32 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 171.6, 140.0, 139.3, 137.0, 133.2, 131.7, 131.3, 131.2, 131.1, 129.0, 128.8, 128.1, 128.0, 126.9, 126.3, 126.2, 124.0, 93.1, 90.8, 86.5, 77.8, 45.2, 39.8, 34.8, 33.5, 27.9, 19.5, 19.3. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C32H36N2NaO7 + : 583.2415; found: 583.2415.