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Synlett 2014; 25(2): 288-292
DOI: 10.1055/s-0033-1340291
DOI: 10.1055/s-0033-1340291
letter
Asymmetric Total Synthesis of (–)-trans-Blechnic Acid via Rhodium(II)-Catalyzed C–H Insertion and Palladium(II)-Catalyzed C–H Olefination Reactions
Further Information
Publication History
Received: 19 September 2013
Accepted after revision: 22 October 2013
Publication Date:
03 December 2013 (online)
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Abstract
An asymmetric total synthesis of (–)-trans-blechnic acid, a dihydrobenzofuran neolignan, has been achieved. The key steps involve an elaboration of the cis-2,3-dihydrobenzofuran core structure by enantio- and diastereoselective intramolecular C–H insertion using dirhodium(II) tetrakis[N-phthaloyl-(R)-tert-leucinate] [Rh2(R-PTTL)4] and a direct coupling of an acrylate unit with the core structure employing Yu’s palladium(II)-catalyzed intermolecular C–H olefination.
Key words
chiral dirhodium(II) catalyst - C–H insertion - C–H olefination - dihydrobenzofuran neolignan - blechnic acidsSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
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- 27 Procedure for the Rh2(R-PTTL)4-Catalyzed Intramolecular C–H Insertion of Compound 13 Rh2(R-PTTL)4 (63.9 mg, 0.045 mmol, 1 mol%) was added to a stirred solution of 4 Å MS (3.20 g) and 13 (3.20 g, 4.49 mmol) in toluene (45 mL) at –20 °C. After stirring for 1 h, the reaction mixture was filtered through a Celite pad. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (silica gel; toluene–EtOAc, 200:1) to give 12 as a white solid (2.50 g, 81%); Rf = 0.56 (toluene–EtOAc, 100:1); mp 67.0–68.5 °C; [α]D 20 –10.5 (c 0.33, CHCl3). IR (neat): ν = 2945, 2867, 1744 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.03–1.09 (m, 36 H), 1.15–1.29 (m, 6 H), 3.51 (s, 3 H), 4.10 (ddt, J = 1.6, 6.0, 13.6 Hz, 1 H), 4.23 (ddt, J = 1.6, 6.0, 13.6 Hz, 1 H), 4.65 (d, J = 10.0 Hz, 1 H), 5.07 (d, J = 1.6 Hz, 1 H), 5.11 (dt, J = 1.6, 6.0 Hz, 1 H), 5.24 (s, 2 H), 5.52–5.62 (m, 1 H), 5.90 (d, J = 10.0 Hz, 1 H), 6.73 (s, 1 H), 6.74 (s, 1 H), 6.77 (s, 1 H), 6.88 (t, J = 7.6 Hz, 1 H), 6.96 (d, J = 7.6 Hz, 1 H), 7.07 (d, J = 7.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 13.1, 13.3, 18.0, 18.1, 54.0, 56.4, 65.6, 86.2, 95.6, 117.2, 118.1, 118.4, 119.4, 119.5, 119.8, 121.8, 126.3, 129.6, 131.9, 141.7, 146.7, 147.3, 149.8, 169.3. ESI-HRMS: m/z calcd for C38H60O7NaSi2 [M + Na]+: 707.3770; found: 707.3768. The ee of 12 was determined to be 80% by HPLC with a Chiralcel IF (hexane–iPrOH, 300:1, 0.5 mL/min): t R = 35.9 min for the major enantiomer, t R = 49.2 min for the minor enantiomer.
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- 31 Procedure for the Pd(II)-Catalyzed C–H Olefination of Compound 19b To a solution of 19b (340 mg, 0.566 mmol), Pd(OAc)2 (25 mg, 0.113 mmol, 20 mol%), KHCO3 (199 mg, 1.98 mmol), and Ac-Ile-OH (39 mg, 0.226 mmol, 40 mol%) in tert-amyl-OH (5 mL) was added a solution of trichloroethyl acrylate (129 mg, 0.633 mmol) in tert-amyl alcohol (1 mL) under O2 (1 atm, balloon). The reaction mixture was stirred for 8 h at 50 °C. The mixture was partitioned between EtOAc and 10% aq citric acid, and the aqueous layer was separated. The organic layer was washed with brine and dried over Na2SO4. Filtration and evaporation in vacuo furnished the crude product (510 mg), which was purified by column chromatography (silica gel; toluene–MeCN, 25:1) to give 11b (226 mg, 50%) as a pale yellow amorphous; Rf = 0.41 (hexane–EtOAc, 3:1); [α]D 20 –17.3 (c 0.98, CHCl3). IR (neat): ν = 2945, 2867, 1716, 1610 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.04–1.11 (m, 36 H), 1.23–1.31 (m, 6 H), 4.65 (d, J = 9.2 Hz, 1 H), 4.82 (s, 2 H), 5.94 (d, J = 9.2 Hz, 1 H), 6.36 (d, J = 16.0 Hz, 1 H), 6.82–6.86 (m, 2 H), 6.90–6.94 (m, 2 H), 7.21 (d, J = 8.4 Hz, 1 H), 7.67 (d, J = 16.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 13.0, 13.1, 18.1, 53.3, 74.2, 87.5, 95.2, 115.7, 117.3, 118.3, 119.0, 120.0, 121.9, 123.9, 126.7, 127.7, 142.9, 143.2, 147.1, 147.6, 147.7, 165.3, 171.2. ESI-HRMS: m/z calcd for C38H55Cl3O8NaSi2 [M + Na]+: 823.2420; found: 823.2413.
- 32 Data for Synthetic (–)-trans-Blechnic Acid (1) A colorless needle; Rf = 0.27 (hexane–EtOAc–AcOH, 1:2:0.3); mp 196.0–197.0 °C (H2O); [α]D 26 –27.2 (c 0.78, MeOH). 1H NMR (500 MHz, CD3OD): δ = 4.59 (d, J = 9.0 Hz, 1 H), 5.93 (d, J = 9.0 Hz, 1 H), 6.26 (d, J = 16.0 Hz, 1 H), 6.75 (d, J = 8.5 Hz, 1 H), 6.80 (d, J = 8.5 Hz, 1 H), 6.84 (dd, J = 2.0, 8.5 Hz, 1 H), 6.96 (d, J = 2.0 Hz, 1 H), 7.14 (d, J = 8.5 Hz, 1 H), 7.56 (d, J = 16.0 Hz, 1 H). 13C NMR (125 MHz, acetone-d 6): δ = 54.4, 87.7, 114.9, 115.5, 117.6, 117.9, 119.4, 122.1, 124.2, 129.0, 129.1, 142.4, 144.5, 145.4, 145.9, 149.0, 167.9, 170.9. ESI-HRMS: m/z calcd for C18H14O8Na [M + Na]+: 381.0634; found: 381.0621.
For reviews on stereoselective synthesis of neolignans, see:
For recent examples of asymmetric total synthesis of natural products containing 2-aryl-2,3-dihydrobenzofuran, see: