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Synlett 2014; 25(08): 1160-1162
DOI: 10.1055/s-0033-1341059
letter
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (–)-HM-3 and (–)-HM-4 Utilizing a Palladium-Catalyzed Addition of an Arylboronic Acid to an Allenic Alcohol Followed by Eschenmoser–Claisen Rearrangement

Masahiro Yoshida*
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan   Fax: +81(88)6337294   Email: yoshi@tokushima-u.ac.jp
,
Tomoyo Kasai
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan   Fax: +81(88)6337294   Email: yoshi@tokushima-u.ac.jp
,
Tomotaka Mizuguchi
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan   Fax: +81(88)6337294   Email: yoshi@tokushima-u.ac.jp
,
Kosuke Namba
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan   Fax: +81(88)6337294   Email: yoshi@tokushima-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 14 February 2014

Accepted: 03 March 2014

Publication Date:
03 April 2014 (online)

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Abstract

The first asymmetric total synthesis of (–)-HM-3 and (–)-HM-4, aromatic sesquiterpenes isolated from the phytopathogenic fungus Helicobasidium mompa, has been achieved. Highlight of the synthesis is an enantiospecific construction of the quaternary carbon stereocenter utilizing a palladium-catalyzed addition of arylboronic acid to the allenic alcohol followed by Eschenmoser–Claisen rearrangement.

Key words

allenes - boron - Claisen rearrangement - natural products - palladium - total synthesis

Supporting 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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  • 7 To a stirred solution of allenic alcohol 5 (200 mg, 1.37 mmol) in dioxane–H2O (20:1; 13.7 mL) were added arylboronic acid 6 (537 mg, 2.74 mmol), Et3N (0.95 mL, 6.85 mmol), and [Pd2(OH)2(PPh3)4][BF4]2 (100.6 mg, 0.069 mmol) at r.t. After stirring was continued for 90 min at 80 °C, the reaction mixture was diluted with EtOAc and filtered through a pad of silica gel. The residue upon evaporation of the solvent was chromatographed on silica gel with hexane–EtOAc (95:5) as eluent to give allylic alcohol 7 as a mixture, which was used in the next reaction without further purification. To a stirred solution of allylic alcohol 7 (1.37 mmol) in p-xylene (29.1 mL) was added N,N-dimethyl-acetamide dimethylacetal (2.01 mL, 13.7 mmol) at r.t. After the stirring was continued under reflux conditions for 30 min, the solvent was removed in vacuo. The residue was chromatographed on silica gel with hexane–EtOAc (70:30) as eluent to give amide 4 (289.9 mg, 58% in 2 steps, 95% ee) as a yellow oil; [α]D 33 –9.6 (c = 1.00, CHCl3). IR (KBr): 3023, 2936, 1643, 1492, 1458, 1401, 1275, 1052, 1021 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.69 (s, 3 H), 2.24 (s, 3 H), 2.85 (s, 3 H), 2.93 (s, 3 H), 3.04 (d, J = 14.8 Hz, 1 H), 3.10 (d, J = 14.8 Hz, 1 H), 3.75 (s, 3 H), 3.77 (s, 3 H), 6.25 (d, J = 16.4 Hz, 1 H), 6.82 (d, J = 16.4 Hz, 1 H), 6.85 (d, J = 8.0 Hz, 1 H), 7.00 (d, J = 8.0 Hz, 1 H), 7.17 (t, J = 7.6 Hz, 1 H), 7.28 (t, J = 7.6 Hz, 2 H), 7.36 (d, J = 7.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 15.6 (Me), 26.4 (Me), 35.4 (Me), 37.7 (Me), 42.4 (CH2), 42.7 (Cq), 59.3 (Me), 60.0 (Me), 122.5 (CH), 124.7 (CH), 126.0 (CH), 126.0 (CH), 126.8 (CH), 128.4 (CH), 130.9 (Cq), 137.9 (Cq), 138.1 (Cq), 139.8 (CH), 151.6 (Cq), 151.7 (Cq), 171.3 (Cq). HRMS (ESI): m/z [M + H]+ calcd for C23H30NO3: 368.2226; found: 368.2226. Enantiomeric excess was determined by HPLC analysis [CHIRALCEL AS-H column, 10% isopropanol–hexane, flow rate = 0.3 mL/min, λ = 254 nm, t R = 24.6 min (S), t R = 26.6 min (R)].
  • 8 Data for 1: mp 137.8–140.5 °C (recrystallized from EtOAc–hexane); [α]D 29 –33.3 (c = 0.44, CHCl3). IR (KBr): 3339, 2924, 2361, 1736, 1421, 1373, 1281, 1239, 1191 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.74 (s, 3 H), 1.15 (s, 3 H), 1.40 (s, 3 H), 1.49–1.79 (m, 5 H), 2.11 (s, 3 H), 2.37 (s, 3 H), 2.53–2.61 (s, 1 H), 5.14 (s, 1 H), 6.69 (d, J = 8.0 Hz, 1 H), 7.08 (d, J = 8.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 16.0 (Me), 20.5 (CH2), 20.6 (Me), 22.9 (Me), 25.5 (Me), 26.9 (Me), 39.4 (CH2), 41.2 (CH2), 44.9 (Cq), 51.3 (Cq), 121.1 (CH), 126.3 (CH), 128.2 (Cq), 133.0 (Cq), 138.0 (Cq), 146.5 (Cq), 168.5 (Cq). HRMS (ESI): m/z [M + Na]+ calcd for C17H24O3Na: 299.1623; found: 299.1618.
  • 9 Data for 2: mp 104.5–106.9 °C (recrystallized from EtOAc–hexane); [α]D 33 –24.6 (c = 0.16, CHCl3). IR (KBr): 2926, 1715, 1507, 1457, 1373, 1294 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.76 (s, 3 H), 1.18 (s, 3 H), 1.41 (s, 3 H), 1.51–1.80 (m, 5 H), 2.22 (s, 3 H), 2.55–2.64 (m, 1 H), 4.88 (s, 1 H), 5.55 (s, 1 H), 6.59 (d, J = 8.4 Hz, 1 H), 6.79 (d, J = 8.4 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 15.2 (Me), 20.2 (CH2), 22.9 (Me), 25.3 (Me), 26.7 (Me), 39.2 (CH2), 40.9 (CH2), 44.9 (Cq), 51.0 (Cq), 120.6 (CH), 120.8 (CH), 121.1 (Cq), 131.2 (Cq), 142.1 (Cq), 143.1 (Cq). HRMS (ESI): m/z [M + Na]+ calcd for C15H22O2Na: 257.1517; found: 257.1516.
  • 10 1H NMR and 13C NMR spectral data of 1 and 2 were in complete agreement with those reported for the natural and synthetic products (ref. 1 and 2). Although the reason is not clear, the optical rotations of our synthetic samples were different from the values reported for the natural products1 [1: [α]D −8.1 (CHCl3); 2: [α]D −57.4 (CHCl3)].