Synthesis of Dictyopterene A

Abstract

The total synthesis of dictyopterene A was accomplished via an enantiomerically pure cyclopropylboronic ester building block. Crucial olefination steps were carried out employing the Julia-Kocienski as well as the Wittig reactions. The Matteson homologation was the final key step for the total synthesis.

Key words

boron - cyclopropanes - natural products - total synthesis - stereoselectivity

References and Notes

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3

Later, (1S,2S)-dictyopterene B enantiomer was discovered us a minor component in female gametes and essential oils of families Scytosiphonaceae, Chordariaceae, Dictyo-taceae, see ref. 2m.

9

Thematic issue on cyclopropane chemistry (guest editor: A. de Meijere): Chem. Rev. 2002, 103, 931-1647.

16

Representative Procedure - Synthesis of E -olefin 6 To a stirred solution of the sulfone 7 (0.08 g, 0.28 mmol, 1.5 equiv) in anhyd DME (4 mL) at -60 °C under N₂ was added dropwise via cannula a solution of KHMDS (0.07 g, 0.34 mmol, 1.8 equiv) in anhyd DME (2 mL) over 5 min. The yellow-orange solution was stirred for 5 min and the aldehyde 3 (0.1 g, 0.19 mmol, 1 equiv) in anhyd DME (2 mL) was added dropwise via cannula over 5 min. The reaction mixture was stirred additional 10 min at -60 °C and was then quenched with H₂O (1 mL). The mixture was stirred vigorously whilst warming to r.t., diluted with Et₂O (4 mL) and H₂O (4 mL), and finally extracted with Et₂O (3 × 4 mL). The combined organic layers were dried (MgSO₄), filtered, and concentrated under reduced pressure. The crude product 6 was purified by flash column chromatography (SiO₂, petroleum ether-EtOAc, 95:5) to afford the E-olefin 6 (0.10 g, 93%) as colorless crystals; E/Z > 99:1. The minor Z-isomer 6 was only detected by 600 MHz ¹H NMR and was removed by a single recrystallization from pentane.
E-Olefin 6: [α]_D ²⁰ -79.7 (c 1.0, CHCl₃); mp 113 °C. Anal. Calcd for C₃₉H₄₃BO₄ (586.57): C, 79.86; H, 7.39. Found: C, 79.91; H, 7.31. MS-FAB (NBA + NaI): m/z (%) = 609 (<5) [M + Na⁺], 197 (100) [Ph₂COCH₃ ⁺], 167 (12) [Ph₂C⁺], 105 (10) [C₇H₅O⁺], 77 (6) [C₆H₅ ⁺]. IR (film): 3060, 3024, 2956, 2932, 2833, 1493, 1446, 1421, 1366, 1239, 1184, 1075, 1032, 1019, 965, 921, 857 cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = -0.53 (ddd, ³ J _{1 ′,3 ′b} = 9.8 Hz, ³ J _{1 ′,3 ′a} = 6.5 Hz, ³ J _{1 ′,2 ′} = 5.3 Hz, 1 H, 1′-H), 0.24 (ddd, ³ J _{2 ′,3a ′}= 7.8 Hz, ³ J _{1 ′,3 ′a} = 6.4 Hz, ³ J _{3 ′a,3 ′b} = 3.4 Hz, 1 H, 3′-H_a), 0.34 (ddd, ³ J _{1 ′,3 ′b} = 9.8 Hz, ³ J _{2 ′,3 ′b} = 6.5 Hz, ³ J _{3 ′a, 3 ′b} = 3.4 Hz, 1 H, 3′-H_b), 0.91 (t, ³ J _{5 ′′,6 ′′} = 7.2 Hz, 3 H, 6′′-H), 1.17-1.27 (m, 1 H, 2′-H), 1.28-1.36 (m, 4 H, 4′′-H, 5′′-H), 1.95 (m, 2 H, 3′′-H), 2.99 (s, 6 H, OCH₃), 4.79 (dd, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{1 ′′,2 ′} = 8.5 Hz, 1 H, 1′′-H), 5.25 (s, 2 H, 4-H, 5-H), 5.51 (dt, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{2 ′′,3 ′′} = 6.9 Hz, 1 H, 2′′-H), 7.27-7.34 (m, 20 H, arom. H). ¹³C NMR (125 MHz, CDCl₃): δ = 1.8 (C-1′), 12.4 (C-6′′), 13.8 (C-3′), 21.0 (C-5′′), 22.1 (C-4′′), 27.2 (C-2′), 31.8 (C-3′′), 51.7 (CPh₂OCH₃), 77.7 (C-4 and C-5), 83.3 (CPh₂OCH₃), 127.1, 127.2, 127.4, 127.7, 128.1, 128.3 (arom. CH), 129.6 (C-1′′), 133.5 (C-2′′), 141.1, 141.3 (arom. C_ipso).

21

(-)-(1S,2S)-Dictyopterene A (1): [α]_D ²⁰ -69.3 (c 0.40, CHCl₃); ref. 2d: [α]_D ²² +72 (c 6.74, CHCl₃) for the 1R,2R-enantiomer. GC-MS (EI, 70 eV): m/z (%) = 150 (100) [M⁺], 135 (15) [M⁺ - CH₃], 122 (24) [M - C₂H₄ ⁺], 121 (60) [M - C₂H₅ ⁺]. ¹H NMR (600 MHz, CDCl₃): δ = 0.75-0.84 (m, 2 H, 3′-H), 0.87 (t, ³ J _{5 ′′,6 ′′} = 7.0 Hz, 3 H, 6′′-H), 1.25-1.35 (m, 4 H, 4′′ and 5′′-H), 1.36-1.41 (m, 2 H, 1′-H and 2′-H), 1.95-2.05 (m, 2 H, 3′′-H), 4.84 (dd, ³ J _1,2 = 10.2 Hz, ² J _2a,2b = 2.3 Hz, 1 H, 2-H_a), 4.98 (dd, ³ J _1,2 = 17.2 Hz, ² J _2a,2b = 2.3 Hz, 1 H, 2-H_b), 5.03 (dd, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{1 ′′,2 ′} = 6.1 Hz, 1 H, 1′′-H), 5.36 (ddd, ³ J _1,2 = 10.2 Hz, ³ J _1,2 = 17.2 Hz, ³ J _{1,1 ′} = 6.7 Hz, 1 H, 1-H), 5.46 (dt, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{2 ′′,3 ′′} = 6.9 Hz, 1 H, 2′′-H). ¹³C NMR (150 MHz, CDCl₃): δ = 14.1 (C-6′′), 14.8 (C-3′), 22.3 (C-5′′), 23.6 (C-2′), 24.3 (C-1′), 31.8 (C-4′′), 32.2 (C-3′′), 111.8 (C-2), 129.2 (C-2′′), 131.6 (C-1′′), 140.9 (C-1).