A Facile Enantioselective Synthesis of the Dimeric Pyranonaphthoquinone Core of the Cardinalins

Margaret A. Brimble; Jennifer S. Gibson; Jimmy J. P. Sejberg; Jonathan Sperry

doi:10.1055/s-2008-1042896

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Synlett 2008(6): 867-870
DOI: 10.1055/s-2008-1042896

LETTER

A Facile Enantioselective Synthesis of the Dimeric Pyranonaphthoquinone Core of the Cardinalins

Margaret A. Brimble*, Jennifer S. Gibson, Jimmy J. P. Sejberg, Jonathan Sperry
Department of Chemistry, University of Auckland, 23 Symonds Street, Auckland 1142, New Zealand
Fax: +64(9)3737422; e-Mail: m.brimble@auckland.ac.nz;

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Publication History

Received 11 January 2008
Publication Date:
11 March 2008 (online)

Abstract
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Abstract

The enantioselective synthesis of a dimeric pyranonaphthoquinone closely related to cardinalin 3 is described. Key steps include the Hauser-Kraus annulation between a cyanophthalide and a chiral enone to create the naphthalene skeleton, a Suzuki-Miyaura homocoupling of an aryl triflate to construct the biaryl bond and a double stereoselective lactol reduction to install the 1,3-cis stereochemistry of the pyran rings.

Key words

cardinalin - pyranonaphthoquinone antibiotics - Hauser-Kraus annulation - homocoupling

References and Notes

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15

Compound 9: colorless oil; [α]_D ²⁵ -21.8 (c 2.5, CH₂Cl₂); IR (oil): ν_max = 3070, 3049, 2959, 2932, 2894, 1679, 1588, 1450, 1427, 1348, 1330, 1204, 1112 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.97 [18 H, s, 2 × C(CH₃)₃], 0.98 (6 H, d, ³ J _HH = 6.0 Hz, 2 × CH₃), 2.48 (6 H, s, 2 × C=OCH₃), 2.90 (2 H, dd, ² J _HH = 13.4 Hz, ³ J _HH = 7.5 Hz, 2 × CHH), 3.11 (2 H, dd, ² J _HH = 13.4 Hz, ³ J _HH = 6.7 Hz, 2 × CHH), 3.81 (6 H, s, 2 × OCH₃), 3.90 (6 H, s, 2 × OCH₃), 4.27 [2 H, ddq (app. sext), ³ J _HH = 7.5, 6.7, 6.0 Hz, 2 × CH], 7.27 (4 H, m, ArH), 7.38 (8 H, m, ArH), 7.54 (4 H, dd, J = 8.1, 1.3 Hz, ArH), 7.66 (4 H, dd, J = 8.1, 1.6 Hz, ArH), 7.93 (2 H, dd, J = 8.8, 1.8 Hz, ArH), 8.15 (2 H, d, J = 8.8 Hz, ArH), 8.36 (2 H, d, J = 1.8 Hz, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 19.1 {2 × Si[C(CH₃)₃]}, 23.4 (2 × CHCH₃), 27.0 {2 × Si[C(CH₃)₃]}, 32.8 (2 × C=OCH₃), 37.0 (2 × CH₂), 61.8 (2 × OCH₃), 63.7 (2 × OCH₃), 69.6 (2 × CH), 120.6 (2 × CH_arom), 123.7 (2 × CH_arom), 124.8 (2 × C_arom), 126.8 (2 × CH_arom), 127.4 (8 × CH_arom), 127.9 (2 × C_arom), 128.3 (2 × C_arom), 129.40 (2 × CH_arom), 129.43 (2 × CH_arom), 134.27 (2 × C_arom), 134.31 (2 × C_arom), 134.7 (2 × C_arom), 135.8 (4 × CH_arom), 135.9 (4 × CH_arom), 138.6 (2 × C_arom), 149.3 (2 × C_arom), 151.6 (2 × C_arom), 205.3 (2 × C=O). MS-FAB: m/z (%) = 1050 (4) [M]⁺, 993 (6) [M - C(CH₃)₃]⁺, 795 (14), 397 (10), 197 (40), 135 (100). HRMS-FAB: m/z calcd for C₆₆H₇₄O₈Si₂ [M]⁺: 1050.4922; found: 1050.4921.

16

Compound 11: cream-colored solid; mp 268-269 °C; [α]_D ²⁴ +36.2 (c 0.12, CH₂Cl₂). IR (CH₂Cl₂): ν_max = 3418, 3053, 2986, 1638, 1421, 1264, 733 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.44 (6 H, d, ³ J _HH = 6.0 Hz, 2 × CHCH ₃), 1.73 (6 H, d, ³ J _HH = 6.6 Hz, 2 × CHCH ₃), 2.66 (2 H, dd, ² J _HH = 16.2 Hz, ³ J _HH = 11.0 Hz, 2 × CHH), 3.11 (2 H, dd, ² J _HH = 16.2 Hz, ³ J _HH = 1.5 Hz, 2 × CHH), 3.74 (2 H, m, 2 × CHCH₃), 3.91 (6 H, s, 2 × OCH₃), 3.95 (6 H, s, 2 × OCH₃), 5.26 (2 H, q, ³ J _HH = 6.6 Hz, 2 × CHCH₃), 7.89 (2 H, dd, ³ J _HH = 8.8 Hz, ⁴ J _HH = 1.6 Hz, ArH), 8.18 (2 H, d, ³ J _HH = 8.8 Hz, ArH), 8.37 (2 H, d, ⁴ J _HH = 1.6 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃): δ = 21.8 (2 × CHCH₃), 22.4 (2 × CHCH₃), 32.0 (2 × CH₂), 61.1 (2 × OCH₃), 61.4 (2 × OCH₃), 69.6 (2 × CH), 71.3 (2 × CH), 120.4 (2 × CH_arom), 122.8 (2 × CH_arom), 125.5 (2 × C_arom), 125.7 (2 × CH_arom), 126.6 (2 × C_arom), 127.7 (2 × C_arom), 129.9 (2 × C_arom), 138.3 (2 × C_arom), 148.8 (2 × C_arom), 149.0 (2 × C_arom). MS (EI): m/z (%) = 542 (100) [M]⁺, 527 (39), 199 (22), 105 (32), 57 (40), 44 (72). HRMS (EI): m/z calcd for C₃₄H₃₈O₆ [M]⁺: 542.2668; found: 542.2667.

17

Compound 1: yellow solid; mp 239-240 °C; [α]_D ²³ +356.1 (c 0.15, CH₂Cl₂). IR (CH₂Cl₂): ν_max = 3432, 3025, 1663, 1265, 736, 705 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.40 (6 H, d, ³ J _HH = 6.1 Hz, 2 × CHCH ₃), 1.58 (6 H, d, ³ J _HH = 6.5 Hz, 2 × CHCH ₃), 2.31 (2 H, ddd, J _HH = 18.7, 10.2, 4.0 Hz, 2 × CH _axH), 2.82 (2 H, dt, J _HH = 18.7, 2.5 Hz, 2 × CH _eqH), 3.64 (2 H, m, 2 × CHCH₃), 4.89 (2 H, m, 2 × CHCH₃), 8.02 (2 H, dd, ³ J _HH = 8.0 Hz, ⁴ J _HH = 1.9 Hz, ArH), 8.20 (2 H, d, ³ J _HH = 8.0, ArH), 8.35 (2 H, ⁴ J _HH = 1.9 Hz, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 20.8 (2 × CHCH₃), 21.2 (2 × CHCH₃), 30.5 (2 × CH₂), 68.7 (2 × CH), 70.0 (2 × CH), 125.0 (2 × CH_arom), 127.3 (2 × CH_arom), 131.4 (2 × CH_arom), 131.9 (2 × C_arom), 133.0 (2 × C_arom), 143.0 (2 × C_arom), 144.2 (2 × C_arom), 147.0 (2 × C_arom), 183.4 (2 × C=O), 183.7 (2 × C=O). MS (EI): m/z (%) = 482 (100) [M]⁺, 467 (20), 237 (15), 199 (20), 131 (21), 91 (99), 77 (25), 57 (37), 40 (85). HRMS (EI): m/z calcd for C₃₀H₂₆O₆ [M]⁺: 482.1729; found: 482.1720.