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

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;

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

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References

References and Notes

For reviews regarding isolation, structure, and synthesis of pyranonaphthoquinone antibiotics, see:

<A NAME="RD02008ST-1A">1a</A> Brimble MA. Duncalf LJ. Nairn MR. Nat. Prod. Rep. 1999, 16: 267

<A NAME="RD02008ST-1B">1b</A> Brimble MA. Nairn MR. Prabaharan H. Tetrahedron 2000, 56: 1937

<A NAME="RD02008ST-1C">1c</A> Sperry J. Bachu P. Brimble MA. Nat. Prod. Rep. 2008, in press; DOI: 10.1039/b708811f

<A NAME="RD02008ST-2">2</A> Moore HW. Czerniak R. Med. Res. Rev. 1981, 1: 249

For racemic syntheses of dimeric pyranonaphthoquinones, see:

<A NAME="RD02008ST-3A">3a</A> Brimble MA. Duncalf LJ. Neville D. J. Chem. Soc., Perkin Trans. 1 1998, 4165

<A NAME="RD02008ST-3B">3b</A> Brimble MA. Lai MYH. Org. Biomol. Chem. 2003, 1: 4227

<A NAME="RD02008ST-3C">3c</A> Brimble MA. Lai MYH. Org. Biomol. Chem. 2003, 1: 2084

<A NAME="RD02008ST-3D">3d</A> For a racemic synthesis of cardinalin 3, see: Govender S. Mmutlane EM. van Otterlo WAL. de Koning CB. Org. Biomol. Chem. 2007, 5: 2433

<A NAME="RD02008ST-4A">4a</A> Gill M. Buchanan MS. Yu J. J. Chem. Soc., Perkin Trans. 1 1997, 919

<A NAME="RD02008ST-4B">4b</A> Gill M. Buchanan MS. Yu J. Aust. J. Chem. 1997, 50: 1081

<A NAME="RD02008ST-5">5</A> Gibson JS. Andrey O. Brimble MA. Synthesis 2007, 2611

<A NAME="RD02008ST-6">6</A> Kraus GA. Molina MT. Walling JA. J. Chem. Soc., Chem. Commun. 1986, 1568

<A NAME="RD02008ST-7A">7a</A> Hauser FM. Rhee RP. J. Org. Chem. 1978, 43: 178

<A NAME="RD02008ST-7B">7b</A> Kraus GA. Sugimoto H. Tetrahedron Lett. 1978, 19: 2263

For recent reviews on the Hauser-Kraus annulation, see:

<A NAME="RD02008ST-8A">8a</A> Rathwell K. Brimble MA. Synthesis 2007, 643

<A NAME="RD02008ST-8B">8b</A> Mal D. Pahari P. Chem. Rev. 2007, 107: 1892

<A NAME="RD02008ST-9">9</A> Andrey O. Sperry J. Larsen US. Brimble MA. Tetrahedron 2008, in press

<A NAME="RD02008ST-10A">10a</A> Denes B. Szantay C. Arch. Pharm. 1958, 342

<A NAME="RD02008ST-10B">10b</A> For a similar example employing molecular bromine, see: Abaev VT. Dmitriev AS. Gutnov AV. Podelyakin SA. Butin AV. J. Heterocycl. Chem. 2006, 43: 1195

<A NAME="RD02008ST-11">11</A> Brimble MA. Burgess CV. Synthesis 2007, 754

<A NAME="RD02008ST-12">12</A> Mill RJ. Taylor NJ. Snieckus V. J. Org. Chem. 1989, 54: 4372

<A NAME="RD02008ST-13">13</A> Nayak MK. Chakraborti AK. Tetrahedron Lett. 1997, 38: 8749

<A NAME="RD02008ST-14">14</A> Kaiser F. Schwink L. Velder J. Schmalz H.-H. J. Org. Chem. 2002, 67: 9248 ; and references therein

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.

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.

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.