Efficient Synthesis of Functionalized Anthraquinones by Domino Twofold Heck-6π-Electrocyclization Reactions of 2,3-Dibromonaphthoquinone

Abstract

Functionalized anthraquinones were prepared by domino ‘twofold Heck-6π-electrocyclization’ reactions of 2,3-dibromo­naphthoquinone.

Key Words

catalysis - palladium - Heck reaction - electrocyclization - naphtoquinones

References and Notes

• 1 Römpp Lexikon Naturstoffe   Steglich W. Fugmann B. Lang-Fugmann S. Thieme; Stuttgart: 1997. 
• 2 Review: Krohn K. Angew. Chem., Int. Ed. Engl.  1986,  25:  790 ; Angew. Chem. 1986, 98, 788
• 3 Ishiyama D. Futamata K. Futamata M. Kasuya O. Kamo S. J. Antibiot.  1998,  51:  1069 
• 4a El-Beih AA. Kawabata T. Koimaru K. Ohta T. Tsukamoto S. Chem. Pharm. Bull.  2007,  55:  1097 
• 4b Nguemeving JR. Azebaze AGB. Kuete V. Carly NNE. Beng VP. Meyer M. Blond A. Bodo B. Nkengfack AE. Phytochemistry  2006,  67:  1341 
• 4c Dhananjeyan MR. Milev YP. Kron MA. Nair MG. J. Med. Chem.  2005,  48:  2822 
• 4d Liu R. Zhu W. Zhang Y. Zhu T. Liu H. Fang Y. Gu Q. J. Antibiot.  2006,  59:  362 
• 4e Wu T.-S. Lin D.-M. Shi L.-S. Damu AG. Kuo P.-C. Kuo Y.-H. Chem. Pharm. Bull.  2003,  51:  948 
• 4f Feng Z.-M. Jiang J.-S. Wang Y.-H. Zhang P.-C. Chem. Pharm. Bull.  2005,  53:  1330 
• 4g Nicolaou KC. Yee HL. Piper JL. Papageorgiou CD. J. Am. Chem. Soc.  2007,  129:  4001 
• 4h El-Gamal AA. Takeya K. Itokawa H. Halim AF. Amer MM. Phytochemistry  1995,  40:  245 
• 5 Diaz F. Chai H.-B. Mi Q. Su B.-N. Vigo JS. Graham JG. Cabieses F. Farnsworth NR. Cordell GA. Pezzuto JM. Swanson SM. Kinghorn AD. J. Nat. Prod.  2004,  67:  352 
• 6 Review: Schröter S. Stock C. Bach T. Tetrahedron  2005,  61:  2245 
• 7a Dang TT. Dang TT. Ahmad R. Reinke H. Langer P. Tetrahedron Lett.  2008,  49:  1698 
• 7b Dang TT. Villinger A. Langer P. Adv. Synth. Catal.  2008,  350:  2109 
• 7c Hussain M. Nguyen TH. Langer P. Tetrahedron Lett.  2009,  50:  3929 
• 7d Tengho Toguem S.-M. Hussain M. Malik I. Villinger A. Langer P. Tetrahedron Lett.  2009,  50:  4962 
• 7e Dang TT. Dang TT. Rasool N. Villinger A. Langer P. Adv. Synth. Catal.  2009,  351:  1595 
• 8 Ullah I. Khera RA. Hussain M. Langer P. Tetrahedron Lett.  2009,  50:  4651 
• For reviews of domino reactions, see:
• 9a Tietze LF. Beifuss U. Angew. Chem., Int. Ed. Engl.  1993,  32:  131 ; Angew. Chem. 1993, 105, 137
• 9b Tietze LF. Chem. Rev.  1996,  96:  115 
• 10 De Meijere and co-workers reported twofold Heck reac­tions of 1,2-dibromocycloalk-1-enes and related substrates and subsequent 6π-electrocyclization: Voigt K. von Zezschwitz P. Rosauer K. Lansky A. Adams A. Reiser O. de Meijere A. Eur. J. Org. Chem.  1998,  1521 ; and references cited therein
• 11 Billingsley K. Buchwald SL. J. Am. Chem. Soc.  2007,  129:  3358 ; and references cited therein

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General Procedure for the Synthesis of 3a-q and 4a-q
In a pressure tube (glass bomb) a suspension of Pd(OAc)₂ (12 mg, 0.05 mmol, 5 mol%) and XPhos (48 mg, 0.10 mmol) in DMF (5 mL) was purged with argon and stirred at 20 ˚C to give a yellowish or brownish clear solution. To the stirred solution were added 1 (316 mg, 1.0 mmol), Et₃N (1.1 mL, 8.0 mmol), and the alkene 2a-q (2.5 equiv). The reaction mixture was stirred at 90 ˚C (for 3a-q) or 110 ˚C (for 4a-q) for 8 h. The solution was cooled to 20 ˚C, poured into H₂O and CH₂Cl₂ (25 mL each), and the organic and the aqueous layer were separated. The latter was extracted with CH₂Cl₂ (3 × 25 mL). The combined organic layers were washed with H₂O (3 × 20 mL), dried (Na₂SO₄), concentrated in vacuo, and the residue was purified by chromatography (flash silica gel, heptanes-EtOAc) to give 3a-q or 4a-q. Diisobutyl 9,10-Dioxo-9,10-dihydroanthracene-2,3-dicarboxylate (3d)
Starting with 1 (316 mg, 1.0 mmol), 3d was isolated as a violet highly viscous oil (338 mg, 83%). ^¹H NMR (300 MHz, CDCl₃): δ = 0.95 (d, 12 H, J = 6.7 Hz, 4 CH₃), 1.96-2.10 (m, 2 H, CH), 4.09 (d, J = 6.7 Hz, 2 CH₂O), 7.77-7.81 (m, 2 H, ArH), 8.27-8.30 (m, 2 H, ArH), 8.56 (s, 2 H, ArH). ^¹³C NMR (62 MHz, CDCl₃): δ = 19.1 (4 CH₃), 27.7 (2 CH), 72.4 (2 CH₂O), 127.6, 128.0 (2 CH), 133.3, 133.3 (2 C), 134.7 (2 CH), 137.0, 166.2 (2 CO), 181.7 (2 CO). IR (KBr): ν = 3071, 2959, 2929, 2873 (m), 1726, 1679 (s), 1637, 1616 (w)1591, 1521, 1469 (m), 1407, 1391, 1377, 1369, 1333 (w), 1248 (s), 1172, 1134, 1119, 1035, 955, 946, 795, 780 (m), 710 (s), 654, 574 (w) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 408 (100) [M]⁺, 296 (47), 278 (27), 277 (17), 252 (15), 236 (06), 102 (40). HRMS (ESI⁺): m/z calcd for C₂₄H₂₄O₆ [M]⁺: 408.15729; found: 408.15730.

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