Stereospecific Synthesis of Eight-Membered Polyhydroxy Carbocycles via TIBAL-Promoted Claisen Rearrangement

Abstract

The stereoselective synthesis of novel eight-membered polyhydroxy carbocycles was achieved from d-glucose via mercuriocyclization and triisobutylaluminum (TIBAL)-promoted Claisen rearrangement. Along with rearrangement, TIBAL also promoted debenzylation and cycloaddition, and a 3,9-dioxa-bicy­clo[3.3.1]nonane derivative was formed. The stereoselectivity of mercuriocyclization was attributed to the interaction between me­curio and vinyl moities, and this interaction also assisted the mercurio derivative to exist in an abnormal conformation. The configuration and/or conformation of intermediates and products were identified by NMR spectral analyses.

Key words

carbocycle - carbasugar - mercuriocyclization - TIBAL - Claisen rearrangement - debenzylation

References and Notes

• 1a Wani MC. Taylor HL. Wall ME. Coggon P. McPhail AT. J. Am. Chem. Soc.  1971,  93:  2325 
• 1b Magri NF. Kingston DGI. Jitrangsri C. Piccariello T. J. Org. Chem.  1986,  51:  3239 
• 1c Holton RA. Juo RR. Kim HB. Williams AD. Harusawa S. Lowenthal RE. Yogai S. J. Am. Chem. Soc.  1988,  110:  6558 
• 1d Chauviere G. Guenard D. Pascard C. Picot F. Potier P. Prange T. J. Chem. Soc., Chem. Commun.  1982,  495 
• 2 Fenical W. Shulte GR. Finer J. Clardy J. J. Org. Chem.  1978,  43:  3628 
• 3 Barrow KD. Barton DHR. Chain E. Ohnsorge UFW. Sharma RP. J. Chem. Soc., Perkin Trans. 1  1973,  1590 
• 4 Burke JW. Doskotch RW. Ni C.-Z. Clardy J. J. Am. Chem. Soc.  1989,  111:  5831 
• 5a Cope AC. Keough AH. Peterson PE. Simmons HE. Wood GW. J. Am. Chem. Soc.  1957,  79:  3900 
• 5b Cope AC. Fournier A. Simmons HE. J. Am. Chem. Soc.  1957,  79:  3905 
• 5c Kulkarni SU. Brown HC. J. Org. Chem.  1979,  44:  1747 
• 6a Shea KJ. Wise S. Tetrahedron Lett.  1979,  20:  1022 
• 6b Shea KJ. Wise S. Burke LD. Davis PD. Gilman JW. Greely AC. J. Am. Chem. Soc.  1982,  104:  5708 
• 6c Brown PA. Jenkins PR. J. Chem. Soc., Perkin Trans. 1  1986,  1303 
• 6d Sieburth SM. Chen J. Ravindran K. Chen J. J. Am. Chem. Soc.  1996,  118:  10803 
• 6e Sieburth SM. Siegel B. Chem. Commun.  1996,  2249 
• 7a Martin SF. White JB. Wagner R. J. Org. Chem.  1982,  47:  3190 
• 7b Snider BB. Allentoff AJ. J. Org. Chem.  1991,  56:  321 
• 8a Neh H. Blechert S. Schnick W. Jansen M. Angew. Chem. Int. Ed. Engl.  1984,  23:  905 
• 8b Blechert S. Kleine-Klausing A. Angew. Chem. Int. Ed. Engl.  1991,  30:  412 
• 8c Pradhan TK. Hassner A. Synlett  2007,  1071 
• 9 Kawada H. Iwamoto M. Utsugi M. Miyano M. Nakada M. Org. Lett.  2004,  6:  4491 
• 10 Michaut A. Rodriguez J. Angew. Chem. Int. Ed.  2006,  45:  5740 
• 11a Mehta G. Ramesh SS. Chem. Commun.  2000,  24:  2429 
• 11b Ogawa S. Funayama S. Okazaki K. Ishizuka F. Sakata Y. Doi F. Bioorg. Med. Chem. Lett.  2004,  14:  5183 
• 11c Grondal C. Enders D. Synlett  2006,  3507 
• 12a Das SK. Mallet J.-M. Sinaÿ P. Angew. Chem. Int. Ed. Engl.  1997,  36:  493 
• 12b Sollogoub M. Mallet J.-M. Sinaÿ P. Angew. Chem. Int. Ed.  2000,  39:  362 
• 12c Shing TKM. Cheng HM. J. Org. Chem.  2007,  72:  6610 
• 12d Shing TKM. Wong WF. Cheng HM. Kwok WS. So KH. Org. Lett.  2007,  9:  753 
• 13a Blériot Y. Giroult A. Mallet J.-M. Rodriguez E. Vogel P. Sinaÿ P. Tetrahedron: Asymmetry  2002,  13:  2553 
• 13b Liu Y. Han TX. Yang ZJ. Zhang LR. Zhang LH. Tetrahedron: Asymmetry  2007,  18:  2326 
• 13c Jia C. Zhang Y. Zhang L. Tetrahedron: Asymmetry  2003,  14:  2195 
• 13d Shing TKM. Wong AWF. Ikeno T. Yamada T. J. Org. Chem.  2006,  71:  3253 
• 13e Shing TKM. Wong AWF. Ikeno T. Yamada T. Org. Lett.  2007,  9:  207 
• 14 Liu PS. J. Org. Chem.  1987,  52:  4717 
• 15 Kapferer P. Sarabia F. Vasella A. Helv. Chim. Acta  1999,  82:  645 
• 17a Nicotra F. Ronchetti F. Russo G. J. Org. Chem.  1982,  47:  4459 
• 17b Nicotra F. Ronchetti F. Russo G. J. Chem. Soc., Chem. Commun.  1982,  470 
• 17c Nicotra F. Perego R. Ronchetti F. Russo G. Toma L. Carbohydr. Res.  1984,  131:  180 
• 17d Nicotra F. Panza L. Ronchetti F. Russo G. Toma L. Carbohydr. Res.  1987,  171:  49 

16

Synthesis of 7 To alkene 6 (1.30 g, 2.30 mmol) dissolved in anhyd THF (20 mL) was added Hg(OAc)₂ (0.73 g, 2.31 mmol) under argon. The reaction mixture was stirred and refluxed for 10 h, then sat. aq KCl (1 mL) was added, stirred, and refluxed for another 2 h, quenched by the addition of brine at r.t., and extracted three times with EtOAc. Organic extracts were combined, dried by Na₂SO₄, filtered, and evaporated. The residue was purified by column chromatography on SiO₂ (PE-EtOAc, 20:1) to give 7 as a colorless oil (1.85 g, 99.9%). ^¹H NMR (400 MHz, CDCl₃): δ = 7.33-7.18 (m, 20 H, arom. H), 5.96 (dd, J _7,8a = 11.0 Hz, J _7,8b = 17.5 Hz, 1 H, H-7), 5.23-5.27 (m, J _8a,7 = 11.0 Hz, J _8b,7 = 17.5 Hz, J _8a,8b = J _8b,8a = 1.5 Hz, 2 H, H-8a, H-8b), 4.66, 4.59 (dd, J = 11.5 Hz, 2 H, HCH₂Ph), 4.57, 4.51 (dd, J = 12.0 Hz, 2 H, HCH₂Ph), 4.35, 4.23 (dd, J = 12.0 Hz, 2 H, HCH₂Ph), 4.42 (m, J _2,3 = 3.0 Hz, J _2,1a = 6.0 Hz, J _2,1b = 4.0 Hz, 1 H, H-2), 3.90 (t, J _4,3 = 3.0 Hz, J _4,5 = 4.0 Hz, 1 H, H-4), 3.87, 3.41 (dd, J = 8.5 Hz, 2 H, H-9a, H-9b), 3.67 (d, J _5,4 = 4.0 Hz, 1 H,
H-5), 3.16 (t, J _3,2 = 3.0 Hz, J _3,4 = 3.0 Hz, 1 H, H-3), 1.94 (dd, J _1a,2 = 6.0 Hz, J _1a,1b = 12.0 Hz, 1 H, H-1a), 1.65 (dd, J _1b,2 = 4.0 Hz, J _1b,1a = 12.0 Hz, 1 H, H-1b). ^¹³C NMR (100 MHz, CDCl₃): δ = 139.2 (C-7), 138.5, 138.4, 138.0, 137.3 (4 × C_ipso), 129.1-127.5 (arom. C), 114.6 (C-8), 79.6 (C-6), 76.2 (C-3), 76.0 (C-5), 75.9 (C-9), 74.2 (C-4), 73.9, 73.7, 72.5, 72.1 (4 × CH₂Ph), 67.4 (C-2), 31.6 (C-1). MS (ESI-TOF⁺): m/z = 818 [M + NH₄]⁺, 823 [M + Na]⁺, 839 [M + K]⁺. Anal. Calcd for C₃₇H₃₉O₅HgCl: C, 55.57; H, 4.92. Found: C, 55.83; H, 5.10.

18

Synthesis of 9 Compound 8 (559 mg, 0.81mmol) dissolved in anhyd DMF (5 mL) was treated with NaH (60% in oil, 323 mg, 8.10 mmol) under argon. The reaction mixture was stirred for 1 h at r.t., quenched with MeOH, and concentrated. The residue was added H₂O and extracted with CH₂Cl₂. The organic extracts were washed twice with brine, dried by Na₂SO₄, filtered, and evaporated. The residue was purified by column chromatography (PE-EtOAc-Et₃N, 15:1:0.02) to yield 9 as a colorless oil (377 mg, 82.7%). ^¹H NMR (300 MHz, CDCl₃): δ = 7.02-6.78 (m, 20 H, arom. H), 5.88 (dd, J _7,8a = 17.5 Hz, J _7,8b = 11.0 Hz, 1 H, H-7), 5.43 (ss, J _8a,7 = 17.5 Hz, J _8a,8b = 1.5 Hz, 1 H, H-8a), 4.88 (dd, J _8b,7 = 17.5 Hz, J _8b,8a = 1.5 Hz, 1 H, H-8b), 4.70 (d, J _1a,1b = 1.5 Hz, 1 H, H-1a), 4.66 (d, J _1b,1a = 1.5 Hz, 1 H,
H-1b), 4.52 (dd, J = 11.5 Hz, 2 H, HCH₂Ph), 4.39 (dd, J = 11.5 Hz, 2 H, HCH₂Ph), 4.35 (dd, J = 11.5 Hz, 2 H, HCH₂Ph), 4.20 (dd, J = 11.5 Hz, 2 H, HCH₂Ph), 3.81 (m, J _5,4 = 8.0 Hz, J _4,5 = 8.0 Hz, J _4,3 = 8.0 Hz, 2 H, H-5, H-4), 3.58 (dd, J = 10.0 Hz, 2 H, H-9a, H-9b), 3.34 (d, J _3,4 = 8.0 Hz, 1 H, H-3). ^¹³C NMR (75 MHz, CDCl₃): δ = 156.0 (C-2), 139.3 (C-7), 139.0, 138.8, 138.7, 138.5 (4 × C_ipso), 128.6-127.7 (arom. C), 115.3 (C-8), 94.7 (C-1), 84.2 (C-6), 82.8 (C-3), 82.2 (C-5), 80.6 (C-4), 75.6 (C-9), 74.7, 73.9, 73.5, 71.1 (4 × CH₂Ph). MS (ESI-TOF⁺): m/z = 585 [M + Na]⁺, 601 [M + K]⁺. Anal. Calcd for C₃₇H₃₈O₅: C, 78.98; H, 6.81. Found: C, 78.80; H, 7.02.

19

Synthesis of 1
To the solution of compound 9 (660 mg, 1.17 mmol) in toluene (20 mL) was added dropwise 1 M TIBAL (11.7 mL, 11.7 mmol) in toluene at r.t. under argon. The mixture was stirred at 80 ˚C for 2 h, cooled to 0 ˚C, and quenched with 20% aq NaOH solution. The mixture was extracted with toluene, and the organic layers were combined, dried with Na₂SO₄, and concentrated. The residue was purified by column chromatography (PE-acetone, 20:1) to give 1 as colorless oil (571 mg, 86.5%). ^¹H NMR (300 MHz, CDCl₃): δ = 7.32-7.18 (m, 20 H, arom. H), 6.02 (t, J _6,7a = J _6,7b = 8 Hz, 1 H, H-6), 4.73 (d, J _4,3 = 6 Hz, 1 H, H-4), 4.61 (dd, J = 12 Hz, 2 H, HCH₂Ph), 4.58 (dd, J = 12 Hz, 2 H, HCH₂Ph), 4.48 (dd, J = 12 Hz, 2 H, HCH₂Ph), 4.33 (dd, J = 12 Hz, 2 H, HCH₂Ph), 4.11 (t, J _1,2 = 7 Hz, J _1,8a = 7 Hz, 1 H, H-1), 4.00 (dd, J = 12 Hz, 2 H, H-9), 3.90 (t, J _3,2 = J _3,4 = 6 Hz, 1 H,
H-3), 3.63 (dd, J _2,3 = 6 Hz, J _2,1 = 7 Hz, 1 H, H-2), 3.39 (s, 1 H, OH), 2.42 (br, 1 H, H-7a), 2.22 (br, 1 H, H-7b), 2.04 (t, J _8b,8a = 13 Hz, 1 H, H-8b), 1.71 (m, J _8a,8b = 13 Hz, J _8a,1 = 7 Hz, 1 H, H-8a). ^¹³C NMR (75 MHz, CDCl₃): δ = 138.6, 138.4, 138.1, 138.1 (4 × C_ipso), 134.2 (C-5), 131.4 (C-6), 128.4-127.4 (arom. C), 84.4 (C-3), 81.3 (C-2), 78.7 (C-4), 74.2, 72.5, 72.2, 71.2 (4 × CH₂Ph), 70.4 (C-1), 32.9 (C-8), 21.3 (C-7). MS (ESI-TOF⁺): m/z = 565 [M + H]⁺, 582 [M + NH₄]⁺, 587 [M + Na]⁺, 603 [M + K]^+. Anal. Calcd for C₃₇H₄₀O₅: C, 78.69; H, 7.14. Found: C, 78.84; H, 6.91.

20

Compound 10: white solid. ^¹H NMR (500 MHz, CDCl₃):
δ = 7.26-7.19 (m, 15 H, H-arom.), 5.74 (dd, J _10,11a = 18 Hz, J _10,11b = 11 Hz, 1 H, H-10), 5.26 (dd, J _11a,10 = 18 Hz, J _11a,11b = 2 Hz, 1 H, H-11a), 5.09 (dd, J _11b,10 = 11 Hz, J _11b,11a = 2 Hz, 1 H, H-11b), 4.87 (dd, J = 12 Hz, 2 H, HCH₂Ph), 4.82 (dd, J = 12 Hz, 2 H, HCH₂Ph), 4.66 (dd, J = 12 Hz, 2 H, HCH₂Ph), 4.58 (t, J _7,6 = J _7,8 = 9 Hz, 1 H,
H-7), 4.13 (d, J _2a,2b = 12 Hz, 1 H, H-2a), 4.02 (d, J _4a,4b = 12 Hz, 1 H, H-4a), 3.79 (dd, J _6,5 = 5 Hz, J _6,7 = 9 Hz, 1 H, H-6), 3.75 (dd, J _5,6 = 5 Hz, J _5,4b = 3 Hz, 1 H, H-5), 3.54 (dd, J _4b,4a = 12 Hz, J _4b,5 = 3 Hz 1 H, H-4b), 3.39 (d, J _8,7 = 9 Hz, 1 H, H-8), 3.22 (d, J _2b,2a = 12 Hz, 1 H, H-2b). ^¹³C NMR (125 MHz, CDCl₃): δ = 139.0, 138.6, 138.3 (3 × C_ipso), 136.8 (C-10), 128.4-127.4 (arom. C), 115.5 (C-11), 84.4 (C-8), 83.7 (C-7), 80.9 (C-6), 75.5, 75.3, 73.2 (3 × CH₂Ph), 74.6 (C-1), 69.6 (C-5), 68.8 (C-2), 63.8 (C-4). MS (ESI-TOF⁺): m/z = 490 [M + NH₄]⁺, 495 [M + Na]⁺, 511 [M + K]^+. Anal. Calcd for C₃₇H₄₀O₅: C, 76.25; H, 6.83. Found: C, 76.50; H, 7.05.

21

Synthesis of 2
To the solution of Ph₃P (296 mg, 1.13 mmol) in anhyd THF (3 mL) previously cooled in an ice bath was added dropwise 2.2 M DEAD in toluene (0.5 mL, 1.13 mmol) under argon. After 30 min, this solution was added dropwise to the solution of compound 1 (254 mg, 0.45 mmol) and benzoic acid (100 mg, 0.82 mmol) in anhyd THF under argon in an ice bath. The mixture was stirred for 30 min at 0 ˚C, then stirred at 45 ˚C for 3 h. When the volatiles were removed, the residue was purified by column chromatography (PE-acetone, 40:1) to yield 10 as colorless oil (290 mg, 96.5%). Compound 10 (362 mg, 0.54 mmol) dissolved in MeOH (10 mL) was treated with K₂CO₃ (372 mg, 2.69 mmol) and stirred at r.t. for 12 h. The reaction mixture was subsequently filtered and concentrated, and the residue was purified by column chromatography (PE-acetone, 20:1) to afford 2 as colorless oil (254 mg, 82.7%). ^¹H NMR (500 MHz, CDCl₃): δ = 7.31-7.21 (m, 20 H, arom. H), 6.03 (t, J _6,7a = J _6,7b = 8.5 Hz, 1 H, H-6), 4.67 (dd, J = 12.0 Hz, 2 H, HCH₂Ph), 4.62 (dd, J = 12.0 Hz, 2 H, HCH₂Ph), 4.47 (dd, J = 12.0 Hz, 2 H, HCH₂Ph), 4.43 (dd, J = 12.0 Hz, 2 H, HCH₂Ph), 4.41 (m, J _2,1 = 2.5 Hz, J _2,3 = 6.0 Hz, 1 H, H-2), 4.07-3.98 (m, 3 H,
H-1, H-9a, H-9b), 3.83 (t, J _3,2 = 6.0 Hz, J _3,4 = 5.0 Hz, 1 H,
H-3), 3.69 (d, J _4,3 = 5.0 Hz, 1 H, H-4), 2.36 (br, 1 H, H-7a), 2.10 (m, 1 H, H-7b), 2.00 (m, 1 H, H-8a), 1.70 (m, 1 H, H-8b). MS (ESI-TOF⁺): m/z = 565 [M + H]⁺, 582 [M + NH₄]⁺, 587 [M + Na]⁺, 603 [M + K]^+. Anal. Calcd for C₃₇H₄₀O₅: C, 78.69; H, 7.14. Found: C, 78.64; H, 7.02.