A One-Pot Deprotection and Intramolecular Oxa-Michael Addition to Access Angular Trioxatriquinanes

Abstract

An efficient one-pot deprotection-oxa-Michael addition strategy has been used to synthesize a few trioxatriquinanes starting from commercially available sugars.

triquinane - RCM - allylic oxidation - deprotection

References and Notes

1a Mehta G. Srikrishna A. Chem. Rev.  1997,  97:  671 

1b Singh V. Thomas B. Tetrahedron  1998,  54:  3647 

For selected references in this area, see:

2a Harrington-Frost NM. Pattenden G. Tetrahedron Lett.  2000,  41:  403 

2b Watson FC. Kilburn JD. Tetrahedron Lett.  2000,  41:  10341 

2c Verma SK. Fleischer EB. Moore HW.
J. Org. Chem.  2000,  65:  8564 

3a Mehta G. Srikrishna A. Reddy AV. Nair MS. Tetrahedron  1981,  37:  4543 

3b Mehta G. Reddy AV. Murthy AN. Reddy DS. J. Chem. Soc., Chem. Commun.  1982,  540 

3c Mehta G. Reddy DS. Murthy AN.
J. Chem. Soc., Chem. Commun.  1983,  824 

3d Mehta G. Rao KS. J. Chem. Soc., Chem. Commun.  1985,  1464 

3e Mehta G. Murthy AN. Reddy DS. Reddy AV. J. Am. Chem. Soc.  1986,  108:  3443 

3f Mehta G. Rao KS. J. Am. Chem. Soc.  1986,  108:  8015 

3g Wender PA. Correia CRD. J. Am. Chem. Soc.  1987,  109:  2523 

3h Mehta G. Rao KS. J. Org. Chem.  1988,  53:  425 

4a Wender PA. Sigget L. Nuss JM. In Comprehensive Organic Synthesis   Vol. 5:  Pergamon Press; Oxford: 1991.  p.654 

4b De Keukeleire D. Aldrichimica Acta  1994,  27:  59 

5a Hext NM. Hansen J. Blake AJ. Hibbs DE. Hursthouse MB. Shishkin OV. Mascal M. J. Org. Chem.  1998,  63:  6016 

5b Li Y. Meng Y. Meng X. Li Z. Tetrahedron  2011,  67:  4002 

6a Yadav JS. Kumar PTK. Gadgil VR. Tetrahedron Lett.  1992,  33:  3687 

6b Clive DLJ. Cole DC. Tao Y. J. Org. Chem.  1994,  59:  1396 

6c Woltering TJ. Hoffmann HMR. Tetrahedron  1995,  51:  7389 

6d Singh V. Alam SQ. Bioorg. Med. Chem. Lett.  2000,  2517 

6e Ader TA. Champey CA. Kuznetsova LV. Li T. Lim Y.-H. Rucando D. Sieburth S. McN. Org. Lett.  2001,  3:  2165 

6f Gurjar MK. Ravindranadh SV. Kumar P. Chem. Commun.  2001,  917 

6g Singh V. Alam SQ. Praveena GD. Tetrahedron  2002,  58:  9729 

7a Huang J.-M. Yokoyama R. Yang C.-S. Fukuyama Y. Tetrahedron Lett.  2000,  41:  6111 

7b Huang J.-M. Yang C.-S. Tanaka M. Fukuyama Y. Tetrahedron  2001,  57:  4691 

8 Krasso AF. Binder M. Tamm Ch. Helv. Chim. Acta  1972,  55:  1352 

9 Pettit GR. Kasturi TR. Knight JC. Occolowitz J.
J. Org. Chem.  1970,  35:  1404 

10 Gui J. Wang D. Tian D. Angew. Chem. Int. Ed.  2011,  50:  7093 

11a Toyota M. Nishikawa Y. Motoki K. Yoshida N. Fukumoto K. Tetrahedron Lett.  1993,  34:  6099 

11b Toyota M. Nishikawa Y. Motoki K. Yoshida N. Fukumoto K. Tetrahedron  1993,  49:  11189 

12a Kaliappan KP. Nandurdikar RS. Chem. Commun.  2004,  2506 

12b Kaliappan KP. Nandurdikar RS. Shaikh MM. Tetrahedron  2006,  62:  5064 

13a Smith MJ. Mazzola EP. Sims JJ. Midland SL. Keen NT. Burton V. Stayton MM. Tetrahedron Lett.  1993,  34:  223 

13b Midland SL. Keen NT. Sims JJ. Midland MM. Stayton MM. Burton V. Smith MJ. Mazzola EP. Graham KJ. Clardy J. J. Org. Chem.  1993,  58:  2940 

14 Nielsen P. Pfundheller HM. Olsen CE. Wengel J.
J. Chem. Soc., Perkin Trans. 1  1997,  3423 

15a Fu GC. Nguyen ST. Grubbs RH. J. Am. Chem. Soc.  1993,  115:  9856 

For some recent reviews related to RCM reactions, see:

15b Grubbs RH. Trnka TM. Acc. Chem. Res.  2001,  34:  18 

15c Deiters A. Martin SF. Chem. Rev.  2004,  104:  2199 

16a Fürstner A. Langemann K. J. Am. Chem. Soc.  1997,  119:  9130 

16b Ghosh AK. Cappiello J. Shin D. Tetrahedron Lett.  1998,  39:  4651 

16c Cossy J. Bauer D. Bellosta V. Tetrahedron Lett.  1999,  40:  4187 

17 Kaliappan KP. Kumar N. Tetrahedron Lett.  2003,  44:  379 

18

A 60% oil dispersion of NaH (75 mg, 1.84 mmol, 3 equiv), after washing with anhyd hexanes (3 × 5 mL), was suspended in anhyd THF (5 mL), and the reaction mixture was cooled to 0 ˚C. To this, a solution of compound 16 (280 mg, 0.61 mmol, 1 equiv) in anhyd THF (5 mL) was added dropwise and allowed to stir at r.t. for 1 h. Allyl bromide (0.1 mL, 1.23 mmol, 2 equiv) and TBAI (cat.) were added to the mixture at 0 ˚C, which was further stirred for 1 h at r.t. followed by heating to reflux for 4 h. The mixture was quenched by the careful addition of sat. aq NH₄Cl and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried over Na₂SO₄ and concentrated in vacuo to give the crude product. Silica gel column chromatography of the residue, eluting with 4% EtOAc in hexanes provided 22 (230 mg, 76%) as a colorless syrup. R _f  = 0.45 (10% EtOAc in hexanes); [α]_D ^²0 28.9 (c 1.14, CHCl₃). ^¹H NMR (400 MHz, CDCl₃): δ = 7.70-7.67 (m, 4 H), 7.42-7.33 (m, 6 H), 5.94-5.85 (m, 1 H), 5.81 (d, J = 3.6 Hz, 1 H), 5.58 (dd, J = 17.8, 11.3 Hz, 1 H), 5.25 (dd, J = 11.3, 0.9 Hz, 1 H), 5.23 (dq, J = 17.2, 1.8 Hz, 1 H), 5.16 (dd, J = 17.8, 0.9 Hz, 1 H), 5.11 (dq, J = 10.4, 1.5 Hz, 1 H), 4.45 (d, J = 3.6 Hz, 1 H), 4.33 (dd, J = 7.1, 3.5 Hz, 1 H), 4.10 (ddt, J = 12.4, 5.1, 1.6 Hz, 1 H), 3.98 (ddt, J = 12.4, 5.3, 1.6 Hz, 1 H), 3.78 (dd, J = 11.4, 3.5 Hz, 1 H), 3.70 (dd, J = 11.4, 7.2 Hz, 1 H), 1.61 (s, 3 H), 1.36 (s, 3 H), 1.03 (s, 9 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 135.9, 135.8, 135.1, 134.6, 133.8, 133.7, 129.7, 129.6, 127.8, 127.7, 117.9, 116.0, 112.9, 104.5, 84.9, 82.8, 81.8, 66.3, 63.5, 27.2, 27.0, 26.9, 19.4. IR (neat): ν = 3072, 2932, 2858, 1646, 1462, 1428, 1383, 1217, 1121, 1042, 927, 878, 823, 758, 704, 612, 548, 505 cm^-¹. ESI-HRMS: m/z calcd for C₂₉H₃₈O₅SiNa [M + Na]⁺: 517.2386; found: 517.2380.

19

To a solution of diene 22 (210 mg, 0.42 mmol, 1 equiv) in argon-purged CH₂Cl₂ was added Grubbs first-generation catalyst (5 mol%), and the mixture was refluxed for 12 h. DMSO (2-3 drops) was added and the mixture stirred for
6 h to remove metal impurities. The mixture was then concentrated in vacuo to give a residue which, upon purification by silica gel column chromatography with 14% EtOAc in hexane, afforded compound 23 (180 mg, 91%) as a colorless syrup. R _f  = 0.26 (16% EtOAc in hexanes); [α]_D ^²0 +27.6 (c 1.56, CHCl₃). ^¹H NMR (400 MHz, CDCl₃): δ = 7.69-7.65 (m, 4 H), 7.43-7.34 (m, 6 H), 5.98 (dt, J = 6.2, 1.3 Hz, 1 H), 5.80 (d, J = 3.6 Hz, 1 H), 5.67 (dt, J = 6.2, 1.5 Hz, 1 H), 4.69 (ddd, J = 13.4, 2.5, 1.7 Hz, 1 H) 4.57 (ddd, J = 13.4, 2.4, 1.7 Hz, 1 H), 4.32 (t, J = 4.5 Hz, 1 H), 4.22 (d, J = 3.7 Hz, 1 H), 3.68, 3.64 (ABq, J _AB = 11.4 Hz, 1 H), 3.66, 3.63 (ABq, J _AB = 11.4 Hz, 1 H), 1.63 (s, 3 H), 1.36 (s, 3 H), 1.03 (s, 9 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 135.9, 135.8, 133.6, 133.5, 129.8, 129.6, 127.8, 125.6, 113.2, 103.5, 95.8, 83.0, 80.4, 75.9, 63.0, 27.0, 26.9, 26.6, 19.3. IR (neat): ν = 3019, 2930, 2857, 1597, 1216, 1113, 1082, 1042, 758, 668 cm^-¹. ESI-HRMS: m/z calcd for C₂₇H₃₄O₅SiNa [M + Na]⁺: 489.2073; found: 489.2081.

20 Chidambaram N. Chandrasekaran S. J. Org. Chem.  1987,  52:  5048 

21

To a solution of spiroether 23 (260 mg, 0.56 mmol, 1 equiv) in benzene (20 mL) was added Celite (1.2 g/mmol) at r.t. and the mixture cooled to 0-10 ˚C. To this reaction mixture was added PDC (1.06 g, 2.8 mmol, 5 equiv), followed by t-BuOOH (0.39 mL, 2.8 mmol, 5 equiv), and the whole was stirred for 8 h at r.t. The reaction mixture was filtered through a pad of Celite and washed with EtOAc, the filtrate was concentrated in vacuo to furnish the crude product as a yellow syrup. Silica gel column chromatography, eluting with 20% EtOAc in hexanes afforded the spirolactone 21 (230 mg) as a colorless syrup in 85% yield. R _f  = 0.39 (40% EtOAc in hexanes); [α]_D ^²0 +52.2 (c 1.41, CHCl₃). ^¹H NMR (400 MHz, CDCl₃): δ = 7.66-7.59 (m, 4 H), 7.53 (d, J = 5.7 Hz, 1 H), 7.46-7.36 (m, 6 H), 6.14 (d, J = 5.7 Hz, 1 H), 5.98 (d, J = 3.7 Hz, 1 H), 4.52 (t, J = 3.7 Hz, 1 H), 4.49 (d, J = 3.7 Hz, 1 H), 3.73 (dd, J = 11.9, 4.1 Hz, 1 H), 3.61 (dd, J = 11.9, 3.6 Hz, 1 H), 1.63 (s, 3 H), 1.36 (s, 3 H), 1.03 (s, 9 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 170.9, 153.8, 135.7, 135.6, 132.7, 132.6, 130.1, 130.0, 128.0, 127.9, 121.3, 114.3, 103.5, 91.4, 81.6, 79.2, 61.0, 26.9, 26.8, 26.7, 19.3. IR (neat): ν = 3021, 2933, 2860, 1774, 1601, 1216, 1166, 1106, 1013, 759, 670 cm^-¹. ESI-HRMS: m/z calcd for C₂₇H₃₂O₆SiNa [M + Na]⁺: 503.1866; found: 503.1879.

22

To a solution of spirolactone 21 (270 mg, 0.56 mmol, 1 equiv) in anhyd THF (6 mL) was added TBAF solution in THF (1 M, 1.12 mL, 2 equiv) at 0 ˚C, and the mixture was stirred at the same temperature for 1 h. The reaction mixture was diluted with EtOAc, and solvents were removed in vacuo to obtain the crude product, which was purified by silica gel chromatography, eluting with 32% EtOAc in hexanes to afford the trioxatriquinane 12 (80 mg) as a white low-melting solid in 60% yield. R _f  = 0.19 (40% EtOAc in hexanes); [α]_D ^²0 +27.8 (c 1.29, CHCl₃). ^¹H NMR (400 MHz, CDCl₃): δ = 5.99 (d, J = 3.6 Hz, 1 H), 4.82 (d, J = 2.9 Hz, 1 H), 4.59 (d, J = 3.6 Hz, 1 H), 4.55 (dd, J = 6.7, 1.3 Hz, 1 H), 4.13 (d, J = 11.0 Hz, 1 H), 4.03 (dd, J = 11.0, 2.9 Hz, 1 H), 2.88 (dd, J = 19.0, 6.7 Hz, 1 H), 2.74 (dd, J = 19.0, 1.3 Hz, 1 H), 1.63 (s, 3 H), 1.39 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 173.6, 114.6, 105.9, 97.7, 83.0, 79.6, 79.2, 72.3, 35.5, 27.2, 27.0. IR (neat): ν = 3021, 2937, 1799, 1731, 1376, 1217, 1106, 1012, 909, 870, 758, 712, 669 cm^-¹. ESI-HRMS: m/z calcd for C₁₁H₁₄O₆Na [M + Na]⁺: 265.0688; found: 265.0682.

23 Mukai C. Moharram SM. Azukizawa S. Hanaoka M. J. Org. Chem.  1997,  62:  8095 

24 Nielsen P. Petersen M. Jacobsen JP. J. Chem. Soc., Perkin Trans. 1  2000,  3706