Thieme Chemistry Journal Awardees- Where are They Now? An Asymmetric Organocatalytic Sequence towards 4a-Methyl Tetrahydroxanthones: Formal Synthesis of 4-Dehydroxydiversonol

Abstract

Tricyclic systems generated by an asymmetric vinylogous aldol-oxa-Michael reaction of salicylaldehydes with seneci­aldehyde were further elaborated using a strategy developed by Tietze et al. to generate 4a-methyl tetrahydroxanthones.

Key words

domino vinylogous aldol-oxa-Michael reaction - ­Wittig reaction - natural products

References and Notes

• For organocatalytic domino reactions:
• 1a Enders D. Grondal C. Hüttl MM. Angew. Chem. Int. Ed.  2007,  46:  1570;   Angew. Chem.  2007,  119:  1590 
• 1b For organocatalytic conjugate addition reactions, see: Almasi D. Alonso DA. Najera C. Tetrahedron: Asymmetry  2007,  18:  299 
• 1c The use of salicylaldehyde in domino oxa-Michael reactions for the synthesis of chromenes, coumarins, and related heterocycles has already been reviewed: Shi Y.-L. Shi M. Org. Biomol. Chem.  2007,  5:  1499 
• 2a Lesch B. Toräng J. Vanderheiden S. Bräse S. Adv. Synth. Catal.  2005,  347:  555 
• 2b Gérard EMC. Sahin H. Encinas A. Bräse S. Synlett  2008,  2702 
• 2c Rao TV. Rele DN. Trivedi GK. J. Chem. Res.  1987,  196 
• 2d Lesch B. Toräng J. Nieger M. Bräse S. Synthesis  2005,  1888 
• 2e Nising CF. Bräse S. Chem. Soc. Rev.  2008,  37:  1218 
• 3 Liu K. Chougnet A. Woggon W.-D. Angew. Chem. Int. Ed.  2008,  47:  5827 ; Angew. Chem. 2008, 120, 5911
• 4 Tietze LF. Stecker F. Zinngrebe J. Sommer KM. Chem. Eur. J.  2006,  12:  8770 
• 5 Tietze LF. Spiegl DA. Stecker F. Major J. Raith C. Große C. Chem. Eur. J.  2008,  14:  8956 
• For a different approach to diversonol, see:
• 6a Nising CF. Ohnemüller UK. Bräse S. Angew. Chem. Int. Ed.  2006,  45:  307 ; Angew. Chem. 2006, 118, 313
• 6b Nicolaou KC. Li A. Angew. Chem. Int. Ed.  2008,  47:  6579;   Angew. Chem. 2008, 120, 6681
• The Trost group used also an asymmetric catalytic approach towards chromanes. The key step is a palladium-catalyzed etherification of phenols with allylic substrates to yield a tetrasubstituted stereogenic center and subsequent ring closure:
• 7a Trost BM. Toste FD. J. Am. Chem. Soc.  1998,  120:  9074 
• 7b Trost BM. Shen HC. Dong L. Surivet J.-P. J. Am. Chem. Soc.  2003,  125:  9276 
• 7c Trost BM. Shen HC. Dong L. Surivet J.-P. Sylvain C.
  J. Am. Chem. Soc.  2004,  126:  11966 
• 9 Franzén J. Marigo M. Fielenbach D. Wabnitz TC. Kjærsgaard A. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  18296 
• For the hydrogenation of benzylic alcohols, see:
• 10a Suzuki M. Kimura Y. Terashima S. Bull. Chem. Soc. Jpn.  1986,  59:  3559 
• 10b Orsini F. Sello G. Travaini E. Di Gennaro P. Tetrahedron: Asymmetry  2002,  13:  253 
• 10c Couche E. Fkyerat A. Tabacchi R. Helv. Chim. Acta  2003,  86:  210 
• 10d Kolarovic A. Berkes D. Baran P. Povazanec F. Tetrahedron Lett.  2005,  46:  975 
• Other Dieckmann condensations generating a 6-6 ring system:
• 12a Fu X. Pechacek JT. Smith DL. Wheeler DMS. Nat. Prod. Lett.  1992,  1:  213 
• 12b Hill CL. McGrath M. Hunt T. Grogan G. Synlett  2006,  309 
• 12c Stetter H. Heidel H. Chem. Ber.  1966,  99:  2172 
• 13 Sheldrick GM. Acta Crystallogr.  2008,  A64:  112 

8

Crystal Structure Study of 4b
Single-crystal X-ray diffraction studies were carried out on a Nonius KappaCCD diffractometer at 123(2) K using MoKa radiation (l = 0.71073 Å). The structures were solved by Direct Methods (SHELXS-9713) and refinement were carried out using SHELXL-9713 (full-matrix least-squares refinement on F2). The hydrogen atoms were localized by difference electron density determination and refined using a ‘riding’ model (H(O)) free).
4b: Colorless crystals, C14H18O4, M = 250.28, crystal size 0.50 x 0.45 x 0.40 mm, triclinic, space group P-1 (No.2): a = 5.9907(2) Å, b = 8.5207(3) Å, c = 12.4965(5) Å, α = 97.603(2)º, b = 95.458(2)º, g = 97.465(2)º, V = 622.81(4) Å3, Z = 2, r(calcd) = 1.335 Mg m-3, F(000) = 268, m = 0.097
mm-1, 5344 reflections (2qmax = 55˚), 2715 unique (Rint = 0.025), 168 parameters, 1 restraint, R1 (I > 2s(I)) = 0.036, wR2 (all data) = 0.104, GooF = 1.07, largest diff. peak and hole 0.264 and -0.228 e Å-3. Crystallographic data (excluding structure factors) for the structure reported in this work have been deposited with the Cambridge Crystallographic Data Centre as supplementary pub­lication no. CCDC 717754 (4b). These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

11

Selected NMR Data
Compound 4b: ^¹H NMR (400 MHz, CDCl₃): δ = 1.42 (s,
3 H), 1.57 (dd, J = 13.5, 9.8 Hz, 1 H), 1.67 (td, J = 13.5 Hz, 1 H), 2.06-2.14 (m, 2 H), 2.28 (s, 3 H), 3.70 (s, 3 H), 3.86-3.90 (m, 1 H), 4.89 (m_c, 1 H), 5.25 (m_c, 1 H), 6.13 (s, 1 H), 6.24 (s, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 21.9, 28.6, 34.7, 45.5, 55.4, 61.9, 73.9, 89.9, 102.9, 105.9, 108.5, 140.3, 156.2, 157.1.
Compound 9b: ^¹H NMR (400 MHz, CDCl₃): δ = 1.21-1.30 (m, 2 H), 1.28 (t, J = 7.3 Hz, 3 H), 2.04 (s, 3 H), 2.28 (s,
3 H), 2.59 (ddd, J = 14.1, 8.0, 1.3 Hz, 1 H), 2.72 (ddd, J = 14.1, 7.3, 1.3 Hz, 1 H), 3.26 (br s, 1 H), 3.86 (s, 3 H), 4.18 (q, J = 7.3 Hz, 2 H), 4.97 (dd, J = 5.8, 5.3 Hz, 1 H), 5.87 (ddd, J = 15.5, 1.3, 1.3 Hz, 1 H), 6.29 (s, 1 H), 6.35 (s, 1 H), 7.02 (ddd, J = 15.5, 7.8, 7.8 Hz, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.2, 21.7, 25.3, 38.7, 41.4, 55.4, 60.1, 60.2, 75.5, 103.3, 109.9, 111.0, 139.7, 144.4, 153.0, 158.2, 166.3.
Compound 10b: ^¹H NMR (400 MHz, CDCl₃): δ = 1.25 (t, J = 7.1 Hz, 3 H), 1.27 (s, 3 H), 1.53-1.67 (m, 2 H), 1.68-1.85 (m, 4 H), 2.27 (s, 3 H), 2.28-2.34 (m, 2 H), 2.55-2.64 (m, 2 H), 3.80 (s, 3 H), 4.12 (q, J = 7.1 Hz, 2 H), 6.22 (s, 1 H), 6.28 (s, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.2, 16.4, 19.2, 21.6, 23.8, 30.4, 34.5, 38.8, 55.3, 60.2, 75.4, 102.4, 107.0, 110.3, 136.9, 154.1, 157.6, 173.5.
Compound trans-11b: ^¹H NMR (400 MHz, CDCl₃): δ = 1.28 (t, J = 7.1 Hz, 3 H), 1.39 (s, 3 H), 2.30 (s, 3 H), 2.50-2.74 (m, 4 H), 3.88 (s, 3 H), 4.18 (q, J = 7.1 Hz, 2 H), 5.87 (d, J = 15.5 Hz, 1 H), 6.30 (s, 1 H), 6.37 (s, 1 H), 6.95 (ddd, J = 15.5, 7.6, 7.6 Hz, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.2, 22.4, 23.9, 41.9, 48.5, 56.0, 60.4, 79.5, 104.7, 108.4, 110.8, 125.4, 142.1, 147.7, 160.2, 160.8, 165.9, 190.0.
Compound cis-11b: ^¹H NMR (400 MHz, CDCl₃): δ = 1.27 (t, J = 7.2 Hz, 3 H), 1.39 (s, 3 H), 2.30 (s, 3 H), 2.59 (d, J = 16.0 Hz, 1 H), 2.77 (d, J = 16.0 Hz, 1 H), 3.13 (m_c, 2 H), 3.88 (s, 3 H), 4.15 (q, J = 7.2 Hz, 2 H), 5.94 (d, J = 11.7 Hz, 1 H), 6.29 (s, 1 H), 6.32-6.40 (m, 2 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.2, 22.4, 23.7, 38.3, 48.5, 56.0, 60.0, 79.9, 104.6, 108.5, 110.7, 122.7, 143.0, 147.6, 160.2, 161.0, 166.1, 190.4.
Compound 12b: ^¹H NMR (400 MHz, CDCl₃): δ = 1.22 (t, J = 7.1 Hz, 3 H), 1.36 (s, 3 H), 1.60-1.80 (m, 4 H), 2.25-2.30 (m, 2 H), 2.28 (s, 3 H), 2.56 (d, J = 15.8 Hz, 1 H), 2.70 (d, J = 15.8 Hz, 1 H), 3.86 (s, 3 H), 4.09 (q, J = 7.1 Hz, 2 H), 6.26 (s, 1 H), 6.33 (s, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 19.0, 22.3, 23.5, 34.1, 38.5, 48.6, 56.0, 60.3, 80.0, 104.3, 108.4, 110.7, 147.4, 160.1, 161.2, 173.1, 190.7.
Compound 13b: ^¹H NMR (500 MHz, CDCl₃): δ = 1.44 (s,
3 H), 1.70-1.82 (m, 1 H), 1.91-2.00 (m, 1 H), 2.00-2.08 (m, 2 H), 2.31 (s, 3 H), 2.37 (dd, J = 18.7, 5.9 Hz, 1 H), 2.48 (ddd, J = 18.7, 11.6, 6.8 Hz, 1 H), 3.92 (s, 3 H), 6.34 (s, 1 H), 6.35 (s, 1 H), 15.98 (s, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 18.3, 22.4, 25.5, 30.2, 35.9, 56.1, 78.2, 105.4, 108.2, 108.7, 111.2, 147.1, 160.2, 160.6, 180.3, 182.0.