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.

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 

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.

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 

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.

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