Polymer-Supported Synthesis of α- and β-Hydroxyketones through the Formation of 1,3-Dithiane Intermediates

Abstract

The synthesis of polymer-supported 2-monosubstituted 1,3-dithianes from soluble copolymers bearing 1,3-propanedithiol groups, their lithiation, reactions with electrophiles such as aldehydes, ketones, α,β-unsaturated ketones and oxiranes, and cleavage of the produced dithioketal-protected α- or β-hydroxyketones with various reagents have been studied.

Key words

solid-phase synthesis - polymeric dithiols - polymeric dithianes - lithiation - umpolung

References and Notes

• 1 Bertini V. Lucchesini F. Pocci M. De Munno A. Tetrahedron Lett.  1998,  39:  9263 
• 2 Bertini V. Lucchesini F. Pocci M. De Munno A. J. Org. Chem.  2000,  65:  4839 
• 3 Bertini V. Pocci M. Lucchesini F. Alfei S. De Munno A. Synlett  2003,  1201 
• 4 Eliel EL. Hartmann AA. Abatjoglou AG. J. Am. Chem. Soc.  1974,  96:  1807 
• 5 Lucchesini F. Bertini V. Pocci M. Micali E. De Munno A. Eur. J. Org. Chem.  2002,  1546 
• 6 Bulman Page PC. Van Niel MB. Prodger JC. Tetrahedron  1989,  45:  7643 
• 7 Corey EJ. Erickson BW. J. Org. Chem.  1971,  36:  3553 
• 8 Bulman Page PC. Graham AE. Park KB. Tetrahedron  1992,  48:  7265 
• 9 Stork G. Zhao K. Tetrahedron Lett.  1989,  30:  287 
• 11 Ostrowski PC. Kane VV. Tetrahedron Lett.  1977,  3549 
• 12 Sikorski WH. Reich HJ. J. Am. Chem. Soc.  2001,  123:  6527 
• 14 Tenza K. Northen JS. O’Hagan D. Slawin AMZ. J. Fluorine Chem.  2004,  125:  1779 
• 15 Reeve W. Christoffel I. J. Am. Chem. Soc.  1950,  72:  1480 
• 16 Fukuzawa S. Sakai S. Bull. Chem. Soc. Jpn.  1992,  65:  3308 
• 17 De Dobbeleer C. Ates A. Vanherk J.-C. Markò IE. Tetrahedron Lett.  2005,  46:  3889 
• 18 Barluenga J. Álvarez-Pérez M. Wuerth K. Rodriguez F. Fañanás F. Org. Lett.  2003,  5:  905 

10

Acetylation of Copolymer P3ad A mixture of P3ad (0.483 g), anhyd pyridine (7.5 mL), and Ac₂O (0.7 mL) was left 3 d at r.t., precipitated in H₂O (80 mL), washed with H₂O, then with MeOH, and pump-dried up to constant weight to afford P6ad (0.495 g). IR (KBr): 1747, 1226 (ester) cm^-1.

13

3-Benzoyl-2-cyclohexen-1-ol (8ah)
Oil. IR (film, KBr): 3437 (OH), 1678 (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.55-1.76 (m, 2 H, 5-H and 6-H), 1.81-1.95 (m, 1 H, 5-H), 1.95-2.06 (m, 1 H, 6-H), 2.13 (br, 1 H, OH), 2.40 (m, 2 H, 4-H), 4.43 (br m, 1 H, 1-H), 6.43 (m, 1 H, 2-H), 7.37-7.55 (m, 3 H, arom. H), 7.65-7.70 (m, 2 H, arom. H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 19.1 (5-C), 24.2 (4-C), 31.4 (6-C), 66.3 (1-C), 128.2 (3′-C), 129.3 (2′-C), 131.9 (4′-C), 137.7 (3-C or 1′-C), 139.9 (1′-C or 3-C), 142.6 (2-C), 198.2 (C=O, ketone). MS (EI): m/z (%) = 202 (41) [M⁺]. Anal. Calcd for C₁₃H₁₄O₂: C, 77.20; H, 6.98. Found: C, 77.01; H, 7.02.