Manganese(III) Acetate-mediated Alkylation of 1,3-Dicarbonyls to Form Tricarbonyl Compounds Bearing a Quaternary Carbon Centre

Abstract

1,3-Dicarbonyl compounds including ethyl 2-methylacetoacetate can be efficiently alkylated with enol ethers or enol esters in the presence of manganese(III) acetate. These intermolecular radical addition reactions can be used to form sterically congested quaternary carbon centres in excellent yield (81-97%).

aldehydes - alkylations - ketones - manganese - radical reactions

References

1 Snider BB. Chem. Rev.  1996,  96:  339 

2 Linker T. J. Prakt. Chem.  1997,  339:  488 

3 Melikyan GG. Aldrichimica Acta  1998,  31:  50 

4 Parsons AF. An Introduction to Free Radical Chemistry   Blackwell Science; Oxford: 2000. 

5 For a recent example see: Snider BB. Smith RB. Tetrahedron  2002,  58:  25 

6 Nédélec JY. Nohair K. Synlett  1991,  659 

7 Nishino H. Tategami S.-i. Yamada T. Korp JD. Kurosawa K. Bull. Chem. Soc. Jpn.  1991,  64:  1800 

8 Heiba EI. Dessau RM. J. Org. Chem.  1974,  39:  3456 

9 Lavilla R. Spada A. Carranco I. Bosch J. J. Org. Chem.  2001,  66:  1487 

10 Kumabe R. Nishino H. Yasutake M. Nguyen V.-H. Kurosawa K. Tetrahedron Lett.  2001,  42:  69 

11 Allegretti M. D’Annibale A. Trogolo C. Tetrahedron  1993,  49:  10705 

12 Midgley G. Thomas CB. J. Chem. Soc., Perkin Trans. 2  1987,  1103 

13 Bar G. Parsons AF. Thomas CB. Tetrahedron  2001,  57:  4719 

14 Montevecchi PC. Navacchia ML. Tetrahedron  2000,  56:  9339 

15 Corey EJ. Ghosh AK. Chem. Lett.  1987,  223 

16 Mellor JM. Mohammed S. Tetrahedron  1993,  49:  7547 

17 Mellor JM. Mohammed S. Tetrahedron  1993,  49:  7557 

18 Corey EJ. Ghosh AK. Tetrahedron Lett.  1987,  28:  175 

19

Copper(II) acetate is often added as a co-oxidant in manganese(III) acetate-mediated radical reactions (see ref. [1] ).

20

All new compounds exhibited satisfactory spectral and analytical (high-resolution mass) data. Some of the 1,4-dicarbonyl products underwent slow decomposition (e.g. aerial oxidation) and so these types of compounds should be stored appropriately or used immediately.

21

Typical Experimental Procedure: To ethyl 2-methyl-acetoacetate 11 (0.2 g, 1.38 mmol) in degassed dichloro-methane (10 cm³) was added butyl vinyl ether (0.77 g, 6 equiv, 8.32 mmol) followed by manganese(III) acetate dihydrate (0.86 g, 2.3 equiv, 3.19 mmol) and copper(II) acetate monohydrate (0.09 g, 0.3 equiv, 0.41 mmol). The solution was heated to reflux overnight (typically 18 h). Dichloromethane (40 cm³) was then added and the resulting suspension removed by filtration. The solution was washed with water (10 cm³), dried (MgSO₄) and following evaporation in vacuo the crude product was purified using column chromatography(silica) to give ethyl 2-methyl-2-(oxoethyl)acetoacetate 12 (0.24 g, 92%) as a colourless oil; R_f = 0.45 (7:3 dichloromethane:ethyl acetate); IR (CHCl₃): ν_max = 3060 (w, br), 2985 (w, br), 1716 (s, br), 1723 (s, sh), 1461 (m, sh), 1277 (s, br) cm^-1; ¹H NMR (300 MHz, CDCl₃): δ = 9.63 (1 H, s, HC=O), 4.14 (2 H, q, J = 7 Hz, O-CH ₂-CH₃), 2.93 and 2.83 (2 H, 2 × d, J = 19 Hz, O=CH-CH ₂-C), 2.18 (3 H, s, CH₃-C=O), 1.44 (3 H, s, CH₃-C-C=O), 1.19 (3 H, t, J = 7.0 Hz, O-CH₂-CH ₃); ¹³C NMR (75 MHz, CDCl₃): δ = 203.7 (CH₃-C=O), 198.2 (H-C=O), 170.6 (O=C-O), 60.9 (O-CH₂-CH₃), 56.0 (O=C-C-CH₃), 47.6 (O=CH-CH₂-C), 25.0 (CH₃-C=O), 19.4 (CH₃-C-C=O), 12.9 (O-CH₂-CH₃); MS: m/z (%)= (CI, NH₃) 203(100) [M⁺ - 1 + NH₄ ⁺], 187(82) [M + H⁺], 185(62), 169(43) (Found: [M + H⁺] 187.0967. C₉H₁₅O₄ requires for [M + H⁺] 187.0970).

22 The formation of radical 13 from acetoacetate 11 is supported by the fact that, in the absence of double bond acceptors, reaction of 11 with manganese(III) acetate produces dimeric and polymeric products: Snider BB. Patricia JJ. Kates SA. J. Org. Chem.  1988,  53:  2137 

23 For reaction of acetoacetate 11 with manganese(III) acetate in the presence of alkenes see: Snider BB. Zhang Q. Dombroski MA. J. Org. Chem.  1992,  57:  4195 

24 Iqbal J. Srivastava RR. Khan MA. Tetrahedron Lett.  1990,  31:  1485 

25 Nair V. Mathew J. Prabhakaran J. Chem. Soc. Rev.  1997,  127 

26a Gu X.-P. Nishida N. Ikeda I. Okahara M. J. Org. Chem.  1987,  52:  3192 

26b Gu X.-P. Okuhara T. Ikeda I. Okahara M. Synthesis  1988,  535 

26c Ikeda I. Gu X.-P. Okuhara T. Okahara M. Synthesis  1990,  32 

26d Hori Y. Mitsudo T.-a. Watanabe Y. Tetrahedron Lett.  1986,  27:  5389 

27 Chiu P.-K. Sammes MP. Tetrahedron  1990,  46:  3439 

28 For an alternative approach to 1,4-dicarbonyl compounds from β-keto esters see: Brogan JB. Zercher CK. J. Org. Chem.  1997,  62:  6444 

29 For related γ-lactols see for example: Manny AJ. Kjelleberg S. Kumar N. de Nys R. Read RW. Steinberg P. Tetrahedron  1997,  53:  15813 

30 For a similar benzyl ester deprotection followed by decarboxylation reaction see: Gribble GW. Switzer FL. Soll RM. J. Org. Chem.  1988,  53:  3164 

31 Christoffers J. Mann A. Angew. Chem. Int. Ed.  2001,  40:  4591 

32a Sibi MP. Porter NA. Acc. Chem. Res.  1999,  32:  163 

32b Yang D. Gu S. Yan Y.-L. Zhu N.-Y. Cheung K.-K. J. Am. Chem. Soc.  2001,  123:  8612 

32c Renaud P. Gerster M. Angew. Chem. Int. Ed.  1998,  37:  2562