Further Enolate Alkylation Studies of 2,5-Dimethyl-3(2H)-furanone

Drury S. Caine; Mark E. Arant

doi:10.1055/s-2004-831300

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Synlett 2004(12): 2081-2086
DOI: 10.1055/s-2004-831300

LETTER

Further Enolate Alkylation Studies of 2,5-Dimethyl-3(2H)-furanone

Drury S. Caine^a, Mark E. Arant*^b
^a Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487, USA
^b Department of Chemistry, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA
Fax: +1(318)3423334; e-Mail: arant@ulm.edu;

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Publication History

Received 17 June 2004
Publication Date:
24 August 2004 (online)

Abstract
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Abstract

Heterocyclic ketones, such as 2,5-dimethyl-3(2H)-furanone, provide multifunctional intermediates to various compounds. One property of these that has proven useful is the ability to alkylate the γ′-position of the dienolate. This report demonstrates the versatility of γ′-dienolate substitutions as employed toward syntheses of certain natural products and highly reactive electrophiles provide the best substrates for efficient substitution.

Key words

alkylations - natural products - heterocycles - protecting Groups - ketones

References

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6

SEM-Cl is available from Aldrich and BOM-Cl from Sigma-Aldrich.

8

Composition determined from ¹H NMR.

9

Trace amounts of 3b (2.5%) and 5c (2.5%) were noted in the ¹H NMR spectrum of the reaction mixture.

10

Analytical data of compound 6: 84.3% yield; bp 100 °C at 0.025 mm. IR (neat): 3100, 3080, 3040, 2980, 2920, 1695, 1600, 1490, 1450, 1430, 1385, 1350, 1150, 1110, 1060, 965, 940, 790, 730, 695 cm^-1. ¹H NMR (CDCl₃): δ = 7.20 (m, 5 H, ArH), 5.18 (s, 1 H), 3.00 (ABq, J = 13.9 Hz, 2 H), 2.06 (s, 3 H), 1.38 (s, 3 H). HRMS: m/e calcd for C₁₃H₁₄O₂: 202.0994; observed: 202.1001.

15

2-Benzyloxymethyl-2-methyl-5-phenylsulfinylmethyl-3 (2H)-furanone (10, 25% yield 1:1 mixture of diastereomers): IR (neat): 3120, 3060, 3005, 2090, 2930, 2860, 1695, 1595, 1440, 1400, 1360, 1100, 1085, 1045, 965, 905, 870, 800, 745, 690, 650 cm^-1. ¹H NMR (CDCl₃): δ = 7.62-7.25 (m, 10 H, ArH), 5.55 (s, 0.5 H), 5.35 (s, 0.5 H), 4.48 (m, 2 H), 3.95 (m, 2 H), 3.51 (m, 2 H), 1.30 (s, 1.5 H) 1.13 (s, 1.5 H). HRMS: m/e calcd for C₂₀H₂₀SO₄: 356.1082; observed: 356.1070. 2-Benzyloxymethyl-2-methyl-5-phenylsulfonyl-methyl-3 (2H)-furanone (11, 19% yield): IR (neat): 3110, 3060, 3010, 2090, 2930, 2860, 1700, 1600, 1440, 1400, 1365, 1330, 1150, 1120, 1095, 1070, 965, 900, 840, 810, 740, 690 cm^-1. ¹H NMR (CDCl₃): δ = 7.62-7.25 (m, 10 H, ArH), 5.58 (s, 1 H), 4.46 (ABq, J = 12.1 Hz, 2 H), 4.30 (ABq, J = 14.1 Hz, 2 H), 3.51 (ABq, J = 10.8 Hz, 2 H), 1.20 (s, 3 H). HRMS: m/e calcd for C₁₄H₁₅O₃ [M⁺ - C₆H₅SO₂]: 231.1021; observed: 231.1019.

18

Furanone 12 (85% yield after column chromatography, 3:1 Et₂O-hexanes): IR (neat): 3110, 3020, 2980, 2930, 2860, 1700, 1595, 1510, 1460, 1380, 1360, 1300, 1250, 1170, 1100, 1030, 920, 815, 750, 730 cm^-1. ¹H NMR (CDCl₃): δ = 7.21 (d, J = 8.5 Hz, 2 H, ArH), 6.86 (d, J = 8.5 Hz, 2 H, ArH), 5.42 (s, 1 H), 4.47 (ABq, J = 11.9 Hz, 2 H), 3.80 (s, 3 H), 3.56 (s, 2 H), 2.53 (q, J = 7.5 Hz, 2 H), 1.35 (s, 3 H), 1.24 (t, J = 7.5 Hz, 3 H). HRMS: m/e calcd for C₁₆H₂₀O₄: 276.1362; observed: 276.1352.

20

Furanone 13 (50% after column chromatography, 3:1 Et₂O-hexanes). IR (neat): 3110, 3040, 2940, 2850, 1690, 1595, 1510, 1450, 1380, 1360, 1290, 1250, 1160, 1100, 1080, 1020, 970, 810, 750, 730 cm^-1. ¹H NMR (CDCl₃): δ = 7.20 (d, J = 8.4 Hz, 2 H, ArH), 6.85 (d, J = 8.4 Hz, 2 H, ArH), 5.41 (s, 1 H), 4.47 (ABq, J = 11.9 Hz, 2 H), 3.80 (s, 3 H), 3.56 (s, 2 H), 2.51 (q, J = 7.5 Hz, 2 H), 1.65 (m, 2 H), 1.38-1.24 (m, 6 H), 1.34 (s, 3 H), 0.88 (t, J = 6.6 Hz, 3 H). HRMS: m/e calcd for C₁₂H₁₉O₂ [M⁺ - CH₃OC₆H₄CH₂O): 195.1385; observed: 195.1387.

24

Carbinol 14: IR (neat): 3400, 3100, 2920, 2860, 1660, 1530, 1510, 1445, 1395, 1345, 1335, 1170, 1120, 1060, 960 cm^-1. ¹H NMR (CDCl₃): δ = 5.44 (s, 1 H), 3.74 (ABq, J = 11.7 Hz, 2 H), 2.28 (s, 3 H), 1.38 (s, 3 H). HRMS: m/e calcd for C₇H₁₀O₃: 142.0630; observed: 142.0625.

25

The resulting oil contained greater than 95% of the tetrahydrofuranone 15 in a yield of 93%. The major isomers existed as the (2R,5S)/(2S,5R) racemate in a 2:1 ratio. Dihydrofuranone 15a was presumably favored by steric repulsion between the catalyst and the BOM group. The compound possessed these spectral properties: IR (neat): 3400, 3060, 3040, 2980, 2920, 2860, 1720, 1630, 1490, 1450, 1400, 1380, 1365, 1320, 1230, 1200, 1170, 1100, 1035, 970, 930, 920, 870, 820, 730, 695 cm^-1. ¹H NMR (CDCl₃) major diastereomer 15a: δ = 7.30 (m, 5 H), 4.65 (m, 1 H), 4.48 (ABq, J = 12.2 Hz, 2 H), 3.58 (ABq, J = 9.7 Hz, 2 H), 2.63 (dd, J _ab = 18.0 Hz, J _bc = 6.1 Hz, 1 H), 2.16 (dd, J _ab = 17.5 Hz, J _bc = 10.6 Hz, 1 H), 1.39 (d, J = 6.1 Hz, 3 H), 1.18 (s, 3 H); minor diastereomer 15b: δ = 7.30 (m, 5 H), 4.54 (ABq, J = 12.0 Hz, 2 H), 4.33 (m, 1 H), 3.52 (ABq, J = 10.1 Hz, 2 H), 2.55 (dd, J _ab = 17.6 Hz, J _bc = 5.6 Hz, 1 H), 2.25 (dd, J _ab = 18.2 Hz, J _bc = 9.5 Hz, 1 H), 1.45 (d, J = 6.0 Hz, 3 H), 1.14 (s, 3 H). HRMS: m/e calcd for C₁₄H₁₈O₃: 234.1256; observed: 234.1234.