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

Drury S. Caine; Mark E. Arant

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;

Abstract

All articles of this category

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

Full Text

References

1a Venturello C. D’Aloisio R. Synthesis 1977, 754

1b Chimichi S. Boccalini M. Cosimelli B. Acqua FD. Viola G. Tetrahedron 2003, 59: 5215

2a Smith AB. Levenberg PA. Jerris PJ. Scarborough RM. Wovkulich PM. J. Am. Chem. Soc. 1981, 103: 1501

2b Caine DS. Paige MA. Synlett 1999, 1391

3 Smith AB. Levenberg PA. Jerris PJ. Scarborough RM. Wovkulich PM. J. Am. Chem. Soc. 1981, 103: 219

4a Caine D. Arant ME. Tetrahedron Lett. 1994, 35: 6795

4b Takao K. Ochiai H. Yoshida K. Hashizuka T. Koshimura H. Tadano K. Ogawa S. J. Org. Chem. 1995, 60: 8179

4c Boeckman RK. Yoon SK. Heckendorn DK. J. Am. Chem. Soc. 1991, 113: 9682

5a Stork G. Isobe M. J. Am. Chem. Soc. 1975, 97: 6260

5b Masaki Y. Iwata I. Mukai I. Oda H. Nagashima H. Chem. Lett. 1989, 659

5c Lipshutz BH. Moretti R. Crow R. Tetrahadron Lett. 1989, 30: 15

6

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

7a Kozikowski AP. Wu JP. Tetrahedron Lett. 1987, 28: 5125

7b Corey EJ. Bock MG. Tetrahedron Lett. 1975, 16: 3269

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.

11 Mortia Y. Suzuki M. Noyori R. J. Org. Chem. 1989, 54: 1785

12 Trost B. Acc. Chem. Res. 1978, 11: 453

13 Fieser LF. Fieser M. Reagents for Organic Synthesis Vol. 5: John Wiley and Sons; New York: 1975. p.523

14 Analytical data of compound 8: 65% yield. IR (neat): 3100, 3050, 3020, 2920, 2860, 1695, 1580, 1470, 1445, 1430, 1360, 1180, 1100, 1060, 800, 735, 695 cm^-1. ¹H NMR (CDCl₃): δ = 7.39-7.22 (m, 10 H, ArH), 5.46 (s, 1 H), 4.51 (ABq, J = 12.3 Hz, 2 H), 3.82 (s, 2 H), 3.59 (ABq, J = 8.8 Hz, 2 H), 1.31 (s, 3 H). HRMS: m/e calcd for C₂₀H₂₀SO₃: 340.1133; observed: 340.1145.

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.

16 Tsuge O. Kanemasa S. Suga H. Chem. Lett. 1987, 323

17 Bates RB. Taylor SR. J. Org. Chem. 1993, 58: 4469

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.

19 Beard CD. Baum K. Grakauskas V. J. Org. Chem. 1973, 38: 3673

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.

21a Lipshutz BH. Miller TA. Tetrahedron Lett. 1989, 30: 7149

21b Suzuki K. Matusumoto T. Tomooka K. Matsumoto K. Tsuchihashi GI. Chem. Lett. 1987, 113

22 Heathcock CH. Ratcliff JR. J. Am. Chem. Soc. 1971, 93: 1746

23a Pearlman WM. Tetrahedron Lett. 1967, 23: 1663

23b Hanessian S. Liak TJ. Vanasse B. Synthesis 1981, 396

23c

The catalyst showed reduced activity as it was exposed to the atmosphere. Its activity returned upon drying under mild heat and vacuum.

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.

26 Czech BP. Bartsch RA. J. Org. Chem. 1984, 49: 4076

27 For example: Nicolau KC. Hwang CK. Marron BE. DeFrees SA. Couladouros EA. Abe Y. Carroll PJ. Snyder JP. J. Am. Chem. Soc. 1990, 112: 3040