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

Drury S. Caine; Mark E. Arant

doi:10.1055/s-2004-831300

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook Linkedin Weibo

Download PDF

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;

Further Information

Publication History

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

Abstract
Full Text
References

Permissions and Reprints 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

References

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

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

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

Thieme Connect Search in Google Scholar
2b Caine DS. Paige MA. Synlett 1999, 1391

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

Search in Google Scholar
4a Caine D. Arant ME. Tetrahedron Lett. 1994, 35: 6795

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

Crossref Search in Google Scholar
4c Boeckman RK. Yoon SK. Heckendorn DK. J. Am. Chem. Soc. 1991, 113: 9682

Crossref Search in Google Scholar
5a Stork G. Isobe M. J. Am. Chem. Soc. 1975, 97: 6260

Search in Google Scholar
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

Search in Google Scholar
7a Kozikowski AP. Wu JP. Tetrahedron Lett. 1987, 28: 5125

Crossref Search in Google Scholar
7b Corey EJ. Bock MG. Tetrahedron Lett. 1975, 16: 3269

Crossref Search in Google Scholar
11 Mortia Y. Suzuki M. Noyori R. J. Org. Chem. 1989, 54: 1785

Search in Google Scholar
12 Trost B. Acc. Chem. Res. 1978, 11: 453

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

Search in Google Scholar
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.
16 Tsuge O. Kanemasa S. Suga H. Chem. Lett. 1987, 323
17 Bates RB. Taylor SR. J. Org. Chem. 1993, 58: 4469

Crossref Search in Google Scholar
19 Beard CD. Baum K. Grakauskas V. J. Org. Chem. 1973, 38: 3673

Search in Google Scholar
21a Lipshutz BH. Miller TA. Tetrahedron Lett. 1989, 30: 7149

Search in Google Scholar
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

Crossref Search in Google Scholar
23a Pearlman WM. Tetrahedron Lett. 1967, 23: 1663

Thieme Connect Search in Google Scholar
23b Hanessian S. Liak TJ. Vanasse B. Synthesis 1981, 396

Thieme Connect
23c
The catalyst showed reduced activity as it was exposed to the atmosphere. Its activity returned upon drying under mild heat and vacuum.

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

Crossref Search in Google Scholar
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

Crossref Search in Google Scholar

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.