RSS-Feed abonnieren
DOI: 10.1055/s-2008-1077878
Synthesis and Evaluation of Enantiopure 6-Thiabicyclo[3.2.1]octanes for Asymmetric Epoxidation of Benzaldehyde
Publikationsverlauf
Publikationsdatum:
11. Juni 2008 (online)
Abstract
A one-step synthesis of 6-thiabicyclo[3.2.1]octan-3-one from carvone is reported. Chiral sulfides were subsequently elaborated in a few steps and used as competent sulfonium ylide promoters for the asymmetric epoxidation of aldehydes. Their odourant characteristics are also described.
Key words
sulfur - ylides - epoxidations - catalysis - asymmetric
- For recent reviews on sulfide in enantioselective catalysis, see:
-
1a
Pellissier H. Tetrahedron 2007, 63: 1297 -
1b
Mellah M.Voituriez A.Schulz E. Chem. Rev. 2007, 107: 5133 -
1c
McGarrigle EM.Myers EL.Illa O.Shaw MA.Riches SL.Aggarwal VK. Chem. Rev. 2007, 107: 5841 -
1d
McGarrigle EM.Aggarwal VK. Enantioselective Organocatalysis: Reactions and Experimental ProceduresDalko PI. Wiley-VCH; Weinheim: 2007. Chap. 10. -
1e
Seayad J.List B. Org. Biomol. Chem. 2005, 3: 719 - For recent reviews on chiral odorants, see:
-
2a
Goeke A. Sulfur Rep. 2002, 23: 243 -
2b
Brenna E.Fuganti C.Serra S. Tetrahedron: Asymmetry 2003, 14: 1 -
2c
Bentley R. Chem. Rev. 2006, 106: 4099 -
3a
Demole E.Enggist P.Ohloff G. Helv. Chim. Acta 1982, 65: 1785 -
3b
Lehmann D.Dietrich A.Hener U.Mosandl A. Phytochem. Anal. 1995, 6: 255 ; and references cited therein -
4a
Weitkamp AW. J. Am. Chem. Soc. 1959, 81: 3437 -
4b
Moore CG.Porter M. Tetrahedron 1959, 6: 10 -
4c
Bertaina C.Cozzolino F.Fellous R.George G.Rouvier E. Parfums Cosmét. Arômes 1986, 71: 69 -
4d
Janes JF.Marr IM.Unwin N.Banthorpe DV.Yusuf A. Flavour Frag. J. 1993, 8: 289 -
5a
Hargreaves M.McDougall R.Rabari L. Z. Naturforsch., B: Anorg. Chem. Org. Chem. 1978, 33: 1535 -
5b
Krein EB.Aizenshtat Z. J. Org. Chem. 1993, 58: 6103 -
5c
Sirazieva EV.Startseva VA.Nikitina LE.Sofronov AV.Artemova NP.Fedyunina IV. Chem. Nat. Compd. 2007, 43: 52 -
6a Review on polysulfane:
Steudel R. Chem. Rev. 2007, 102: 3905 -
6b Recent paper:
Aebisher D.Brzostowska EM.Mahendran A.Greer A. J. Org. Chem. 2007, 72: 2951 ; and references cited therein - For recent reviews, see:
-
7a
Aggarwal VK.Richardson J. Chem. Commun. 2003, 2644 -
7b
Aggarwal VK.Winn CL. Acc. Chem. Res. 2004, 37: 611 ; see also ref. 1c -
10a
Ranu BC.Mandal T. Synlett 2007, 925 -
10b
Lou F.-W.Xu J.-M.Liu B.-K.Wu Q.Pan Q.Lin X.-F. Tetrahedron Lett. 2007, 48: 2815 -
10c
Weïwer M.Coulombel L.Duñach E. Chem. Commun. 2006, 332 ; and references cited therein - 11
Yan T.-H.Tsai C.-C.Chien C.-T.Cho C.-C.Huang P.-C. Org. Lett. 2004, 6: 4961 - For selected recent examples, see:
-
16a
Winn CL.Bellenie BR.Goodman JM. Tetrahedron Lett. 2002, 43: 5427 -
16b
Aggarwal VK.Alonso E.Bae I.Hynd G.Lydon KM.Palmer MJ.Patel M.Porcelloni M.Richardson J.Stenson RA.Studley JR.Vasse J.-L.Winn CL. J. Am. Chem. Soc. 2003, 125: 10926 -
16c
Deng X.-M.Cai J.Ye S.Sun X.-L.Liao W.-W.Li K.Tang Y.Wu Y.-D.Dai LX. J. Am. Chem. Soc. 2006, 128: 9730 -
16d
Davoust M.Brière J.-F.Jaffrès P.-A.Metzner P. J. Org. Chem. 2005, 70: 4166 ; and references cited therein -
17a
Silva MA.Bellenie BR.Goodman JM. Org. Lett. 2004, 61: 2559 -
17b
Edwards DR.Montoya-Peleaz P.Crudden CM. Org. Lett. 2007, 9: 5481 -
17c
For exhaustive studies on sulfonium ylide mechanism, see also ref. 1c, 7a.
- 20
Jaubert J.-N.Tapiero C.Dore J.-C. Perfum. Flav. 1995, 20: 1
References and Notes
The aqueous solutions of (NH4)2S (20% or 50%) are commercially available from Aldrich.
9
Synthesis of 4,7,7-Trimethyl-6-thia-1,5-bicyclo[3.2.1]octan-3-one
(5)
A 50% aq solution of diammonium sulfide (20 mL, 146.8 mmol) was added dropwise to a mixture of TBAB (1.544 g, 4.8 mmol) and elemental sulfur (4.689 g, 146.2 mmol). The solution was stirred for 5 min. Then, THF (9 mL) was added and carvone (15 mL, 93.8 mmol) was slowly introduced. The obtained red solution was vigorously stirred at r.t. for 3-4 d (until carvone disappeared on TLC). The solution was diluted in H2O (100 mL), and the product was extracted with Et2O (3 × 50 mL). The combined organic layers were washed with a sat. aq solution of NH4Cl (15 mL), a sat. aq solution of K2CO3 (15 mL) and brine (15 mL). The organic layer was dried over MgSO4, filtrated, and concentrated in vacuo. The obtained oil was purified by flash column chromatography (heptane-EtOAc, 5:1) to afford an inseparable mixture of diastereomers as an oil which crystallised as a yellow powder (59%, 86:14 eq/ax). Trituration in i-PrOH facilitated the crystallisation without changing the diastereomeric ratio. This is a stable compound, which could be stored for at least a year in the fridge. Melting point and optical rotation of the 86:14 mixture of diastereomers are given for indication: mp 65-67 °C (lit5b 67-68 °C for the pure equatorial compound 5), [α]D
20 +116 (c 1.0, CHCl3). 1H NMR (250 MHz, CDCl3):
δ = 1.08 (d, J = 6.5 Hz, 3 H, eq), 1.19 (d, J = 7.5 Hz, 3 H, ax), 1.38 (s, 3 H, eq), 1.43 (s, 3 H, ax), 1.44 (s, 3 H, eq + ax), 2.27-2.43 (m, 3 H, eq + ax), 2.62-2.71 (m, 3 H, eq + ax), 3.47 (br s, 1 H, eq + ax). 13C NMR (63 MHz, CDCl3):
δ (eq) = 209.1, 54.8, 52.5, 52.1, 49.6, 44.9, 41.1, 34.0, 27.1, 13.7; δ (ax) = 212.6, 54.3, 49.9, 48.9, 42.1, 33.9, 33.8, 24.5, 17.4. IR (neat): 2951, 1698. HRMS: m/z calcd for C10H17OS [M + H]+: 185.1000; found: 185.1007. GC-MS: 2 peaks with the same mass(184). Enantioselective GC was performed on a CYDEX-B chiral capillary column (25 m × 0.22 mm), 10 psi at 130 °C; t
R (enantiomers of the major epimer 5) = 47.7 and 49.5.
4,7,7-Trimethyl-3-methylene-6-thiabi-cyclo[3.2.1]octane
(7)
Obtained as a mixture of epimers (58 mg, 95:5 eq/ax) after column-chromatography purification (pentane-Et2O, 30:1); colourless liquid. 1H NMR (250 MHz, CDCl3): δ = 1.02 (d, J = 6.5 Hz, 3 H, eq), 1.15 (d, J = 7.3 Hz, 3 H, ax), 1.39 (s, 3 H, eq + ax), 1.43 (s, 3 H, eq), 1.50 (s, 3 H, ax), 1.98-2.22 (m, 3 H, eq + ax), 2.44-2.54 (m, 3 H, eq + ax), 3.47 (br s, 1 H, eq + ax), 4.80-4.90 (m, 2 H, eq + ax). 13C NMR (63 MHz, CDCl3): δ (main equatorial isomer) = 148.3, 112.8, 54.9, 53.8, 48.2, 42.6, 42.4, 38.5, 34.4, 25.5, 17.3. IR (neat): 1641, 1455, 886. HRMS: m/z calcd for C11H18S [M]+: 182.1129; found: 182.1126.
4,7,7-Trimethyl-3-phenyl-6-thiabicyclo[3.2.1]octan-3-ol
(8)
A small sample was purified on column chromatography (heptane-Et2O, 30:1) for analytical purposes. Only one diastereomer is seen by NMR. White solid; mp 116-118 °C. 1H NMR (250 MHz, CDCl3): δ = 0.77 (d, J = 6.9 Hz, 3 H), 1.51 (s, 3 H), 1.72 (s, 3 H) 2.05 (dd, J = 4.5, 15.2 Hz, 1 H), 2.15 (d, J = 12.0 Hz, 1 H), 2.19-2.26 (m, 1 H), 2.27-2.38 (m, 2 H), 2.58-2.67 (m, 1 H), 3.46 (br d, J = 7.1 Hz, 1 H), 5.20 (s, 1 H, OH), 7.16-7.35 (m, 3 H), 7.46-7.50 (m, 2 H).
13C NMR (63 MHz, CDCl3): δ = 148.2, 127.9, 126.3, 125.4, 75.9, 55.2, 53.4, 49.5, 46.1, 44.4, 41.7, 35.0, 27.3, 14.3.
IR (neat): 3369, 2929, 1492, 1448, 1382. MS (EI):
m/z (%) = 262 (46), 244 (80).
4,7,7-Trimethyl-3-phenyl-6-thiabicyclo[3.2.1]oct-2-ene
(9)
Obtained as a mixture of epimers (191 mg, 80:20 eq/ax) after column-chromatography purification (heptane-Et2O, 50:1). Yellow oil. 1H NMR (250 MHz, CDCl3): δ = 0.64 (d, J = 6.4 Hz, 3 H, ax), 0.91 (d, J = 7.2 Hz, 3 H, eq), 1.44 (s, 3 H, ax), 1.47 (s, 3 H, eq), 1.49 (s, 3 H, eq), 1.51 (s, 3 H, ax), 2.19-2.27 (m, 1 H, eq + ax), 2.31-2.44 (m, 1 H, eq + ax), 2.45-2.55 (m, 1 H, eq + ax), 3.15-3.23 (m, 1 H, eq + ax), 3.58 (t, J = 4.4 Hz, 1 H, eq + ax), 5.27-5.37 (m, 1 H, ax), 5.82 (br d, J = 6.6 Hz, 1 H, eq), 7.18-7.28 (m, 5 H, eq + ax). 13C NMR (63 MHz, CDCl3): δ (eq) = 141.9, 141.4, 128.4, 128.2, 126.8, 126.8, 60.5, 53.6, 48.4, 39.9, 38.8, 33.4, 27.6, 17.3; δ (ax) = 143.6, 128.3, 128.1, 127.1, 127.0, 54.8, 48.8, 48.1, 47.0, 35.0, 33.0, 25.9, 13.5; one sp2 signal is overlapping with one equatorial signal. IR (neat): 2927, 1777, 1599, 1453. HRMS: m/z calcd for C16H21S [M + H]+: 245.1364; found: 245.1360.
3-Methoxy-4,7,7-trimethyl-6-thiabi-cyclo[3.2.1]octane
(11)
Obtained as a mixture of epimers (379 mg, 98:2 eq/ax) after column-chromatography purification (heptane-Et2O, 20:1). Colourless oil. 1H NMR (400 MHz, CDCl3): δ (main equatorial isomer) = 0.99 (d, J = 6.9 Hz, 3 H), 1.43 (s, 3 H), 1.52 (s, 3 H), 1.54-1.59 (m, 1 H), 1.83-1.86 (m, 1 H), 1.96-1.99 (m, 1 H), 2.13-2.08 (m, 1 H), 2.25-2.30 (m, 1 H), 2.45-2.50 (m, 1 H), 3.14-3.16 (m, 1 H), 3.21 (t, J = 5.8 Hz, 1 H), 3.29 (s, 3 H). 13C NMR (63 MHz, CDCl3): δ (eq) = 78.4, 57.7, 53.5, 51.7, 47.0, 42.1, 41.8, 35.5, 30.5, 26.9, 16.3. IR (neat): 2923, 1459, 1115, 1091. HRMS: m/z calcd for C11H21OS [M + H]+: 201.1313; found: 201.1316.
The determination of odour concentration was carried out at IAP-SENTIC company (France) by dynamic olfactometry according to the European standard EN13725 with trained 4 or 6 sensory assessors. Sample preparation: 10-20 mg of compounds were solubilised in 2 g of abs. EtOH (solution 1) and diluted 100 times (solution 2). Then, 25 µL of either solution 1 or 2 were injected within 10 l of air and analysed.
19The odorant factor is defined as the maximum volume (m3) in which 1 g of compound could be detected (by the nose of assessors). The odorant factor of limonene-thiol 3 (from Sigma Aldrich - CAS 71159-90-5) was evaluated to 11·106 by the method described in ref. 18.