A Short Synthesis of Preussin: Use of Allyldimethylsilyl as Masked Hydroxyl [1]

Abstract

A short and efficient synthesis of Preussin utilizing allyldimethylsilyl group as hydroxyl equivalent via an interesting (3+2) annulation reaction involving non-classical pentavalent silicon cation transition state, has been described.

Keywords

natural product - antifungal agents - (3+2) annulation - allydimethylsilyl - pyrrolidine alkaloid

1

Communication no. 6415 from CDRI.

References

• 2a Schwartz RE. Liesch J. Hensens O. Zitano L. Honeycutt S. Garrity G. Fromtling RA. Onishi J. Monaghan R. J. Antibiot.  1988,  41:  1774 
• 2b Johnson JH. Phillipson DW. Khale AD. J. Antibiot.  1989,  42:  1185 
• 3a Pak CS. Lee GH. J. Org. Chem.  1991,  56:  1128 
• 3b McGrane PL. Livinghouse T. J. Am. Chem. Soc.  1993,  115:  11485 
• 3c Shimazaki M. Okazaki F. Nakajima F. Ishikawa T. Ohta A. Heterocycles  1993,  36:  1823 
• 3d Overhand M. Hecht SM. J. Org. Chem.  1994,  59:  4721 
• 3e Kanazawa A. Gillet S. Delair P. Greene AE. J. Org. Chem.  1998,  63:  4660 
• 3f Bach T. Brummerhop H. Angew. Chem. Int. Ed.  1998,  37:  3400 
• 3g Verma R. Ghosh SK. J. Chem. Soc., Perkin Trans. 1  1999,  265 
• 3h Lee K.-Y. Kim Y.-H. Oh C.-Y. Ham W.-H. Org. Lett.  2000,  2:  4041 
• 3i Veeresa G. Datta A. Tetrahedron  1998,  54:  15673 
• 4 Kasahara K. Yoshida M. Eishima J. Takasako K. Beppu T. Horinouchi S. J. Antibiot.  1997,  50:  267 
• 5 Achenbach TV. Slater EP. Brummerhop H. Bach T. Müller R. Antimicrob. Agents Chemother.  2000,  44:  2794 
• 6 Kinzy TG. Harger JW. Schmid AC. Kwon J. Shastry M. Justice M. Dinman D. Virology  2002,  300:  60 
• 7a Tamao K. Ishida N. Tetrahedron Lett.  1984,  25:  4249 
• 7b Tamao K. Ishida N. Tanaka T. Kumada M. Organometallics  1983,  2:  1694 
• 7c Tamao K. Ishida N. J. Organomet. Chem.  1984,  269:  C37 
• 7d Fleming I. Henning R. Plaut H. J. Chem. Soc., Chem. Commun.  1984,  29 
• 7e Fleming I. Sanderson PEJ. Tetrahedron Lett.  1987,  28:  4229 
• 7f Fleming I. Chan TH. Synthesis  1979,  762 
• 8 Fleming I. Henning R. Parker DC. Plaut HE. Sanderson PEJ. J. Chem. Soc., Perkin Trans. 1  1995,  317 
• 9 Kiyooka S.-i. Shiomi Y. Kira H. Kaneko Y. Tanimori S. J. Org. Chem.  1994,  59:  1958 
• 10a

  All the spectral data of compound 2a and 4 matched fully with that of authentic sample, kindly provided by Prof. Kiyooka.

• 10b Our attempts to cleave trimethylsilyl group on 2a to give synthetically useful intermediate met with no success. Reported TFA catalysed cleavage gave the ring open product 7: Martin D. Gamal M. Synthesis  1982,  827 
• 10c While t-BuOK catalyzed cleavage conditions gave 8 (Scheme 4): Price CC. Sowa JC. J. Org. Chem.  1967,  32:  4126 
• 11 Magar SS. Fuchs PL. Tetrahedron Lett.  1991,  32:  7513 
• 16a Beier C. Schaumann E. Synthesis  1997,  1296 
• 16b Krasinski A. Gruza H. Jurczak J. Heterocycles  2001,  54:  581 

1

Communication no. 6415 from CDRI.

12

Synthesis of Compound 2c: To a stirred soln of (S)-2-(N-benzyloxycarbonylamino)-3-phenyl-propanal (1 g, 3.5 mmol) in 20 mL of freshly dried CH₂Cl₂ at -10 °C was added BF₃·OEt₂ (0.09 mL, 0.4 mmol). After 20 min a solution of diallyldimethylsilane (0.69 mL, 3.8 mmol) in freshly dried CH₂Cl₂ (4 mL) was added to it drop wise over a period of 10 min, the resultant mixture was stirred for 2 h at -10 °C, quenched with aq NH₄Cl solution (25 mL) and extracted with CH₂Cl₂ (50 mL × 3). Combined organic layer was washed with brine, dried over anhyd Na₂SO₄ and concentrated. The crude material was flash chromatographed over silica gel using 12% EtOAc-hexane as eluent to give pure 2c. Data of 2c: Colourless oil (1.03 g, 70%); [α]_D = -61.09 (c 0.293, MeOH). IR(neat): 3432, 2956, 1680, 1502,1416 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.2 (m, 10 H), 5.7 (m, 1 H), 5.0 (d, J = 12 Hz, 2 H), 4.8 (dd, J = 15.8 and 11.0 Hz, 2 H), 4.2 (m, 2 H), 3.8 (m, 1 H), 2.9 (d, J = 5.3 Hz, 2 H), 2.2 (m, 1 H), 1.6 (m, 4 H), 0.81 (dd, J = 12.9 and 11.7 Hz, 1 H), -0.019 (s, 6 H). ¹³C NMR (200 MHz, CDCl₃): δ = 155.1, 139.3, 136.6, 134.6, 129.8, 129.5, 128.39, 128.32, 128.0, 127.9, 126.1, 113.1, 71.4, 66.7, 62.4, 53.9, 39.7, 36.0, 24.1, 23.5, -2.9, -3.2; FABMS: m/z = 424 (M + 1), 383, 292.

13

Synthesis of Compound 2d: To a solution of 2c (800 mg, 1.89 mmol) in CH₂Cl₂ (20 mL) at 0 °C were successively added Et₃N (2.6 mL, 18.9 mmol) and Ac₂O (0.9 mL, 9.4 mmol) followed by DMAP (50 mg) as catalyst. The resulting mixture was stirred at r.t. for 4 h, diluted with CH₂Cl₂ (50 mL), taken in a separating funnel and washed s uccessively with 5% HCl (25 mL), sat. NaHCO₃ (25 mL) and brine (25 mL). The organic layer was dried over anhyd Na₂SO_4, concd in vacuo and flash chromatographed over silica gel using 6% EtOAc-hexane as eluent. Data of 2d: Colorless oil (747 mg, 85%); [α]_D = -38.21(c 0.28, MeOH). IR (neat): 3020, 1737, 1690, 1413, 1219 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.2 (m, 10 H), 5.8 (m, 1 H), 5.0 (d, J = 12 Hz, 2 H), 4.9 (m, 1 H), 4.8 (m, 2 H), 4.4 (q, 1 H), 3.9 (m, 1 H), 2.8 (d, J = 8.1 Hz, 2 H), 2.3 (m, 1 H), 1.8 (s, 3 H), 1.7 (m, 2 H), 1.5 (m, 2 H), 0.7 (dd, J = 13.7 and 11.8, 1H), -0.011 (s, 6 H). ¹³C NMR (200 MHz, CDCl₃): δ = 170.4, 155.3, 138.9, 136.9, 134.8, 129.8, 128.8, 128.5, 128.4, 128.3, 126.5, 113, 72.7, 67.3, 60.2, 53.8, 37.3, 37.1, 24.5, 23.9, 21.1, -2.4, -2.8. FABMS: m/z = 466 (M + 1), 424.

14

Synthesis of Compound 5a: To a solution of 2d (500 mg, 1.07 mmol) in CH₂Cl₂ (30 mL) at 0 °C were added successively bromine (0.275 mL, 5.3 mmol) and HF-pyridine (1.4 mL). The reaction mixture was stirred at r.t. for 3 h at the end of which excess of HF was destroyed by pouring the mixture over basic alumina. The resulting slurry was diluted with CH₂Cl₂ and filtered. The filtrate was dried over anhyd Na₂SO₄ and concentrated in vacuum. The material thus obtained was dissolved in a mixture of anhyd THF-MeOH (15 mL each) and KHCO₃ (215 mg, 2.15 mmol), KF (124 mg, 2.15 mmol), 30% H₂O₂ (2.68 mL, 21.5 mmol) were added successively to the soln under stirring. The resulting mixture was stirred at r.t. for 10 h, sodium thiosulphate solution (30%, 25 mL) was added to it and the quenched mixture was extracted with EtOAc (50 mL × 3). Combined organic layer was washed with brine (30 mL), dried over anhyd Na₂SO₄, concentrated in vacuo and flash chromatographed over silica-gel using 30% EtOAc-hexane as eluent. Data of 5a: Colorless oil (286 mg, 70%); [α]_D =
-40.54 (c 0.259, MeOH). IR(neat): 3350, 3017, 2935, 1679, 1414 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.2 (m, 10 H), 5.1 (d, J = 12.5 Hz, 2 H), 4.4 (m, 1 H), 4.0 (m, 1 H), 3.6 (m, 3 H), 2.8 (d, J = 6 Hz, 2 H), 2.3 (m, 1 H), 1.9 (s, 3 H), 1.7 (m, 1 H). ¹³C NMR (200 MHz, CDCl₃): δ = 170.4, 156.1, 138.4, 136.2, 129.7, 128.9, 128.6, 126.7, 72.0, 68.1, 67.2, 60.7, 58.9, 36.7, 31.7,21.0. FABMS: m/z = 384 (M + 1), 340, 248. Data of 5b: Colorless oil (54.7 mg, 15%); [α]_D = -65.71 (c 0.035, MeOH). IR(neat): 3366, 2929, 1686, 1413 cm^{- 1}. ¹H NMR (200 MHz, CDCl₃): δ = 7.2 (m, 10 H), 5.0 (d, J = 12.2 Hz, 2 H), 4.1 (M, 1 H), 4.0 (m, 2 H), 3.9 (dd, J = 11.2 and 3.7 Hz, 1 H), 3.6 (dd, J = 11.2 and 3.7 Hz, 1 H), 3.0 (dd, J = 12.6 and 9.8 Hz, 2 H), 2.2 (m, 1 H), 1.8 (d, J = 13.7 Hz, 1 H), 1.7 (bs, 2 H). ¹³C NMR (200 MHz, CDCl₃): δ = 157.3, 139.6, 136.5, 129.9, 128.9, 128.7, 128.6, 126.5, 70.7, 67.8, 65.5, 60.2, 58.9, 36.4, 35.0; FABMS: m/z 342 (M + 1), 298.

15

Synthesis of Compound 6: To a stirred solution of oxalylchloride (0.06 mL, 0.83 mmol) in CH₂Cl₂ (10 mL) at -78 °C under N₂ atmosphere was added DMSO (0.1 mL, 1.14 mmol) using a micro syringe. After stirring the mixture for 30 min, a solution of 5a (200 mg, 0.52 mmol) in CH₂Cl₂ (2 mL) was added slowly over a period of 10 min. The reaction mixture was stirred for 30 min at -78 °C and diisopropylethyl amine (0.455 mL, 2.6 mmol) was added to it slowly in 10 min. The cooling was discontinued and the reaction was allowed to warm to r.t., diluted with CH₂Cl₂ (20 mL), washed with 5% HCl (20 mL), brine and water. The organic layer was dried over anhyd Na₂SO₄, concd under reduced pressure, and flash chromatographed over silica gel using 25% EtOAc-hexane as eluent to give 6 as viscous oil. Data of 6: Colourless oil (119 mg, 60%); [α]_D = -69.23 (c 0.156, MeOH). IR(neat): 2932, 1740, 1712, 1589, 1224
cm^{- 1}. ¹H NMR (200 MHz, CDCl₃): δ = 9.5 (br s, 1 H) 7.2 (m, 10 H), 5.0 (d, J = 12 Hz, 2 H), 4.3 (m, 3 H), 2.7 (dd, J = 13.6 and 9.5 Hz, 2 H), 2.1 (m, 2 H), 1.9 (s, 3 H). ¹³C NMR (200 MHz, CDCl₃): δ = 200.5, 169.9, 158, 138, 136.2, 129.6, 129, 128.8, 126.9, 72.7, 68.1, 64.4, 55.8, 33.0, 23.2, 21.1. FABMS: m/z = 382 (M + 1), 352, 248.