First Enantioselective Total Synthesis of the Reported Structure of (R)-(+)-Orizaterpenyl Benzoate Using an Asymmetric Allylation of a Prochiral Ketone in a Domino Process

Abstract

An efficient synthesis of (R)-orizaterpenyl benzoate ­using a multicomponent domino allylation reaction of a prochiral ketone with allyltrimethyl silane and the enantiopure silyl ether of benzyl phenyl carbinol in the presence of catalytic amounts of TfOH is described.

Key words

allylsilane - asymmetric allylation - domino reactions - natural products - ozonolysis - tertiary homoallylic alcohols

References and Notes

• 1 Chung IM. Ali M. Hahn SJ. Siddiqui NA. Lim YH. Ahmad A. Chem. Nat. Comp.  2005,  41:  182 
• 2 Tietze LF. Kinzel T. Brazel C. Acc. Chem. Res.  2009,  42:  367 
• 3 Tietze LF. Kinzel T. Wolfram T. Chem. Eur. J.  2009,  15:  6199 
• 4a Tietze LF. Kinzel T. Schmatz S. J. Am. Chem. Soc.  2008,  130:  4386 
• 4b Tietze LF. Schmatz S. Kinzel T.
  J. Am. Chem. Soc.  2006,  128:  11483 
• 5a Tietze LF. Dölle A. Schiemann K. Angew. Chem. Int. Ed.  1992,  31:  1372 ; Angew. Chem. 1992, 104, 1366
• 5b Tietze LF. Schiemann K. Wegner C. J. Am. Chem. Soc.  1995,  117:  5851 
• 5c Tietze LF. Wegner C. Wulff C. Synlett  1996,  471 
• 5d Tietze LF. Wegner C. Wulff C. Eur. J. Org. Chem.  1998,  1639 
• 5e Tietze LF. Weigand B. Völkel L. Wulff C. Bittner C. Chem. Eur. J.  2001,  7:  161 
• 5f Tietze LF. Völkel L. Wulff C. Weigand B. Bittner C. McGrath P. Johnson K. Schäfer M. Chem. Eur. J.  2001,  7:  1304 
• 5g Tietze LF. Hölsken S. Adrio J. Kinzel T. Wegner C. Synthesis  2004,  2236 

6

Chung et al. reported a value of [α]_D ^²0 +1.6 (CHCl₃) and proposed the S configuration at the stereogenic center without giving an explanation. Moreover, the spectroscopic data of the synthesised material do not match the data of the isolated compound. Unfortunately, neither a sample nor copies of the original spectra could be provided by Chung et al. on our request for comparison.

7

(4 R ,1′ R )-4,8-Dimethyl-4-(1,2-diphenylethoxy)nonene (5): To a stirred solution of the (R)-trimethylsilyl ether 4 (404 mg, 1.50 mmol, 1.0 equiv), ketone 2 (192 mg, 1.50 mmol, 1.0 equiv) and allyltrimethyl silane (171 mg, 1.50 mmol, 1.0 equiv) in anhyd CH₂Cl₂ (10 mL) was slowly added precooled TfOH (30 µL, 0.30 mmol, 0.2 equiv) at -78 ˚C. After stirring for 15 h at this temperature the reaction was quenched by adding Et₃N (0.2 mL, 1.43 mmol, 0.8 equiv), the solvent was evaporated and the residue was resolved in THF (10 mL). To this solution TBAF (200 mg, 0.75 mmol, 0.5 equiv) was added at r.t. and the mixture was stirred for another 2 h. Then the solution was filtered through a short pad of Celite, which was washed with MTBE. After evaporation of the solvents, the crude product was purified by column chromatography on silica gel (n-pentane-MTBE, 50:1) to obtain a mixture of the diastereomeric homoallylic ethers 5a and 5b (446 mg, 1.30 mmol) in 85% yield with a ratio of 90:10 as a colourless oil; [α]_D ^²0 +19.0 (c = 0.67, CHCl₃). Major diastereomer 5a: ^¹H NMR (300 MHz, CDCl₃): δ = 0.82 (d, J = 6.6 Hz, 3 H), 0.83 (d, J = 6.6 Hz, 3 H), 0.83 (s, 3 H), 0.89-1.08 (m, 2 H), 1.10-1.32 (m, 4 H), 1.43 (non, J = 6.6 Hz, 1 H), 2.06 (dd, J = 14.9, 7.2 Hz, 1 H), 2.13 (dd, J = 14.9, 7.2 Hz, 1 H), 2.85 (dd, J = 13.2, 5.8 Hz, 1 H), 2.99 (dd, J = 13.2, 7.6 Hz, 1 H), 4.63 (dd, J = 7.6, 5.8 Hz, 1 H), 4.89-5.00 (m, 2 H), 5.68 (ddt, J = 15.9, 11.2, 7.2 Hz, 1 H), 7.09 (dd, J = 7.8, 1.6 Hz, 2 H), 7.17-7.31 (m, 8 H). ^¹³C NMR (150 MHz, CDCl₃): δ = 21.3, 22.6, 22.7, 23.7, 27.9, 39.4, 39.6, 43.5, 47.0, 75.5, 78.1, 116.7, 125.9, 126.4 (2 × C), 126.7, 127.8 (2 × C), 127.8 (2 × C), 130.0 (2 × C), 135.0, 138.8, 145.6. Minor diastereomer 5b (showing distinguishable signals): ^¹H NMR (300 MHz, CDCl₃): δ = 0.87 (d, J = 6.6 Hz, 3 H), 0.88 (d, J = 6.6 Hz, 3 H). ^¹³C NMR (150 MHz, CDCl₃): δ = 21.3, 22.7, 22.7, 23.6, 27.9, 38.9, 39.5, 44.3, 47.1, 75.4. IR (film): 3064, 3028, 2952, 1639, 1603, 1495, 1454, 1377, 1309, 1148, 1059, 912, 757, 699 cm^-¹. UV (MeCN): λ_max (log ε) = 258.5 (2.6408), 253.0 (2.5649), 264.0 (2.5235) nm. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₅H₃₄O: 373.2502; found: 373.2500.
( R )-3-Hydroxy-3,7-dimethyloctyl Benzoate (1): Compound 8 (30 mg, 65 µmol, 1.0 equiv) was hydrogenated in MeOH (5 mL) using a flow reactor (H-CUBE^®) loaded with a 10% Pd/C cartridge and H₂ (80 bar) with a flow rate of 0.3 mL/min. Evaporation of the solvent and purification of the residue by column chromatography on silica gel
(n-pentane-MTBE, 5:1) afforded (R)-orizaterpenyl benzoate (1) (16.2 mg, 58.6 µmol) in 89% yield as a colourless oil; [α]_D ^²0 +1.3 (c = 1, CHCl₃). ^¹H NMR (300 MHz, CDCl₃): δ = 0.84 (d, J = 6.6 Hz, 6 H), 1.08-1.20 (m, 2 H), 1.25 (s, 3 H), 1.28-1.40 (m, 2 H), 1.44-1.52 (m, 2 H), 1.51 (non, J = 6.6 Hz, 1 H), 1.77 (br s, 1 H, OH), 1.92 (dt,
J = 14.3, 6.9 Hz, 1 H), 1.96 (dt, J = 14.3, 6.9 Hz, 1 H), 4.47 (t, J = 6.9 Hz, 2 H), 7.40 (t, J = 7.4 Hz, 2 H), 7.52 (tt, J = 7.4, 1.3 Hz, 1 H), 8.00 (dt, J = 7.4, 1.3 Hz, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.7, 22.6, 22.6, 27.2, 28.0, 39.4, 39.8, 42.9, 61.8, 71.9, 128.2 (2 × C), 129.4 (2 × C), 130.2, 132.8, 166.5. IR (film): 2955, 2931, 1717, 1495, 1460, 1438, 1274, 1246, 1115, 1026, 755 cm^-¹. UV (MeCN): λ_max (log ε) = 259.0 (2.5696), 268.0 (2.5640) nm. HPLC (Chiralcel^® OD, eluent: n-hexane, flow rate: 0.8 mL/min, c = 1 mg/mL, injection volume: 10 µL): t _R = 18 min. For comparison also the racemic mixture of 1 was prepared using a racemic mixture of 4 in the synthesis. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₂₆O₃: 301.1780; found: 301.1775.