A Stereodivergent Enantioselective Approach to the C5-C8 Segment of Berkelic Acid

Abstract

A catalytic, asymmetric Gosteli-Claisen rearrangement (CAGC) has been utilized to provide the C5-C8 segment of berkelic acid.

Key words

allyl vinyl ether - asymmetric catalysis - berkelic acid - Claisen rearrangement - dithiane

References and Notes

• 1 Stierle AA. Stierle DB. Kelly K. J. Org. Chem.  2006,  71:  5357 
• 2a Nakajima H. Hamasaki T. Maeta S. Kimura Y. Takeuchi Y. Phytochemistry  1990,  29:  1739 
• 2b Nakajima H. Matsumoto R. Kimura Y. Hamasaki T. J. Chem. Soc., Chem. Commun.  1992,  1654 
• 2c Nakajima H. Fujimoto H. Matsumoto R. Hamasaki T. J. Org. Chem.  1993,  58:  4526 
• 2d Nakajima H. Fukuyama K. Fujimoto H. Baba T. Hamasaki T. J. Chem. Soc., Perkin Trans. 1  1994,  1865 
• 3 Buchgraber P. Snaddon TN. Wirtz C. Mynott R. Goddard R. Fürstner A. Angew. Chem. Int. Ed.  2008,  47:  8450 
• 4 Wu X. Zhou J. Snider BB. Angew. Chem. Int. Ed.  2009,  48:  1283 
• 5a Hoekstra R. Eskens FALM. Verweij J. Oncologist  2001,  6:  415 
• 5b Coussens LM. Fingleton B. Matrisian LM. Science  2002,  295:  2387 
• 6 Hu J. Van den Steen PE. Sang Q.-XA. Opdenakker G. Nat. Rev. Drug Discovery  2007,  6:  480 
• 7 McOmie JFW. Turner AB. Tute MS. J. Chem. Soc. C  1966,  1608 
• 8a Inagaki M. Haga N. Kobayashi M. Ohta N. Kamata S. Tsuri T. J. Org. Chem.  2002,  67:  125 
• 8b Zjawiony JK. Bartyzel P. Hamann MT. J. Nat. Prod.  1998,  61:  1502 
• 9 Hiersemann M. Synthesis  2000,  1279 
• 11 Evans DA. Burgey CS. Paras NA. Vojkovsky T. Tregay SW. J. Am. Chem. Soc.  1998,  120:  5824 
• 12a Abraham L. Czerwonka R. Hiersemann M. Angew. Chem. Int. Ed.  2001,  40:  4700 
• 12b Abraham L. Körner M. Schwab P. Hiersemann M. Adv. Synth. Catal.  2004,  346:  1281 
• 12c Abraham L. Körner M. Hiersemann M. Tetrahedron Lett.  2004,  45:  3647 
• For applications of the CAGC in total synthesis, see:
• 12d Pollex A. Hiersemann M. Org. Lett.  2005,  7:  5705 
• 12e Körner M. Hiersemann M. Org. Lett.  2007,  9:  4979 
• 12f Wang Q. Millet A. Hiersemann M. Synlett  2007,  1683 
• 14 Dess DB. Martin JC. J. Org. Chem.  1983,  48:  4155 
• 15 Zhou J. Snider BB. Org. Lett.  2007,  9:  2071 
• 16 Onoe A. Uemura S. Okano M. Bull. Chem. Soc. Jpn.  1974,  47:  2818 
• 17 Dale JA. Mosher HS. J. Am. Chem. Soc.  1973,  95:  512 

10

Preparative HPLC conditions: Nucleosil 50-5; 32 × 237 mm; heptane-EtOAc, 25:1; 26 mL/min; t _R (Z,Z) = 31.5 min, t _R (E,Z) = 38.0 min; baseline separation with 200 mg/injection.

13

The relative and absolute configuration was assigned based on the established stereochemical course of the CAGC. The enantiomeric excess was determined by Mosher ester ^¹H NMR analysis. To synthesize Mosher esters, aldehydes 14 or 18 were reduced to the corresponding primary alcohols with NaBH₄ in methanol, followed by esterification with Mosher’s acid.^¹7

18

α-Keto Ester 6: To a solution of [Cu{(S,S)-tert-Bu-Box}(H₂O)₂](SbF₆)₂ (12; 81 mg, 0.094 mmol, 8 mol%) in CH₂Cl₂ (3 mL, 3 mL/mmol 6) was added (Z,Z)-7 (0.5 g, 1.18 mmol, 1 equiv) in CH₂Cl₂ (3 mL, 3 mL/mmol 6) at r.t. The solution was stirred for 24 h, then the solvent was evaporated and the residue filtered through a short plug of silica gel (cyclohexane-EtOAc, 1:1). Evaporation of the solvent and purification by flash chromatography (cyclohexane-EtOAc, 50:1→20:1) furnished 6 (478 mg, 96%) as a clear oil. R _f  = 0.34 (cyclohexane-EtOAc, 10:1); ^¹H NMR (CDCl₃, 400 MHz): δ = 7.62-7.64 (m, 4 H), 7.36-7.45 (m, 6 H), 5.81 (ddd, J = 8.7, 10.3, 17.3 Hz, 1 H), 5.00-5.08 (m, 2 H), 3.80 (s, 3 H), 3.65-3.67 (m, 2 H), 3.56-3.63 (m, 1 H), 2.67-2.73 (m, 1 H), 1.11 (d, J = 6.8 Hz, 3 H), 1.04 (s, 9 H); ^¹³C NMR (CDCl₃, 100 MHz): δ = 196.7 (C), 161.8 (C), 136.8 (CH), 135.6 (4 × CH), 133.3 (C), 133.1 (C), 129.7 (2 × CH), 127.6 (4 × CH), 117.5 (CH₂), 64.1 (CH₂), 52.7 (CH₃), 48.3 (CH), 42.6 (CH), 26.7 (3 × CH₃), 19.2 (C), 12.5 (CH₃); IR (neat): 2930, 2860, 1730, 1430 cm^-¹; Anal. Calcd for C₂₅H₃₂O₄Si: C, 70.72; H, 7.60. Found: C, 70.6; H, 7.6; [α]^²5 _D +38.1 (c 1.0, CHCl₃).
α-Keto Ester 19: To a solution of [Cu{(S,S)-tert-Bu-Box}(H₂O)₂](SbF₆)₂ (12, 384 mg, 0.44 mmol, 8 mol%) in CF₃CH₂OH (11 mL, 2 mL/mmol 7) was added (Z,Z)-7 (2.36 g, 5.55 mmol, 1 equiv) in CH₂Cl₂ (17 mL, 3 mL/mmol 7) at r.t. The solution was stirred for 24 h, then the solvent was evaporated and the residue filtered through a short plug of silica gel (cyclohexane-EtOAc, 1:1). Evaporation of the solvent and purification by flash chromatography (cyclohexane-EtOAc, 50:1→20:1) furnished 19 (2.24 g, 95%) as a clear oil. R _f  = 0.34 (cyclohexane-EtOAc, 10:1); ^¹H NMR (CDCl₃, 400 MHz): δ = 7.62-7.64 (m, 4 H), 7.36-7.45 (m, 6 H), 5.54 (ddd, J = 17.1, 10.4, 9.3 Hz, 1 H), 4.98-5.08 (m, 2 H), 3.80 (s, 3 H), 3.57-3.66 (m, 3 H), 2.75-2.83 (m, 1 H), 1.03-1.07 (m, 12 H); ^¹³C NMR (CDCl₃, 100 MHz): δ = 196.6 (C), 161.7 (C), 135.5 (4 × CH), 135.0 (CH), 133.2 (C), 133.1 (C), 129.7 (2 × CH), 127.6 (4 × CH), 118.5 (CH₂), 65.3 (CH₂), 52.7 (CH₃), 48.0 (CH), 42.4 (CH), 26.7 (3 × CH₃), 19.2 (C), 12.4 (CH₃); IR (neat): 2930, 2860, 1730, 1430 cm^-¹; Anal. Calcd for C₂₅H₃₂O₄Si: C, 70.72; H, 7.60. Found: C, 70.8; H, 7.5; [α]^²5 _D +4.3 (c 0.99, CHCl₃).
Ketone 5: To a solution of 15 (1.1 g, 2.87 mmol, 1 equiv) in CH₂Cl₂ (5.7 mL, 2 mL/mmol) was added pyridine (0.91 g, 11.5 mmol, 4.0 equiv) and Dess-Martin periodinane (1.6 g, 3.8 mmol, 1.3 equiv). The white suspension was stirred at r.t. for 5 h before being quenched with sat. Na₂S₂O₃. The phases were separated, and the aqueous phase was washed with CH₂Cl₂. The combined organic layers were dried (MgSO₄), concentrated under reduced pressure and the crude product was purified by flash chromatography (cyclohexane-EtOAc, 20:1) to yield 5 (0.98 g, 89%) as a colorless oil. R _f  = 0.27 (cyclohexane-EtOAc, 20:1); ^¹H NMR (CDCl₃, 400 MHz): δ = 7.64-7.66 (m, 4 H), 7.37-7.45 (m, 6 H), 5.77-5.86 (m, 1 H), 5.00-5.08 (m, 2 H), 3.67 (d, J = 5.2 Hz, 2 H), 2.82 (m, 1 H), 2.43-2.49 (m, 1 H), 2.12 (s, 3 H), 1.04-1.05 (m, 12 H); ^¹³C NMR (CDCl₃, 100 MHz): δ = 211.8 (C), 137.7 (4 × CH), 135.6 (CH), 133.4 (2 × C), 129.7 (2 × CH), 127.6 (4 × CH), 116.9 (CH₂), 64.3 (CH₂), 48.6 (CH), 47.6 (CH), 29.4 (CH₃), 26.8 (3 × CH₃), 19.3 (C), 13.7 (CH₃); IR (neat): 2960, 2858, 1713, 1428 cm^-¹; Anal. Calcd for C₂₄H₃₂O₂Si: C, 75.74; H, 8.47. Found: C, 75.6; H, 8.3; [α]^²5 _D +31.8 (c 0.97, CHCl₃).
Acetal 17: To a solution of 22 (106 mg, 0.23 mmol, 1 equiv) in THF (2 mL, 8.6 mL/mmol) and HMPA (0.3 mL), was added t-BuLi (0.16 mL, 0.26 mmol, 1.1 equiv, 1.6 M in pentane) at -78 ˚C. The solution was stirred at -78 ˚C for 15 min before a solution of iodoacetaldehyde dimethyl acetal (150 mg, 0.69 mmol, 3.0 equiv) and LiI (109 mg, 0.81 mmol, 3.5 equiv) in THF (1 mL) was added. After stirring for 30 min, the reaction mixture was diluted with sat. NaHCO₃ and extracted with CH₂Cl₂. The combined organic layers were dried (MgSO₄) and concentrated under reduced pressure and the crude product was purified by flash chromatography (cyclohexane-EtOAc, 50:1→20:1) to afford unreacted 22 (20 mg, 19%) and 17 (77 mg, 61%). R _f  = 0.20 (cyclohexane-EtOAc, 20:1); ^¹H NMR (CDCl₃, 400 MHz): δ = 7.68-7.70 (m, 4 H), 7.38-7.45 (m, 6 H), 5.69-5.78 (m, 1 H), 5.06-5.17 (m, 2 H), 4.81 (t, J = 4.0 Hz, 1 H), 3.56-3.57 (m, 2 H), 3.30-3.40 (m, 7 H), 2.72-3.03 (m, 3 H), 2.62-2.69 (m, 1 H), 2.51-2.57 (m, 1 H), 2.18-2.22 (m, 1 H), 1.78-1.98 (m, 3 H), 1.05-1.10 (m, 12 H). ^¹³C NMR (CDCl₃, 100 MHz): δ = 136.7 (CH), 135.6 (4 × CH), 133.6 (C), 133.5 (C), 129.6 (2 × CH), 127.6 (4 × CH), 118.1 (CH₂), 102.7 (CH), 66.8 (CH₂), 57.2 (C), 53.5 (CH₃), 52.5 (CH₃), 46.0 (CH), 39.5 (CH₂), 35.8 (CH), 26.9 (3 × CH₃), 25.8 (CH₂), 25.5 (CH₂), 24.5 (CH₂), 19.3 (C), 9.9 (CH₃); IR (neat): 2930, 2900, 2860, 1430 cm^-¹; Anal. Calcd for C₃₀H₄₄O₃S₂Si: C, 66.13; H, 8.14. Found: C, 66.2; H, 8.1; [α]^²5 _D +21.0 (c 1.01, CHCl₃).