Synthesis of the C1-C11 Segment of Tedanolide via Vinylogous Mukaiyama Aldol Reaction

Abstract

The successful construction of complex natural products depends to a large extent on how efficiently key intermediates can be generated. Here we report our efforts towards the first total synthesis of tedanolide (1), employing Evans’ aldol methodology in combination with a vinylogous Mukaiyama aldol reaction (VMAR) and Sharpless’ asymmetric dihydroxylation. This protocol allows for rapid access to its numerous chiral centers.

Key words

aldol reactions - Mukaiyama - natural products - dihydroxylations - stereoselective synthesis

References

• 1 Tedanolide was isolated from Tedanis ignis: Schmitz FJ. Gunasekera SP. Yalamanchili G. Hossain MB. van der Helm D. J. Am. Chem. Soc.  1984,  106:  7251 
• 2 13-Deoxytedanolide was isolated from Mycale adhaerens: Fusetani N. Sugawara T. Matsunaga S. Hirota H. J. Org. Chem.  1991,  56:  4971 
• 3a Matsushima T. Horita K. Nakajima N. Yonemitsu O. Tetrahedron Lett.  1996,  37:  385 
• 3b Matsushima T. Mori M. Nakajima N. Maeda H. Uenishi J. Yonemitsu O. Chem. Pharm. Bull.  1998,  46:  1335 
• 3c Liu J.-F. Abiko A. Pei Z. Buske DC. Masamune S. Tetrahedron Lett.  1998,  39:  1873 
• 3d Taylor RE. Ciavarri JP. Hearn BR. Tetrahedron Lett.  1998,  39:  9361 
• 3e Roush WR. Lane GC. Org. Lett.  1999,  1:  95 
• 3f Matsushima T. Mori M. Zheng B.-Z. Maeda H. Nakajima N. Uenishi J. Yonemitsu O. Chem. Pharm. Bull.  1999,  47:  308 
• 3g Jung ME. Karama U. Marquez R. J. Org. Chem.  1999,  64:  663 
• 3h Matsushima T. Zheng B.-Z. Maeda H. Nakajima N. Uenishi J. Yonemitsu O. Synlett  1999,  780 
• 3i Smith AB. Lodise SA. Org. Lett.  1999,  1:  1249 
• 3j Zheng B.-Z. Maeda H. Mori M. Kusaka S.-I. Yonemitsu O. Matsushima T. Nakajima N. Uenishi J. Chem. Pharm. Bull.  1999,  47:  1288 
• 3k Jung ME. Marquez R. Tetrahedron Lett.  1999,  40:  3129 
• 3l Matsushima T. Nakajima N. Zheng B.-Z. Yonemitsu O. Chem. Pharm. Bull.  2000,  48:  855 
• 3m Zheng B.-Z. Yamauchi M. Dei H. Kusaka S.-I. Matsui K. Yonemitsu O. Tetrahedron Lett.  2000,  41:  6441 
• 3n Zheng B.-Z. Yamauchi H. Dei H. Yonemitsu O. Chem. Pharm. Bull.  2000,  48:  1761 
• 3o Jung ME. Marquez R. Org. Lett.  2000,  2:  1669 
• 3p Jung ME. Lee CP. Org. Lett.  2001,  3:  333 
• 3q Loh T.-P. Feng L.-C. Tetrahedron Lett.  2001,  42:  6001 
• 3r Loh T.-P. Feng L.-C. Tetrahedron Lett.  2001,  42:  3223 
• 3s Matsui K. Zheng B.-Z. Kusaka S.-I. Kuroda M. Yoshimoto K. Yamada H. Yonemitsu O. Eur. J. Org. Chem.  2001,  3615 
• 3t Hearn BR. Ciavarri JP. Taylor RE. Org. Lett.  2002,  4:  2953 
• 4 Roush WR. Bannister TD. Wendt MD. Jablonowski JA. Scheidt KA. J. Org. Chem.  2002,  67:  4275 
• 5a Christmann M. Bhatt U. Quitschalle M. Claus E. Kalesse M. Angew. Chem. Int. Ed.  2000,  39:  4364 ; Angew. Chem. 2000, 112, 4535
• 5b Christmann M. Bhatt U. Quitschalle M. Claus E. Kalesse M. J. Org. Chem.  2001,  66:  1885 
• 6a Christmann M. Kalesse M. Tetrahedron Lett.  2001,  42:  1269 
• 6b Hassfeld J. Christmann M. Kalesse M. Org. Lett.  2001,  3:  3561 
• 6c Hassfeld J. Kalesse M. Tetrahedron Lett.  2002,  43:  5093 
• 7 Hoffmann RW. Weidmann U. Chem. Ber.  1985,  118:  3980 

8

Aldehyde 11 (92 mg, 0.218 mmol) dissolved in diethyl ether (2 mL) was cooled to -78 °C under an argon atmosphere. Tris(pentafluorophenyl)borane (110 mg, 0.217 mmol) was added and a mixture of ketene acetal 12 (100 mg, 0.438 mmol) and isopropyl alcohol (17 µL, 0.24 mmol) dissolved in diethyl ether (1 mL) was added via syringe pump over 6 h. An additional equivalent of ketene acetal 12 (100 mg, 0.438 mmol) was added in diethyl ether (1 mL) over 4 h. After complete addition, the reaction was quenched by sat. aq NaHCO₃ (2 mL), slowly warmed to r.t. and stirred overnight. Water (3 mL) was added and the mixture was extracted with ether (2 × 15 mL). The organic layer was separated, dried with MgSO₄ and evaporated in vacuo. Flash column chromatography using petroleum ether/ethyl acetate (4:1) as eluent afforded 13 (73 mg, 62%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.21 (d, J = 8.78 Hz, 2 H), 6.85 (d, J = 8.78 Hz, 2 H), 6.70 (dd, J = 15.69, 9.29 Hz,
1 H), 5.80 (dd, J = 15.69, 0.75 Hz, 1 H), 5.16 (d, J = 9.54 Hz, 1 H), 4.38 (s, 2 H), 3.87 (d, J = 7.44 Hz, 1 H), 3.77 (s,
3 H), 3.70 (s, 3 H), 3.28 (dd, J = 8.90, 5.90 Hz, 1 H), 3.28-3.24 (m, 1 H), 3.18 (dd, J = 8.90, 8.03 Hz, 1 H), 2.77-2.66 (m, 1 H), 2.44-2.36 (m, 2 H), 1.59-1.51 (m, 1 H), 1.53 (d, J = 1.25 Hz, 3 H), 0.97 (d, J = 6.52 Hz, 3 H), 0.90 (d, J = 6.77 Hz, 3 H), 0.85 (d, J = 6.90 Hz, 3 H), 0.85 (s, 9 H), 0.02 (s, 3 H), -0.05 (s, 3 H); ¹³C NMR (100 MHz, CDCl₃):
δ = 166.9, 159.2, 151.0, 136.2, 130.8, 130.3, 129.2, 120.7, 113.8, 82.4, 75.1, 72.7, 55.2, 51.4, 40.8, 39.7, 32.5, 26.9, 25.9, 18.1, 17.1, 16.7, 11.9, 8.1, -4.4, -5.1; HRMS calcd for C₃₀H₅₀O₆Si: 534.3377. Found: 534.3371.