ORGANIC LETTERS
Oxazaborolidinone-Promoted Vinylogous Mukaiyama Aldol Reactions
2007 Vol. 9, No. 26 5637-5639
Serkan Simsek, Melanie Horzella, and Markus Kalesse* Institut fu¨r Organische Chemie, Leibniz UniVersita¨t HannoVer, Schneiderberg 1B, 30167 HannoVer, Germany
[email protected] Received November 1, 2007
ABSTRACT
δ-Hydroxy-r,β-unsaturated carbonyl compounds were prepared in one step via the vinylogous Mukaiyama aldol reactions with O,O-silyl ketene acetals. Isopropyl alcohol as additive and tryptophane-based B-phenyloxazaborolidinone were required for obtaining the γ-alkylated product in high enantioselectivities.
The increasing demand for new antibiotics and antitumor compounds led to a growing interest in biologically active compounds. In particular, polyketides proved to be attractive targets for biology-driven research. In this context, the rapid and efficient total synthesis of these natural products becomes increasingly important. Standard strategies for the construction of the polyketide framework parallel the biosynthesis of these compounds where acetate or propionate unites are joined.1 Despite the reliable predictability and broad applicability of aldol or aldol-like reactions, new methods for the rapid access of larger polyketide frameworks could speed up the synthesis of new compounds. With this background, different approaches to install stereoselective variations of the vinylogous Mukaiyama aldol reaction (VMAR) or vinylogous aldol reactions in general have been put forward, providing access to δ-hydroxy-R,βunsaturated esters or lactones.2-4 The vinylogous extension of the aldol reactions is associated with regioselectivity issues since addition to the ketene acetal can proceed in the R- or γ-position (Scheme 1).5 We previously reported the tri(1) (a) Schetter, B.; Mahrwald, R. Angew. Chem., Int. Ed. 2006, 45, 7506. (b) Staunton, J.; Weissman, K. J. Nat. Prod. Rep. 2001, 18, 380. (2) For reviews see: (a) Kalesse, M. Top. Curr. Chem. 2005, 244, 43. (b) Denmark, S. E.; Heemstra, J. R., Jr.; Beutner, G. L. Angew. Chem., Int. Ed. 2005, 44, 4682. (c) Soriente, A.; De Rosa, M.; Villano, R.; Scettri, A. Curr. Org. Chem. 2004, 8, 993. (d) Casiraghi, G.; Zanardi, F.; Appendino, G.; Rassu, G. Chem. ReV. 2000, 100, 1929. 10.1021/ol702640w CCC: $37.00 Published on Web 12/04/2007
© 2007 American Chemical Society
Scheme 1.
Regioselectivity in the VMAR
arylborane-catalyzed VMAR with unsubstituted silyl ketene acetals in high regio- and Felkin selectivities.6 Based on the wide range of applications for the vinylogous Mukaiyama aldol reaction, enantioselective variations became increasingly important, and we envisioned that amino (3) (a) Sato, M.; Sunami, S.; Sugita, Y.; Kaneko, C. Chem. Pharm. Bull. 1994, 42, 839. (b) Sato, M.; Sunami, S.; Sugita, Y.; Kaneko, C. Heterocycles 1995, 41, 1435. (c) Singer, R. A.; Carreira, E. M. J. Am. Chem. Soc. 1995, 117, 12360. (d) Evans, D. A.; Murry, J. A.; Kozlowski, M. C. J. Am. Chem. Soc. 1996, 118, 5814. (e) Kru¨ger, J.; Carreira, E. M. J. Am. Chem. Soc. 1998, 120, 837. (f) Bluet, G.; Campagne, J. M. Tetrahedron Lett. 1999, 40, 5507. (g) Denmark, S. E.; Beutner, G. L. J. Am. Chem. Soc. 2003, 125, 7800. (h) Denmark, S. E.; Heemstra, J. R., Jr. Synlett 2004, 2411. (i) Gondi, V. B.; Gravel, M.; Rawal, V. H. Org. Lett. 2005, 7, 5657. (j) Moreau, X.; Bazan-Tejeda, B.; Campagne, J.-M. J. Am. Chem. Soc. 2005, 127, 7288. (k) Re´my, P.; Langner, M.; Bolm, C. Org. Lett. 2006, 8, 1209. (l) Denmark, S. E.; Heemstra, J. R., Jr. J. Am. Chem. Soc. 2006, 128, 1038. (m) Denmark, S. E.; Heemstra, J. R., Jr. J. Org. Chem. 2007, 72, 5668. (n) Heumann, L. V.; Keck, G. E. Org. Lett. 2007, 9, 4275.
Table 1. Enantioselective VMAR with Isobutyraldehyde and Ketene Acetal 1 Catalyzed by OXBa
γ-product 2 entrya
OXB (mol %)
1 2 3 4b 5b 6b 7b,f 8b,f 9b,f
3 (20/100) 4 (20/100) 5 (20/100) 3 (20) 4 (20) 5 (20) 5 (20) 5 (50) 5 (100)
additive
γ/R
yieldc,d (%)
eee (%)
i-PrOH i-PrOH i-PrOH i-PrOH i-PrOH i-PrOH
99:
