Diastereodivergent Vinylogous Mukaiyama Aldol Reaction

Abstract

The vinylogous Mukaiyama aldol reaction (VMAR) allows the rapid assembly of polyketide building blocks in complex natural product syntheses. Here we describe how different dia­stereomers can be obtained efficiently from commercially available Roche ester.

Key words

vinylogous aldol - Roche ester - Mukaiyama - polyketides - substrate control

• References and Notes

• 1a Fuson RC. Chem. Rev. 1935; 16: 1
• 1b Casiraghi G, Battistini L, Curti C, Rassu G, Zanardi F. Chem. Rev. 2011; 111: 3076
• 2a Kalesse M. Top. Curr. Chem. 2005; 244: 43
• 2b Denmark SE, Heemstra JR. Jr, Beutner GL. Angew. Chem. Int. Ed. 2005; 44: 4682
• 3a Paterson I, Paquet T. Org. Lett. 2010; 12: 2158
• 3b Paterson I, Findlay AD, Florence GJ. Tetrahedron 2007; 63: 5806
• 3c Evans DA, Burch JD, Hu E, Jaeschke G. Tetrahedron 2008; 64: 4671
• 3d Schäckel R, Hinkelmann B, Sasse F, Kalesse M. Angew. Chem. Int. Ed. 2010; 49: 1619
• 3e Brodmann T, Lorenz M, Schäckel R, Simsek S, Kalesse M. Synlett 2009; 174
• 3f Ehrlich G, Hassfeld J, Eggert U, Kalesse M. Chem. Eur. J. 2008; 14: 2232
• 3g Liesener FP, Jannsen U, Kalesse M. Synthesis 2006; 2590
• 3h Ehrlich G, Kalesse M. Synlett 2005; 655
• 3i Schmauder A, Müller S, Maier ME. Tetrahedron 2008; 64: 6263
• 3j Jiang X, Liu B, Lebreton S, De Brabander JK. J. Am. Chem. Soc. 2007; 129: 6386
• 4a Hassfeld J, Kalesse M. Tetrahedron Lett. 2002; 43: 5093
• 4b Christmann M, Kalesse M. Tetrahedron Lett. 2001; 42: 1269
• 5a Hassfeld J, Eggert U, Kalesse M. Synthesis 2005; 1183
• 5b Hassfeld J, Kalesse M. Synlett 2002; 2007
• 5c Hassfeld J, Christmann M, Kalesse M. Org. Lett. 2001; 3: 3561
• 6 Stanton GR, Kauffman MC, Walsh PJ. Org. Lett. 2012; 14: 3368
• 7 For the use of Cy₂BCl in enol formation, see: Brown HC, Dhar RK, Bakshi RK, Pandiarajan PK, Singaram B. J. Am. Chem. Soc. 1989; 111: 3441
• 8 Hoffmann RW, Weidmann U. Chem. Ber. 1985; 118: 3980
• 9 Matsumori N, Kaneno D, Murata M, Nakamura H, Tachibana K. J. Org. Chem. 1999; 64: 866
• 10 Nakamura R, Tanino K, Miyashita M. Org. Lett. 2003; 5: 3579
• 11 Ishii Y, Nagumo S, Arai T, Akuzawa M, Kawahara N, Akita H. Tetrahedron 2006; 62: 716
• 12 Lee JM, Helquist P, Wiest O. J. Am. Chem. Soc. 2012; 134: 14973
• 13 Vinylogous Mukaiyama Aldol Reaction (VMAR); General Procedure: Aldehyde 2 (1 equiv) was dissolved in CH₂Cl₂–Et₂O (9:1, 0.1 M) at –78 °C. The appropriate Lewis acid [and in the case of Zn, isopropanol (1.2 equiv)] was added neat and the mixture was stirred at –78 °C for 10 min. Neat TES-ketene acetal 4 (1.5 equiv) was added slowly and the resulting solution was stirred at –78 °C until the entire aldehyde was consumed (reaction analyzed by TLC). The reaction was quenched by addition of saturated aqueous NaHCO₃ solution, extracted with CH₂Cl₂, and dried over MgSO₄. Concentration in vacuo and silica gel column chromatography (EtOAc–hexanes, 20%) gave the desired isomeric mixture as a colorless oil. The isomers can be differentiated by using the ¹H NMR signal for the olefinic β-position [δ = 7.00 ppm (dd) for 6; δ = 7.09 ppm (dd) for 11; δ = 6.79 ppm (dd) for 12]. 4,5-syn-5,6-anti VMAR 6: ¹H NMR (400 MHz, CDCl₃): δ = 7.25–7.21 (m, 2 H), 7.00 (dd, J = 15.8, 7.7 Hz, 1 H), 6.90–6.86 (m, 2 H), 5.82 (dd, J = 15.8, 1.3 Hz, 1 H), 4.43 (s, 2 H), 3.81 (s, 3 H), 3.72 (s, 3 H), 3.63 (dd, J = 9.2, 3.8 Hz, 1 H), 3.54 (d, J = 4.1 Hz, 1 H), 3.47 (dt, J = 6.9, 4.6 Hz, 2 H), 3.42 (dd, J = 9.2, 6.9 Hz, 1 H), 2.44 (dq, J = 12.7, 6.7 Hz, 1 H), 1.90 (dqd, J = 14.0, 7.0, 3.8 Hz, 1 H), 1.09 (d, J = 6.7 Hz, 3 H), 0.93 (d, J = 7.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.2, 159.5, 152.8, 129.7, 129.5, 120.5, 114.0, 79.0, 74.7, 73.4, 55.4, 51.6, 40.2, 35.8, 14.5, 13.1. HRMS (ESI⁺): m/z [M + Na⁺] calcd for C₁₈H₂₆O₅Na: 345.1678; found: 345.1675. 4,5-anti-5,6-anti VMAR 11: ¹H NMR (400 MHz, CDCl₃): δ = 7.25–7.20 (m, 2 H), 7.09 (dd, J = 15.9, 8.7 Hz, 1 H), 6.90–6.85 (m, 2 H), 5.84 (dd, J = 15.9, 0.9 Hz, 1 H), 4.43 (s, 2 H), 3.80 (s, 3 H), 3.72 (s, 3 H), 3.57 (dd, J = 9.2, 3.8 Hz, 1 H), 3.48–3.39 (m, 2 H), 2.54–2.44 (m, 1 H), 1.92–1.82 (m, 1 H), 1.14 (d, J = 6.9 Hz, 3 H), 0.83 (d, J = 6.9 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.1, 159.5, 150.7, 129.6, 129.6, 121.5, 114.0, 80.0, 75.6, 73.4, 55.4, 51.5, 40.1, 36.4, 17.3, 13.8. HRMS (ESI⁺): m/z [M + Na⁺] calcd for C₁₈H₂₆O₅Na: 345.1678; found: 345.1676. 4,5-syn-5,6-syn VMAR 12: ¹H NMR (400 MHz, CDCl₃): δ = 7.25–7.20 (m, 2 H), 6.90–6.85 (m, 2 H), 6.79 (dd, J = 15.7, 9.3 Hz, 1 H), 5.85 (dd, J = 15.7, 0.8 Hz, 1 H), 4.44 (s, 2 H), 3.81 (s, 3 H), 3.72 (s, 3 H), 3.63 (dd, J = 9.1, 2.0 Hz, 1 H), 3.53 (dd, J = 9.0, 3.9 Hz, 1 H), 3.47 (dd, J = 9.0, 4.8 Hz, 1 H), 2.51–2.40 (m, 1 H), 1.83–1.74 (m, 1 H), 1.15 (d, J = 6.6 Hz, 3 H), 0.95 (d, J = 7.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.1, 159.4, 151.2, 129.6, 129.4, 121.0, 114.0, 77.1, 75.4, 73.3, 55.4, 51.7, 41.0, 36.0, 16.9, 9.9. HRMS (ESI⁺): m/z [M + Na⁺] calcd for C₁₈H₂₆O₅Na: 345.1678; found: 345.1675.