Substituted cis-Hydrindan-4-ones by Sequential Cycloadditions

Abstract

The synthesis of substituted cis-hydrindan-4-ones is reported. Particular emphasis was placed on the diastereoselective construction of quaternary stereogenic ring carbon atoms. An intermolecular asymmetric Al(III)-promoted (4+2)-cycloaddition served as the principal C/C-connecting tool. Opportunities for the further structural elaboration of the (4+2)-cycloadducts were explored.

Key words

cycloaddition - Diels–Alder reaction - Lewis acids - ring opening - Grignard reaction

• References

• 1a Butt L, Schnabel C, Hiersemann M. Synthesis 2015; 47: 1922
• 1b Tymann D, Klüppel A, Hiller W, Hiersemann M. Org. Lett. 2014; 16: 4062
• 1c Butt L, Hiersemann M. Synthesis 2014; 46: 3110
• 1d Jaschinski T, Hiersemann M. Org. Lett. 2012; 14: 4114
• 1e Schnabel C, Sterz K, Müller H, Rehbein J, Wiese M, Hiersemann M. J. Org. Chem. 2011; 76: 512
• 1f Nelson B, Hiller W, Pollex A, Hiersemann M. Org. Lett. 2011; 13: 4438
• 1g Schnabel C, Hiersemann M. Org. Lett. 2009; 11: 2555
• 1h Helmboldt H, Hiersemann M. J. Org. Chem. 2009; 74: 1698
• 1i Helmboldt H, Köhler D, Hiersemann M. Org. Lett. 2006; 8: 1573
• 1j Pollex A, Hiersemann M. Org. Lett. 2005; 7: 5705
• 2a Rho J.-R, Lee H.-S, Sim CJ, Shin J. Tetrahedron 2002; 58: 9585
• 2b Jang KH, Jeon J.-e, Ryu S, Lee H.-S, Oh K.-B, Shin J. J. Nat. Prod. 2008; 71: 1701

For selected examples for intermolecular (4+2)-cycloaddition for the synthesis of cis-hydrindanes in general, see:
• 3a Lebold TP, Gallego GM, Marth CJ, Sarpong R. Org. Lett. 2012; 14: 2110
• 3b Wang C, Wang D, Gao S. Org. Lett. 2013; 15: 4402
• 3c Zhang Y, Danishefsky SJ. J. Am. Chem. Soc. 2010; 132: 9567

With 2-siloxy-1,3-dienes in particular, see:
• 3d Jung ME, Ho DG. Org. Lett. 2007; 9: 375
• 3e Jung ME, Guzaev M. Org. Lett. 2012; 14: 5169
• 3f Eagan JM, Hori M, Wu J, Kanyiva KS, Snyder SA. Angew. Chem. Int. Ed. 2015; 54: 7842

For an early report on the synthesis and Diels−Alder reactivity of 5, see:
• 4a Orban J, Turner JV. Tetrahedron Lett. 1983; 24: 2697

For further examples of 5 in (4+2)-cycloadditions, see:
• 4b Ohkata K, Lee YG, Utsumi Y, Ishimaru K, Akiba K. J. Org. Chem. 1991; 56: 5052
• 4c Hongo H, Iwasa K, Kabuto C, Matsuzaki H, Nakano H. J. Chem. Soc., Perkin Trans. 1 1997; 1747
• 5 Jung ME, Ho D, Chu HV. Org. Lett. 2005; 7: 1649
• 6 Henderson JR, Parvez M, Keay BA. Org. Lett. 2009; 11: 3178
• 7 Maugel N, Mann FM, Hillwig ML, Peters RJ, Snider BB. Org. Lett. 2010; 12: 2626
• 8 For the MeAlCl₂-promoted exo diastereoselective (4+2)-cy­cloaddition between an acyclic diene and a chiral (X _SiPr) N-acryloyl oxazolidinone, see: Roush WR, Limberakis C, Kunz RK, Barda DA. Org. Lett. 2002; 4: 1543
• 9 Waldmann has reported the Et₂AlCl-promoted (4+2)-cycloaddition between tiglic aldehyde and diene 11b in toluene (−20 to 5 °C) to proceed with a diastereoselectivity of endo/exo = 84:16 (68%); the dr improved upon deployment of EtAlCl₂•THF in CH₂Cl₂ at −78 °C to endo/exo = 99:1 (81%), see: Brohm D, Waldmann H. Tetrahedron Lett. 1998; 39: 3995
• 10 A completely exo diastereoselective (4+2)-cycloaddition between the diene 11b and an elaborated enone promoted by EtAlCl₂ (1.5 equiv) and THF (1 equiv) in CH₂Cl₂ at r.t. was revealed by Danishefsky, see: Yoon T, Danishefsky SJ, de Gala S. Angew. Chem., Int. Ed. Engl. 1994; 33: 853
• 11 Evans DA, Chapman KT, Bisaha J. J. Am. Chem. Soc. 1988; 110: 1238
• 12 Brown JB, Henbest HB, Jones ER. H. J. Chem. Soc. 1950; 3634
• 13 Reaction of 1-cyclopentene-1-carbaldehyde with decylmagnesium bromide, see: Zhi-Min W, Xin-Hua Q, Wei-Shan Z. Tetrahedron 1990; 46: 1191
• 14 Emde H, Götz A, Hofmann K, Simchen G. Liebigs Ann. Chem. 1981; 1643
• 15 Brønsted acidic impurities triggered the decomposition of diene 5. However, complete recovery was possible after stirring a solution of 5 in CH₂Cl₂ and H₂O (1:1) at r.t. overnight. After Kugelrohr distillation of 5, residual water was removed under fine vacuum conditions at 5 × 10⁻² mbar.
• 16a Brummond KM, Hong S.-p. J. Org. Chem. 2004; 70: 907
• 16b Benzylation using 2-(benzyloxy)-3-nitropyridine according to Mukaiyama was less effective (76%), see: Nakano M, Kikuchi W, Matsuo J.-i, Mukaiyama T. Chem. Lett. 2001; 30: 424
• 17 Evans DA, Bartroli J, Shih TL. J. Am. Chem. Soc. 1981; 103: 2127
• 18 Nemoto H, Satoh A, Fukumoto K, Kabuto C. J. Org. Chem. 1995; 60: 594
• 19 In general, diastereoselectivities were determined by integration of diagnostic ¹H NMR signals. The assignment of the relative configuration rests on the interpretation of NOESY experiments. The absolute configuration of the (4+2)-cycloaddition products is proposed based on the transition-state model depicted in Scheme 6.
• 20 Abad A, Agullo C, Cunat AC, de Alfonso Marzal I, Gris A, Navarro I, Ramirez de Arellano C. Tetrahedron 2007; 63: 1664
• 21 All attempts to remove the auxiliary from benzyl ether (–)-2a were unsuccessful. Application of DIBAL-H or LAH led to the reductive opening of the oxazolidinone and isolation of the corresponding amide. No notable conversion was obtained using various alternative reagents: LiBH₄, NaBH₄, NaOMe, LiOOH, MeOMgBr as well as Me(OMe)NH₂Cl/AlMe₃ or Me(OMe)NH₂Cl/ i-PrMgCl.
• 22 Running the reaction in ethereal solvents or in the presence of more than 0.3 equiv of LAH or DIBAL-H led to the undesired reductive ring-opening of the auxiliary and hydroxy amide formation.
• 23a Brown HC, Krishnamurthy S. J. Am. Chem. Soc. 1972; 94: 7159
• 23b Brown CA. J. Am. Chem. Soc. 1973; 95: 4100
• 24 Miller AE. G, Biss JW, Schwartzman LH. J. Org. Chem. 1959; 24: 627
• 25a Luche JL. J. Am. Chem. Soc. 1978; 100: 2226
• 25b Gemal AL, Luche JL. J. Am. Chem. Soc. 1981; 103: 5454
• 26a Basha A, Lipton M, Weinreb SM. Tetrahedron Lett. 1977; 18: 4171
• 26b Nahm S, Weinreb SM. Tetrahedron Lett. 1981; 22: 3815
• 27a Dess DB, Martin JC. J. Org. Chem. 1983; 48: 4155
• 27b Dess DB, Martin JC. J. Am. Chem. Soc. 1991; 113: 7277
• 28 Paquette LA, Sauer DR, Cleary DG, Kinsella MA, Blackwell CM, Anderson LG. J. Am. Chem. Soc. 1992; 114: 7375
• 29 Furukawa J, Kawabata N, Nishimura J. Tetrahedron 1968; 24: 53
• 30 Kofron WG, Baclawski LM. J. Org. Chem. 1976; 41: 1879
• 31a Miescher K. Helv. Chim. Acta 1946; 29: 743
• 31b Miescher K, Kägi H. Helv. Chim. Acta 1949; 32: 761
• 31c Stahl E, Kaltenbach U. J. Chromatogr. 1961; 5: 351
• 32 Still WC, Kahn M, Mitra A. J. Org. Chem. 1978; 43: 2923
• 33 Gottlieb HE, Kotlyar V, Nudelman A. J. Org. Chem. 1997; 62: 7512