Novel Stereocontrolled Synthesis of Highly Functionalized Cyclobutanes by Epoxide Opening through a Carbanion Intermediate in Heteroconjugate Addition

Abstract

We have demonstrated a new cyclobutane ring formation from the trans-1,2-disubstituted epoxides through intramolecular carbanion opening process. In this reaction, the nucleophilic carb­anion is generated not via α-proton abstraction but via heteroconjugate addition. These studies indicate that the different configuration of each epoxide (syn and anti) do not affect its reactivity and the reaction velocity in the cyclization step, providing multifunctionalized cyclobutanes in a regio- and stereospecific manner.

Key words

heteroconjugate addition - sulfonyl carbanion - epoxides - cyclization - cyclobutanes

References and Notes

• 1a Grandisol is a histrical example of pheromone having a cyclobutane moiety, see: Petschen I. Parrilla A. Bosch MP. Amela C. Botar AA. Camps F. Guerreo A. Chem. Eur. J.  1999,  5:  3299 
• 1b Solanoeclepin may be another example having three-, four-, five-, six-, and seven-membered rings including cyclobutane moiety of fully functional groups, see: Schenk H. Driessen RAJ. de Gelder R. Goubitz K. Nieboer H. Brüggemann-Rotgans IEM. Diepenhorst P. Croat. Chem. Acta  1999,  72:  593 
• For recent reviews on application of cyclobutane, see:
• 2a Bellus D. Ernst B. Angew. Chem., Int. Ed. Engl.  1988,  27:  797 
• 2b Lee-Ruff E. Mladenova G. Chem. Rev.  2003,  103:  1449 
• 2c Namyslo JC. Kaufmann DE. Chem. Rev.  2003,  103:  1485 
• 2d Sadana AK. Saini RK. Billups WE. Chem. Rev.  2003,  103:  1539 
• 3 Ciamician G. Silber P. Ber. Dtsch. Chem. Ges.  1908,  41:  1928 
• For recent reviews on [2+2] photocycloaddition, see:
• 4a Demuth M. Mikhail G. Synthesis  1989,  145 
• 4b Bach T. Synthesis  1998,  683 
• 5a Roberts JD. Sharts CM. Org. React.  1962,  12:  1 
• 5b Crimmins MT. Reinhold TL. Org. React.  1993,  44:  297 
• 5c Arseniyadis S. Kyler KS. Watt DS. Org. React.  1984,  31:  1 
• 6a Vogel E. Müller K. Liebigs. Ann. Chem.  1958,  615:  29 
• 6b Ghosez L. Montaigne R. Roussel A. Vanlierde H. Mollet P. Tetrahedron  1971,  27:  615 
• 7a Wenkert E. Bakuzis P. Baumgarten RJ. Leicht CL. Schenk HP. J. Am. Chem. Soc.  1971,  93:  3208 
• 7b Schumacher W. Hanack M. Synthesis  1981,  490 
• 7c Casadei MA. Galli C. Mandolini L. J. Am. Chem. Soc.  1984,  106:  1051 
• 7d Mori K. Fukamatsu K. Liebigs Ann. Chem.  1992,  489 
• 7e Ihara M. Ohnishi M. Takano M. Makita K. Taniguchi N. Fukumoto K. J. Am. Chem. Soc.  1992,  114:  4408 
• 7f Kim D. Kwak YS. Shin KJ. Tetrahedron Lett.  1994,  35:  9211 
• 7g Tanino K. Aoyagi K. Kirihara Y. Ito Y. Miyashita M. Tetrahedron Lett.  2005,  46:  1169 
• 8 Roskamp EJ. Johnson CR. J. Am. Chem. Soc.  1986,  108:  6062 
• 9a Ito H. Motoki Y. Taguchi T. Hanzawa Y. J. Am. Chem. Soc.  1993,  115:  8835 
• 9b Hanzawa Y. Ito H. Taguchi T. Synlett  1995,  299 
• 9c Paquette LA. Cunière N. Org. Lett.  2002,  4:  1927 
• 9d Paquette LA. J. Organo­met. Chem.  2006,  691:  2083 
• 9e Aurrecoechea JM. López B. Arrate M. J. Org. Chem.  2000,  65:  6493 
• 10a Menicagli R. Malanga C. Lardicci L. Tinucci L. Tetrahedron Lett.  1980,  21:  4525 
• 10b Menicagli R. Malanga C. Lardicci L. J. Org. Chem.  1982,  47:  2288 
• 10c Meek SJ. Pradaux F. Demont EH. Harrity JPA. Org. Lett.  2006,  8:  5597 
• 11 For review of contraction of carbohydrate, see: Redlich H. Angew. Chem., Int. Ed. Engl.  1994,  33:  1345 
• 12 Stork G. Cohen JF. J. Am. Chem. Soc.  1974,  96:  5270 
• 13a Lallemand JY. Onanga M. Tetrahedron Lett.  1975,  16:  585 
• 13b Petschen I. Parrilla A. Bosch MP. Amela C. Botar AA. Camps F. Guerrero A. Chem. Eur. J.  1999,  5:  3299 
• 14 Krohn K. Börner G. J. Org. Chem.  1994,  59:  6063 
• 16a Isobe M. Kitamura M. Goto T. J. Am. Chem. Soc.  1982,  104:  4997 
• 16b Kitamura M. Isobe M. Ichikawa Y. Goto T. J. Am. Chem. Soc.  1984,  106:  3252 
• 16c Isobe M. Ichikawa Y. Bai D.-L. Masaki H. Goto T. Tetrahedron  1987,  43:  4767 
• 16d Ichikawa Y. Tsuboi K. Jiang Y. Naganawa A. Isobe M. Tetrahedron Lett.  1995,  36:  7101 
• 16e Tsuboi K. Ichikawa Y. Jiang Y. Naganawa A. Isobe M. Tetrahedron  1997,  53:  5123 
• For reviews on the heteroconjugate addition, see:
• 17a Isobe M. Nippon Nogeikagaku Kaishi  1981,  55:  47 
• 17b Isobe M. J. Synth. Org. Chem. Jpn.  1983,  41:  51 
• 17c Isobe M. In Perspective in the Organic Chemistry of Sulfur   Zwanenburg B. Klunder AJH. Elsevier Science Publishers B. V.; Amsterdam: 1986.  p.209-229  
• 17d Isobe M. J. Synth. Org. Chem. Jpn.  1994,  52:  968 
• 17e Isobe M. Kira K. J. Synth. Org. Chem. Jpn.  2000,  58:  99 
• 18 Tsuboi K. Ichikawa Y. Isobe M. Synlett  1997,  713 
• 19 Isobe M. Kitamura M. Goto T. Tetrahedron Lett.  1979,  20:  3465 
• 23 Marshall JA. Trometer JD. Cleary DG. Tetrahedron  1989,  45:  391 
• 24 Kolb HC. Sharpless KB. Tetrahedron  1992,  48:  10515 
• For hydrosilylation with a catalytic amount of Co complex, see:
• 25a Isobe M. Nishizawa R. Nishikawa T. Yoza K. Tetrahedron Lett.  1999,  40:  6972 
• 25b Liu T.-Z. Kirschbaum B. Isobe M. Synlett  2000,  587 
• 25c Liu T.-Z. Isobe M. Tetrahedron  2000,  56:  5391 
• 25d Baba T. Isobe M. Synlett  2003,  547 
• 25e Baba T. Huang G. Isobe M. Tetrahedron  2003,  59:  6851 
• 26 Isobe M. Kitamura M. Mio S. Goto T. Tetrahedron Lett.  1982,  23:  221 

15

Direct generation of a carbanion by proton abstraction from α-sulfonyl group cannot be achieved due to the fact that an epoxidic proton would be abstracted to convert the epoxide into an enolate under these conditions.

20

The cyclobutane ring structure of 9 was confirmed by X-ray crystallographic analysis (see Supporting Information), and other structures were confirmed through NMR spectroscopy.

21

General Procudure for the Synthesis of Cyclobutane by Heteroconjugate Addition Trimethylsilylacetylene (5 equiv) was dissolved in THF and cooled to -78 ˚C under argon atmosphere. To this cold solution was added a solution of methyllithium-lithium bromide complex (4 equiv) dropwise with stirring. This stirring was continued at -78 ˚C for 30 min, and then a solution of vinylsulfone-epoxide (1 equiv) in THF was added to this mixture. After stirring for further 20 min, the reaction mixture was allowed to warm to -44 ˚C, and the temperature was kept at -44 ˚C for 40 min, then at -23 ˚C for 1 h. The reaction mixture was poured into an ice-cooled sat. aq NH₄Cl. The aqueous layer was separated and extracted with Et₂O. The extracts were combined, washed with H₂O and brine, and then dried over Na₂SO₄. The solution was concentrated in vacuo, and the residue was purified by flash column chromatography to give the corresponding cyclobutane.

22

Cyclobutane 9: IR (KBr): ν_max = 3448, 2957, 2858, 1448, 1284, 1252, 1134, 1117, 842 cm^-¹. ^¹H NMR (600 MHz, CDCl₃): δ = -0.14 (3 H, s), 0.08 (6 H, s), 0.17 (9 H, s), 0.47 (3 H, s), 0.94 (9 H, s), 3.41 (1 H, br d, J = 8.6 Hz), 3.51 (1 H, dt, J = 11.5, 8.4 Hz), 3.63 (1 H, t, J = 9.5 Hz), 3.79 (1 H, dd, J = 9.7, 5.4 Hz), 4.27 (1 H, d, J = 8.1 Hz), 4.87 (1 H, br dt, J = 9.3, 4.8 Hz), 4.94 (1 H, d, J = 11.5 Hz), 4.98 (1 H, d, J = 4.1 Hz), 7.26 (2 H, t, J = 7.5 Hz), 7.36 (1 H, t, J = 7.5 Hz), 7.49 (2 H, t, J = 7.5 Hz), 7.61-7.68 (3 H, m), 7.91 (2 H, d, J = 7.5 Hz). ^¹³C NMR (150 MHz, CDCl₃): δ = -5.4, -5.4, -3.6, -2.6, -0.3, 18.3, 25.9, 45.8, 47.6, 57.4, 65.0, 70.9, 71.5, 91.6, 104.0, 127.8, 128.8, 129.0, 130.1, 134.0, 134.6, 135.8, 140.5. Anal. Calcd for C₃₁H₄₈O₅SSi₃: C, 60.34; H, 7.84. Found: C, 60.34; H, 7.98.
Cyclobutane 10: IR (KBr): ν_max = 3493, 2956, 2172, 1428, 1247, 1147, 1023, 967, 848 cm^-¹. ^¹H NMR (400 MHz, C₆D₆, 318 K): δ = 0.09 (6 H, s), 0.10 (9 H, s), 0.54 (3 H, s), 0.56 (3 H, s), 1.00 (9 H, s), 2.09 (1 H, d, J = 5.4 Hz), 3.08 (1 H, ddd, J = 9.4, 7.4, 2.3 Hz), 3.30 (1 H, dd, J = 9.1, 7.2 Hz), 3.37 (1 H, t, J = 9.1 Hz), 3.46 (1 H, dd, J = 10.5, 5.0 Hz), 3.56 (1 H, dd, J = 10.5, 5.0 Hz), 4.10 (1 H, td, J = 5.0, 2.3 Hz), 4.37 (1 H, td, J = 7.2, 5.5 Hz), 7.06-7.20 (3 H, m), 7.30-7.40 (3 H, m), 7.71-7.76 (2 H, m), 7.87-7.92 (2 H, m). ^¹³C NMR (100 MHz, C₆D₆): δ = -5.4, -5.4, -1.7, -0.7, -0.1, 18.6, 26.1, 37.2, 48.2, 56.1, 66.5, 68.4, 71.6, 87.7, 103.8, 128.7, 128.8, 129.1, 129.9, 133.3, 133.9, 138.4, 139.6. Anal. Calcd for C₃₁H₄₈O₅SSi₃: C, 60.34; H, 7.84. Found: C, 60.34; H, 7.96.

27

Cyclobutane 20: [α]_D ^²7 -14.5 (c 1.15, CHCl₃). IR (KBr): ν_max = 3525, 3031, 2172, 1305, 1148 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = -0.02 (9 H, s), 0.40 (3 H, s), 0.41 (3 H, s), 2.61 (1 H, m), 2.91 (1 H, td, J = 9.0, 3.0 Hz), 2.95 (1 H, t, J = 9.0 Hz), 3.38 (2 H, d, J = 6.0 Hz), 3.48 (1 H, t, J = 9.0 Hz), 3.57 (1 H, dd, J = 11.5, 6.5 Hz), 3.64 (1 H, dd, J = 11.5, 6.5 Hz), 3.98 (1 H, td, J = 6.0, 3.0 Hz), 4.38 (1 H, d, J = 11.5 Hz), 4.44 (1 H, d, J = 11.5 Hz), 7.25-7.76 (15 H, m). ^¹³C NMR (100 MHz, CDCl₃): δ = -1.4, -1.1, -0.1, 27.1, 39.6, 40.8, 60.5, 64.1, 70.5, 71.9, 73.4, 87.2, 104.0, 127.9, 127.9, 127.9, 128.4, 128.4, 129.1, 129.7, 133.5, 133.6, 137.4, 137.7, 138.3. Anal. Calcd for C₃₃H₄₂O₅SSi₂: C, 65.32; H, 6.98. Found: C, 65.32; H, 7.04.

28

Cyclobutane 24: [α]_D ^²² -34.2 (c 0.56, CHCl₃). IR (KBr):
ν_max = 3358, 3066, 3030, 1287, 1136 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 0.03 (9 H, s), 0.55-0.66 (2 H, m), 0.72-0.84 (4 H, m), 0.89 (9 H, t, J = 7.5 Hz), 2.77 (1 H, tdd, J = 10.5, 7.5, 2.5 Hz), 3.26 (1 H, ddd, J = 10.5, 6.0, 1.0 Hz), 3.69 (1 H, dd, J = 12.5, 2.5 Hz), 3.73 (1 H, dd, J = 10.0, 5.0 Hz), 3.83 (1 H, dd, J = 10.0, 5.0 Hz), 3.86 (1 H, dd, J = 12.5, 7.5 Hz), 4.20 (1 H, dd, J = 10.5, 1.0 Hz), 4.56 (1 H, d, J = 11.5 Hz), 4.61 (1 H, d, J = 11.5 Hz), 4.98 (1 H, td, J = 6.0, 3.0 Hz), 7.28-7.39 (5 H, m), 7.48-7.54 (2 H, m), 7.61-7.67 (1 H, m), 7.92-7.96 (2 H, m). ^¹³C NMR (100 MHz, CDCl₃): δ = -0.4, 3.7, 8.2, 32.5, 43.2, 46.6, 60.7, 63.1, 67.6, 72.5, 73.2, 90.2, 104.8, 127.8, 127.9, 128.4, 128.9, 129.1, 133.8, 137.8, 140.9. Anal. Calcd for C₃₁H₄₆O₅SSi₂: C, 63.44; H, 7.90. Found: C, 63.44; H, 7.97.