Synlett 2004(13): 2275-2280  
DOI: 10.1055/s-2004-832835
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereospecific Reaction of α-Carbamoyloxy-2-alkenylboronates and α-Carbamoyloxy-alkylboronates with Grignard Reagents - Synthesis of Highly Enantioenriched Secondary Alcohols

Edith Beckmann, Vidya Desai, Dieter Hoppe*
Westfälische Wilhelms-Universität Münster, Organisch-Chemisches Institut, Corrensstr. 40, 48149 Münster, Germany
Fax: +49(251)8336531; e-Mail: [email protected];
Further Information

Publication History

Received 29 July 2004
Publication Date:
24 September 2004 (online)

Abstract

Highly enantioenriched secondary alcohols were synthesized by treatment of α-carbamoyloxy-2-alkenylboronates and α-carbamoyloxy-alkylboronates with Grignard reagents. An intermediary boronate complex was transformed stereospecifically to the corresponding secondary 2-alkenyl- and alkylboronates by migration of an introduced residue. Oxidative workup furnished the enantioenriched secondary alcohols.

    References

  • 1 Review: Hoffmann RW. Stereoselective Synthesis of Polyketide Natural Products - Achievements and Future Development, In Stereocontrolled Organic Synthesis   Trost BM. Blackwell; Oxford (UK): 1994.  p.259 
  • 2a Sibi MP. Cook GR. Liu P. Tetrahedron Lett.  1999,  40:  2477 
  • 2b Chiodi O. Fotiadu F. Sylvestre M. Buono G. Tetrahedron Lett.  1996,  37:  39 
  • 2c Giffels G. Deisbach C. Kragl U. Weigerding M. Waldmann H. Wandrey C. Angew. Chem., Int. Ed. Engl.  1995,  34:  2005 ; Angew. Chem. 1995, 107, 2165
  • 2d Bolm C. Felder M. Tetrahedron Lett.  1993,  34:  6041 
  • 2e Corey EJ. Bakshi RK. Shibata S. Chen CP. Singh VK. J. Am. Chem. Soc.  1987,  109:  7925 
  • 2f Suda H. Motoi M. Fuji M. Kanoh S. Yoshida H. Tetrahedron Lett.  1979,  19:  4565 
  • 2g Locatelli M. Cozzi PG. Angew. Chem. Int. Ed.  2003,  42:  4928 ; Angew. Chem. 2003, 115, 5078
  • 2h Review: Noyori R. Kitamura M. Ohkuma T. Proc. Natl. Acad. Sci.  2004,  101:  5356 
  • 3a Denmark SE. Fu J. Chem. Rev.  2003,  103:  2763 
  • 3b Bandini M. Cozzi PG. Umani-Ronchi A. Tetrahedron  2001,  57:  835 
  • 3c Weber B. Seebach D. Tetrahedron  1994,  50:  7473 
  • 3d Noyori R. Suga S. Kawai K. Okada S. Kitamura M. Pure Appl. Chem.  1988,  60:  1597 
  • 3e Corey EJ. Hannon FJ. Tetrahedron Lett.  1987,  28:  5233 
  • 5a Hoppe D. Hintze F. Tebben P. Angew. Chem., Int. Ed. Engl.  1990,  29:  1422 ; Angew. Chem. 1990, 102, 1457
  • 5b Beak P. Zajdel WJ. J. Am. Chem. Soc.  1984,  106:  1010 
  • 5c For reviews see: Hoppe D. Hense T. Angew. Chem., Int. Ed. Engl.  1997,  36:  2282 ; Angew. Chem. 1997, 109, 2376
  • 5d Marr F. Brüggemann M. Hoppe D. Enantioselective Synthesis by Lithiation Adjacent to Oxygen and Electrophile Incorporation, In Topics in Organometallic Chemistry   Vol. 5:  Hodgson DM. Springer; Berlin: 2003.  p.61 
  • 7 Matteson DS. Stereodirected Synthesis with Organoboranes   Springer; Berlin: 1995. 
  • 8a Matteson DS. Majumdar D. Organometallics  1983,  2:  230 
  • 8b Tsai DJS. Matteson DS. Organometallics  1983,  2:  236 
  • 9a Matteson DS. Mah RWH. J. Am. Chem. Soc.  1963,  85:  2599 
  • 9b Matteson DS. Mah RWH. J. Org. Chem.  1963,  28:  2171 
  • 10a Matteson DS. Sadhu KM. Peterson ML. J. Am. Chem. Soc.  1986,  108:  810 
  • 10b Tripathy PB. Matteson DS. Synthesis  1990,  200 
  • 13a Hoffmann RW. Hölzer B. Knopff O. Org. Lett.  2001,  12:  1945 
  • 13b Hoffmann RW. Hölzer B. Knopff O. Harms K. Angew. Chem. Int. Ed.  2000,  39:  3072 ; Angew. Chem. 2000, 112, 3206
  • 14 Belelie JL. Chong JM. J. Org. Chem.  2001,  66:  5552 
  • 16 Andersen MW. Hildebrandt B. Köster G. Hoffmann RW. Chem. Ber.  1989,  122:  1777 
  • 18 Papillon JPN. Taylor RJK. Org. Lett.  2002,  4:  119 
  • 19a Ebner T. Eichelbaum M. Fischer P. Meese CO. Arch. Pharm.  1989,  322:  399 
  • 19b Clemo GR. Raper R. Short WS. J. Chem. Soc.  1949,  663 
  • 20a Harrison JR. O’Brien P. Porter DW. Smith NM. Chem. Commun.  2001,  1202 
  • 20b Dearden MJ. Firkin CR. Hermet J.-PR. O’Brien P. J. Am. Chem. Soc.  2002,  124:  11870 
  • 21 Al-Hassan MI. Miller RB. Synth. Commun.  2001,  31:  3641 
  • 22 Yanagisawa A. Namura N. Naritake Y. Yamamoto H. Synthesis  1991,  12:  1130 
  • 23 Hoffmann RW. Herold T. Chem. Ber.  1981,  114:  375 
  • 24 Ujikawa O. Inanaga J. Yamaguchi H. Tetrahedron Lett.  1989,  30:  2837 
  • 25 Soai K. Hayasa T. Takai K. Sugiyana T. J. Org. Chem.  1994,  59:  7908 
  • 26 Borden WT. J. Am. Chem. Soc.  1970,  92:  4898 
4

Beckmann, E.; Hoppe, D. Synthesis, submitted.

6

Experimental Procedure: The amount of 1.315 g (5.0 mmol, 1.0 equiv) of 3 and 1.490 g (6.0 mmol, 1.2 equiv) of (-)-sparteine were dissolved in 10 mL of anhyd Et2O and the mixture was cooled to -78 °C. To this mixture 5.0 mL (6.0 mmol, 1.2 equiv) of a 1.2 M solution of sec-butyllithium in cyclohexane were added slowly within 15 min with a syringe pump. After a deprotonation time of 5 h 1.410 g (7.5 mmol, 1.5 equiv) triisopropyl borate were added at -78 °C and the reaction mixture was stirred for an additional hour. The reaction was quenched with 5 mL of 2 M HCl at -78 °C and the layers were separated. The aqueous layer was extracted with Et2O (3 × 5 mL), the combined organic extracts were dried with MgSO4 and the solvent was removed in vacuum. The crude product was dissolved in 10 mL of CH2Cl2 and added to a flask charged with 885 mg (7.5 mmol, 1.5 equiv) of pinacol, 0.050 g of p-toluenesulfonic acid and MgSO4. This mixture was stirred at r.t. for 24 h, the solid material was filtered off and the solvent was removed. After purification of the crude product by flash column chromatography (SiO2, cyclohexane-EtOAc = 5:1) we obtained 1.788 g (4.5 mmol, 90%) of compound 5 as a colorless oil. The ee was determined by 1H NMR shift experiment using 30 mol% of Eu(hfc)3. Rf = 0.24 (Et2O-pentane = 1:1); [α]D 20 +36.7 (c 0.97, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 1.27 [s, 12 H, CH3 (pinacol)], 1.29-1.35 [m, 12 H, CH3 (Cb)], 1.94-2.19 (m, 2 H, CH2), 2.75-2.98 (m, 2 H, CH2), 3.85, 4.14 [sep, 2 H, CH(Cb), 3 J = 7.0 Hz)], 3.92 (dd, 1 H, CH, 3 J = 4.2 Hz, 3 J = 10.3 Hz), 7.21-7.38 [m, 5 H, CH(Ar)] ppm. 13C NMR (75 MHz, CDCl3): δ = 20.2, 20.3, 20.6 [CH3 (pinacol) + CH3(Cb)], 26.9 (CH2), 33.3 (CH2), 46.7, 48.4 [CH(Cb)], 79.8 (CH), 125.6 [Cq(pinacol)], 128.2, 128.5 [CH(Ar)], 142.5 [Cq(Ar)], 162.7 [C=O(Cb)] ppm. Anal. Calcd for C22H36BNO4 (389.27): C, 67.87; H, 9.32; N, 3.60. Found: C, 67.76; H, 9.36; N, 3.85.

11

Experimental Procedure: The amount of 163 mg (0.5 mmol, 1.0 equiv) of 2 was dissolved in 5 mL of anhyd Et2O and cooled to -78 °C. To this mixture 1.0 mmol (2.0 equiv) of the Grignard reagent as solution in Et2O was slowly added. The mixture was stirred for 1 h at -78 °C and then warmed to r.t. for an additional hour. The solution was quickly filtered over ca. 5 g of silica gel with pentane and the solvent was removed carefully at 800 mbar to furnish the crude product 14, which was subjected to the subsequent reactions without further purification.

12

The crude product 14 was dissolved in 5.00 mL of THF. At r.t., 1.20 mL (0.6 mmol, 1.2 equiv) of 0.5 M NaOH was added dropwise and after 5 min, 0.07 mL (0.7 mmol, 1.4 equiv) H2O2 (35%) was added. The mixture was stirred for 30 min at r.t., then diluted with 5.00 mL of H2O and the layers were separated. The aqueous layer was extracted with Et2O (3 × 5 mL), the combined organic extracts were washed with sat. FeSO4 solution to destroy the peroxides and then dried with MgSO4. After removal of the solvent in vacuum the crude product was purified by flash column chromatography (SiO2, Et2O-pentane = 1:6) to furnish the alcohols 15 as colorless liquids. Compound 15a: [21] Rf = 0.44 (Et2O-pentane = 1:1); [α]D 20 -8.3 (c 0.85, CHCl3). The ee was determined by 1H NMR shift experiment with 40 mol% of Eu(hfc)3. Compound 15b: [22] Rf = 0.46 (Et2O-pentane = 1:1); [α]D 20 -7.4 (c 0.76, CHCl3). The ee was determined by chiral HPLC (column: chiragrom 2, 60 × 2 mm; solvent: i-PrOH-hexane = 1:600). Compound 15c: Rf = 0.52 (Et2O-pentane = 1:1); [α]D 20 -11.8 (c 2.4, EtOH). The ee was determined by comparison of optical rotation. [14] Compound 15d: Rf = 0.59 (Et2O-pentane = 1:1); [α]D 20 -3.3 (c 1.1, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 1.19-1.71 [m, 19 H, CH2 (oct), CH(oct), CH3, OH], 3.81 [t, 1 H, CH(OH), 3 J = 6.2 Hz], 5.46 (ddq, 1 H, CH, 4 J = 1.0 Hz, 3 J = 7.0 Hz, 3 J = 15.2 Hz), 5.63 (ddq, 1 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 19.5 (CH3), 25.7, 29.6, 30.0, 37.8 [CH2 (oct)], 42.3 [CH(oct)], 75.2 [CH(OH)], 127.0, 133.8 (CH=CH) ppm. Anal. Calcd for C12H22O (182.17): C, 79.06; H, 12.16. Found: C, 78.67; H, 12.44. The ee was determined by 1H NMR shift experiment with 40 mol% of Eu(hfc)3.

15

The crude product 14 was dissolved in 5 mL of anhyd toluene and 106 mg (1.0 mmol, 2.0 equiv) of benzaldehyde were added. The mixture was heated to 60 °C for 12 h and then cooled to r.t. The toluene was removed in vacuo, the residue was dissolved in 5 mL of Et2O, and 90 mg (0.6 mmol, 1.2 equiv) of triethanolamine were added. After one hour of stirring at r.t. the precipitate was filtered off and the solvent was removed. Flash column chromatography of the crude product (SiO2, Et2O-pentane = 1:5) furnished the homoallyl alcohols 17 as colorless liquids. The E:Z-ratios of the compounds were determined by 1H NMR of the crude products. The ee were determined by HPLC using a chiral column (chiragrom 2, 250 × 2 mm) and the solvent mixture i-PrOH-hexane = 1:400. Compound 17a: E:Z = 80:20; Rf = 0.54 (Et2O-pentane = 1:1); [α]D 20 +24.3 (c 0.67, CHCl3). Compound 17b: E:Z = 25:75; Rf = 0.57 (Et2O-pentane = 1:1); [α]D 20 +4.7 (c 0.50, CHCl3). Compound 17c: E:Z = 33:67; Rf = 0.69 (Et2O-pentane = 1:1); [α]D 20 +26.5 (c 1.12, CHCl3). Compound 17d: E:Z = 89:11; Rf = 0.58 (Et2O-pentane = 1:1); [α]D 20 +30.1 (c 1.00, CHCl3). Compound 17e: E:Z = 28:72; Rf = 0.69 (Et2O-pentane = 1:1); [α]D 20 +74.2 (c 1.21, CHCl3). Compound (E)-17e: 1H NMR (300 MHz, CDCl3): δ = 0.83 (d, 3 H, CH3, 3 J = 6.9 Hz), 1.01 (s, 9 H, CH3), 2.17 (d, 1 H, OH, 3 J = 2.4 Hz), 3.36-3.49 [m, 1 H, CH(CH3)], 4.27 [dd, 1 H, CH(OH), 3 J = 2.4 Hz, 3 J = 7.9 Hz], 5.25 (dd, 1 H, CH, 3 J = 8.6 Hz, 3 J = 15.9 Hz), 5.63 (d, 1 H, CH, 3 J = 15.9 Hz), 7.23-7.35 [m, 5H, CH(Ar)] ppm. Compound (Z)-17e: 1H NMR (300 MHz, CDCl3): δ = 0.77 (d, 3 H, CH3, 3 J = 6.8 Hz), 1.14 (s, 9 H, CH3), 2.14 (d, 1 H, OH, 3 J = 1.7 Hz), 2.97-3.10 [m, 1 H, CH(CH3)], 4.23 [dd, 1 H, CH(OH), 3 J = 1.7 Hz, 3 J = 8.4 Hz], 5.09 (dd, 1 H, CH, 3 J = 11.0 Hz, 3 J = 11.9 Hz), 5.59 (d, 1 H, CH, 3 J = 11.9 Hz), 7.23-7.35 [m, 5 H, CH(Ar)] ppm. 13C NMR (75 MHz, CDCl3): δ = 17.6 [CH(CH3)], 29.8, 31.6, 33.5 (CH3), 41.2 [CH(CH3)], 79.0 [CH(OH)], 127.0, 127.1, 127.7, 128.2, 130.5 [CH(Ar), CH], 142.4 (CH), 143.1 [Cq(Ar)] ppm. Anal. Calcd for C15H22O (218.17): C, 82.52; H, 10.16. Found: C, 82.17; H, 10.22.

17

Experimental Procedure: The amount of 195 mg (0.5 mmol, 1.0 equiv) of 5 was dissolved in 5.00 mL of anhyd Et2O and the solution was cooled to -78 °C. To this mixture 1.0 mmol (2.0 equiv) of the Grignard reagent as solution in Et2O was slowly added. The mixture was stirred for 1 h at -78 °C and then warmed to r.t. for an additional hour. The solution was quickly filtered over ca. 5 g of silica gel with pentane and the solvent was removed carefully at 800 mbar. The residue was dissolved in 5.00 mL of THF. At r.t. 1.20 mL (0.6 mmol, 1.2 equiv) of 0.5 M NaOH were added dropwise and after 5 min 0.07 mL (0.7 mmol, 1.4 equiv) H2O2 (35%) were added. The mixture was stirred for 30 min at r.t., then diluted with 5.00 mL of H2O and the layers were separated. The aqueous layer was extracted with Et2O (3 × 5 mL), the combined organic extracts were washed with sat. FeSO4 solution to destroy the peroxides and then dried with MgSO4. After removal of the solvent in vacuum the crude product was purified by flash column chromatography (SiO2, Et2O-pentane = 1:6) to furnish the alcohols 20. The ee were determined by HPLC using a chiral column (chiragrom 2, 250 × 2 mm) and the solvent mixture i-PrOH-hexane = 1:400. Compound 20a: [23] colorless liquid; Rf = 0.43 (Et2O-pentane = 1:1); [α]D 20 +11.9 (c 1.00, CHCl3). Compound 20b: [24] white solid; mp 96 °C; Rf = 0.53 (Et2O-pentane = 1:1); [α]D 20 +28.7 (c 0.91, CHCl3). Compound 20c: colorless liquid; Rf = 0.55 (Et2O-pentane = 1:1); [α]D 20 +15.8 (c 0.92, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 1.29-1.82 [m, 16 H, CH2 (oct), CH(oct), OH], 2.67 (ddd, 2 H, CH2, 3 J = 7.0 Hz, 3 J = 9.4 Hz, 3 J = 13.5 Hz), 2.86 (ddd, 2 H, CH2, 3 J = 5.7 Hz, 3 J = 9.4 Hz, 3 J = 13.5 Hz), 3.48 [m, 1 H, CH(OH)], 7.17-7.34 [m, 5 H, CH(Ar)] ppm. 13C NMR (75 MHz, CDCl3): δ = 27.1, 27.5, 26.0, 30.0, 32.7 [CH2(oct), CH2], 36.47 (CH2), 48.1 [CH(oct)], 75.0 [CH(OH)], 127.9, 128.4, 130.0 [CH(Ar)], 141.1 [Cq(Ar)] ppm. Anal. Calcd for C17H26O (246.20): C, 82.87; H, 10.64. Found: C, 82.51; H, 10.86. Compound 20d: [25] colorless liquid; Rf = 0.54 (Et2O-pentane = 1:1); [α]D 20 +27.5 (c 0.85, CHCl3). Compound 20e: [26] colorless liquid; Rf = 0.55 (Et2O-pentane = 1:1); [α]D 20 +50.0 (c 1.15, CHCl3).