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Synlett 2008(20): 3203-3207  
DOI: 10.1055/s-0028-1087366
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Hydroxyalkyl Thiazolines, a New Class of Highly Efficient Ligands for Carbonyl Additions

Michael Bauer, Frauke Maurer, Svenja M. Hoffmann, Uli Kazmaier*
Institut für Organische Chemie, Universitaet des Saarlandes, 66123 Saarbruecken, Germany
Fax: +49(681)3022409; e-Mail: u.kazmaier@mx.uni-saarland.de;
Further Information

Publication History

Received 27 August 2008
Publication Date:
24 November 2008 (online)

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Abstract

Hydroxyalkyl thiazoline ligands can easily be obtained in an isonitrile-based multicomponent reaction. These ligands are significantly more stable than the comparable oxazoline ligands, and give excellent enantiomeric excess in carbonyl additions of alkyl- and arylzinc compounds.

Key words

carbonyl additions - ligands - multicomponent reactions - nonlinear effect - thiazolines

    References and Notes

  • 1 McManus HA. Guiry PJ. Chem. Rev.  2004,  104:  4151 ; and references cited therein
    CrossrefGoogle Scholar
  • 2a Botteghi C. Schionato A. Chelucci G. Brunner H. Kürzinger A. Obermann U. J. Organomet. Chem.  1989,  370:  17 
    Google Scholar
  • 2b Menges F. Neuburger M. Pfaltz A. Org. Lett.  2002,  4:  4713 
    Google Scholar
  • 2c Boland NA. Casey M. Hynes SJ. Matthews JW. Smyth MP. J. Org. Chem.  2002,  67:  3919 
    Google Scholar
  • 2d Busacca CA. Grossbach D. So RC. O’Brien EM. Spinelli EM. Org. Lett.  2003,  5:  595 
    Google Scholar
  • 2e Bastero A. Claver C. Ruiz A. Castillón S. Daura E. Bo C. Zangrando E. Chem. Eur. J.  2004,  10:  3747 
    Google Scholar
  • 2f Bhor S. Anilkumar G. Tse MK. Klawonn M. Döbler C. Bitterlich B. Grotevendt A. Beller M. Org. Lett.  2005,  7:  3393 
    Google Scholar
  • 2g Weiss ME. Fischer DF. Xin Z. Jautze S. Schweizer WB. Peters R. Angew. Chem. Int. Ed.  2006,  45:  5694; Angew. Chem. 2006, 118: 5823 
    Google Scholar
  • 2h Ma K. You J. Chem. Eur. J.  2007,  13:  1863 
    Google Scholar
  • 2i Arai T. Mizukami T. Yanagisawa A. Org. Lett.  2007,  9:  1145 
    Google Scholar
  • 3 Molina P. Tárraga A. Curiel D. Synlett  2002,  435 
    Article in Thieme ConnectGoogle Scholar
  • 4 Helmchen G. Krotz A. Ganz K.-T. Hansen D. Synlett  1991,  257 
    Article in Thieme ConnectGoogle Scholar
  • 5a Le MauxP. Abrunhosa I. Berchel M. Simonneaux G. Gulea M. Masson S. Tetrahedron: Asymmetry  2004,  15:  2569 
    Google Scholar
  • 5b Abrunhosa I. Delain-Bioton L. Gaumont A.-C. Gulea M. Masson S. Tetrahedron  2004,  60:  9263 
    Google Scholar
  • 6a Lu S.-F. Du D.-M. Zhang S.-W. Xu J. Tetrahedron: Asymmetry  2004,  15:  3433 
    Google Scholar
  • 6b Du D.-M. Lu S.-F. Fang T. Xu J. J. Org. Chem.  2005,  70:  3712 
    Google Scholar
  • 7a Nishio T. Kodama Y. Tsurumi Y. Phosphorus, Sulfur Silicon Relat. Elem.  2005,  180:  1449 
    Google Scholar
  • 7b Yamakuchi M. Matsunaga H. Tokuda R. Ishizuka T. Nakajima M. Kunieda T. Tetrahedron Lett.  2005,  46:  4019 
    Google Scholar
  • 8 Casey M. Smyth MP. Synlett  2003,  102 
    Google Scholar
  • 9 Kazmaier U. Bauer M. J. Organomet. Chem.  2006,  691:  2155 
    CrossrefGoogle Scholar
  • 10 Yamakuchi M. Matsunaga H. Tokuda R. Ishizuka T. Nakajima M. Kunieda T. Tetrahedron Lett.  2005,  46:  4019 
    CrossrefGoogle Scholar
  • 11 Fu B. Du D.-M. Xia Q. Synthesis  2004,  221 
    Article in Thieme ConnectGoogle Scholar
  • 12 Nishio T. J. Org. Chem.  1997,  62:  1106 
    CrossrefGoogle Scholar
  • 13 Abrunhosa I. Gulea M. Levillain J. Masson S. Tetrahedron: Asymmetry  2001,  12:  2851 
    CrossrefGoogle Scholar
  • 14 Lafrague P. Guenot P. Lellouche J.-P. Synlett  1995,  171 
    Article in Thieme ConnectGoogle Scholar
  • 15a Ugi I. Meyr R. Fetzer U. Steinbrückner C. Angew. Chem.  1959,  71:  386 
    Google Scholar
  • 15b Ugi I. Steinbrückner C. Angew. Chem.  1960,  72:  267 
    Google Scholar
  • 18 General Procedure for ZnEt 2 Additions towards Aldehydes A solution of ZnEt2 in hexane (15%, 2 mL, 1.76 mmol) was added to the ligand (S,S)-2 (4.3 mg, 0.02 mmol, 2 mol%) in toluene (2 mL) in a Schlenk tube under argon. The mixture was stirred at r.t. for 30 min before the aldehyde (1 mmol) in toluene (1 mL) was added. After 22 h, 1 N HCl was added. After stirring for 10 min the product was extracted with Et2O (twice) and the enantiomeric ratio of the crude product was determined by GC using a chiral cyclodextrin column. Afterwards the crude product was purified by flash chromatography
  • 19a Noyori R. Kitamura M. Angew. Chem., Int. Ed. Engl.  1991,  30:  49 ; Angew. Chem. 1991, 103, 34
    Google Scholar
  • 19b Soai K. Niwa S. Chem. Rev.  1992,  92:  833 
    Google Scholar
  • 19c Pu L. Yu H.-B. Chem. Rev.  2001,  101:  757 
    Google Scholar
  • 19d Yamakawa M. Noyori R. J. Am. Chem. Soc.  1995,  117:  6327 
    Google Scholar
  • 20a Soai K. Kawase Y. J. Chem. Soc., Perkin Trans. 1  1990,  3214 
    Google Scholar
  • 20b Soai K. Kawase Y. Oshio A. J. Chem. Soc., Perkin Trans. 1  1991,  1613 
    Google Scholar
  • 21 Dosa PI. Ruble JC. Fu GC. J. Org. Chem.  1997,  62:  444 
    CrossrefPubMedGoogle Scholar
  • 22a Huang W.-S. Pu L. J. Org. Chem.  1999,  64:  4222 
    Google Scholar
  • 22b Huang W.-S. Hu Q.-S. Pu L. J. Org. Chem.  1999,  64:  7940 
    Google Scholar
  • 22c Huang W.-S. Pu L. Tetrahedron Lett.  2000,  41:  145 
    Google Scholar
  • 22d Qin Y.-C. Pu L. Angew. Chem. Int. Ed.  2006,  45:  273 ; Angew. Chem. 2006, 118, 279
    Google Scholar
  • 23a Ko D.-H. Kim KH. Ha D.-C. Org. Lett.  2002,  4:  3759 
    Google Scholar
  • 23b Fontes M. Verdaguer X. Solà L. Pericàs MA. Riera A. Org. Chem.  2004,  69:  2532 
    Google Scholar
  • 23c Wu X. Liu X. Zhao G. Tetrahedron: Asymmetry  2005,  16:  2299 
    Google Scholar
  • 23d Kim PG. Walsh PJ. Angew. Chem. Int. Ed.  2006,  45:  4175; Angew. Chem. 2006, 118, 4281 
    Google Scholar
  • 23e Wang M.-C. Zhang Q.-J. Zhao W.-X. Wang X.-D. Ding X. Jing T.-T. Song M.-P. J. Org. Chem.  2008,  73:  168 
    Google Scholar
  • 24a Wu P.-Y. Wu H.-L. Uang B.-J. J. Org. Chem.  2006,  71:  833 
    Google Scholar
  • 24b Jin M.-J. Sarkar SM. Lee DH. Qiu H. Org. Lett.  2008,  10:  1235 
    Google Scholar
  • 25a Bolm C. Muñiz K. Chem. Commun.  1999,  1295 
    Google Scholar
  • 25b Bolm C. Hermanns N. Hildebrand JP. Muñiz K. Angew. Chem. Int. Ed.  2000,  39:  3465 ; Angew. Chem. 2000, 112, 3607
    Google Scholar
  • 25c Bolm C. Kesselgruber M. Hermanns N. Hildebrand JP. Raabe G. Angew. Chem. Int. Ed.  2001,  40:  1488 ; Angew. Chem. 2001, 113, 1536
    Google Scholar
  • 25d Bolm C. Zani L. Rudolph J. Schiffers I. Synlett  2004,  2173 
    Google Scholar
  • 25e Bolm C. Schmidt F. Zani L. Tetrahedron: Asymmetry  2005,  16:  1367 
    Google Scholar
  • 26a Rudolph J. Schmidt F. Bolm C. Adv. Synth. Catal.  2004,  346:  867 
    Google Scholar
  • 26b Dahmen S. Lormann M. Org. Lett.  2005,  7:  4597 
    Google Scholar
  • 27a Bolm C. Rudolph J. J. Am. Chem. Soc.  2002,  124:  14850 
    Google Scholar
  • 27b Rudolph J. Schmidt F. Bolm C. Synthesis  2005,  840 
    Google Scholar
  • 27c Schmidt F. Rudolph J. Bolm C. Adv. Synth. Catal.  2007,  349:  703 
    Google Scholar
  • 30 Ishiyama T. Takagi J. Ishida K. Miyaura N. Anastasi NR. Hartwig JF. J. Am. Chem. Soc.  2002,  124:  390 
    CrossrefPubMedGoogle Scholar
16

Synthesis of Thioamide 1 Pivalaldehyde (7.82 mL, 72.0 mmol) and (S)-2-isocyano-3-methyl-1-butanol (5.46 g, 48.2 mmol) were added to a solution of Na2S2O3 (11.4 g, 72.0 mmol) and PPTS (18.1 g, 72.0 mmol) in H2O (40 mL) at 0 ˚C. The mixture was allowed to stir at 0 ˚C for further 30 min, before the ice bath was removed and the solution warmed to r.t. Then, H2O was added, and the product was extracted three times with CH2Cl2. The combined organic layers were extracted with aq NaHCO3, KHSO4, and H2O and dried over Na2SO4. After evaporation of the solvent, the crude product was purified by flash chromatography (silica gel, hexanes-EtOAc, 7:3) giving rise to a colorless solid. The diastereomeric thioamides could be separated by crystallization from benzene, providing (R,S)-1 (1.59 g, 6.9 mmol, 36%) as colorless crystals; mp 129-130 ˚C. The S,S-isomer was obtained (1.78 g, 7.7 mmol, 41%) by a second flash chromatography (silica gel, hexanes-EtOAc, 8:2) as a colorless oil, which solidified to a wax. R f  = 0.47 [(S,S)-1] and 0.53 [(R,S)-1] (Et2O).
Compound (R,S)-1: [α]D ²0 -57 (c 1.3, CHCl3). ¹H NMR (500 MHz, DMSO-d 6): δ = 0.89, 0.92 (2 d, J = 6.8 Hz, 6 H), 0.94 (s, 9 H), 2.07 (m, 1 H), 3.49 (ddd, J = 9.9, 4.8, 4.6 Hz, 1 H), 3.58 (ddd, J = 9.9, 5.0, 4.8 Hz, 1 H), 4.03 (d, J = 6.0 Hz,
1 H), 4.35 (dddd, J = 9.0, 7.0, 4.8, 4.6 Hz, 1 H), 4.69 (dd, J = 5.0, 4.8 Hz, 1 H), 5.41 (d, J = 6.0 Hz, 1 H), 9.07 (d, J = 9.0 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 18.8, 19.1, 26.6, 27.8, 34.8, 59.5, 60.9, 84.1, 202.5. HRMS (CI): m/z calcd for C11H24NO2S [M + H]+: 234.1528; found: 234.1530. Anal. Calcd for C11H23NO2S (233.37): C, 56.61; H, 9.93; N, 6.00. Found: C, 56.60; H, 9.70; N, 5.96.
Compound (S,S)-1: [α]D ²0 -92 (c 1.7, CHCl3). ¹H NMR (500 MHz, DMSO-d 6): δ = 0.89, 0.91 (2 d, J = 6.9 Hz, 6 H), 0.95 (s, 9 H), 2.07 (m, 1 H), 3.50 (ddd, J = 11.0, 4.9, 4.7 Hz, 1 H), 3.60 (ddd, J = 11.0, 5.0, 4.8 Hz, 1 H), 4.05 (d, J = 5.9 Hz,
1 H), 4.34 (dddd, J = 8.8, 6.9, 4.8, 4.7 Hz, 1 H), 4.68 (dd, J = 5.0, 4.9 Hz, 1 H), 5.42 (d, J = 5.9 Hz, 1 H), 9.13 (d, J = 8.8 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 19.0, 26.7, 28.0, 34.9, 59.3, 61.0, 84.2, 202.7. HRMS (CI): m/z calcd for C11H24NO2S [M + H]+: 234.1528; found: 234.1547. Anal. Calcd for C11H23NO2S (233.37): C, 56.61; H, 9.93; N, 6.00. Found: C, 56.61; H, 9.70; N, 5.62.

17

Synthesis of the Thiazoline Ligand ( S , S )-2 Thioamide (S,S)-1 (8.40 g, 36.0 mmol) and Et3N (11.1 mL, 79.2 mmol) were dissolved in abs. THF (180 mL). This solution was cooled to 0 ˚C before MsCl (3.09 mL, 39.6 mmol) in THF (35 mL) was added dropwise. After the addition was complete, the ice bath was removed and the mixture allowed to warm to r.t. The mixture was diluted with Et2O and washed with H2O. After drying of the organic layer (Na2SO4) and evaporation of the solvent a colorless solid (7.44 g, 34.4 mmol, 96% yield) was obtained. The crude product was crystallized twice (hexane) giving colorless crystals (3.02 g, 14.0 mmol, 39% yield); mp 88-90 ˚C. R f  = 0.19 (hexane-Et2O, 8:2). [α]D ²0 -57 (c 1.4, CHCl3). ¹H NMR (500 MHz, CDCl3): δ = 0.96 (d, J = 6.8 Hz, 3 H), 0.99 (s, 9 H), 1.03 (d, J = 6.8 Hz, 3 H), 1.97 (m, 1 H), 3.04 (dd, J = 10.5, 10.1 Hz, 1 H), 3.29 (dd, J = 10.5, 8.7 Hz, 1 H), 3.61 (br s, 1 H), 4.05 (d, J = 4.0 Hz, 1 H), 4.17 (dddd, J = 10.1, 8.7, 6.5, 1.1 Hz, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 18.9, 19.6, 25.9, 32.8, 35.2, 35.8, 79.5, 81.6, 172.8. HPLC: column: LiChrosorb Si 60, hexane-Et2O (90:10), flow: 2.0 mL/min; t R = 11.80 min. HRMS (CI): m/z calcd for C11H22NOS [M + H]+: 216.1422. Found: 216.1447. Anal. Calcd for C11H21NOS (215.35): C, 61.35; H, 9.83; N, 6.50. Found: C, 61.17; H, 9.50; N, 6.36.
Synthesis of the Thiazoline Ligand ( R , S )-2 Ligand (R,S)-2 was prepared according to the same procedure from (R,S)-1 (466 mg, 2.00 mmol). The crude product was purified by flash chromatography giving rise to colorless crystals (363 mg, 1.69 mmol, 85% yield); mp 69 ˚C. R f  = 0.38 (hexane-Et2O, 8:2). [α]D ²0 -71 (c 1.5, CHCl3). ¹H NMR (500 MHz, CDCl3): δ = 0.97 (d, J = 6.8 Hz, 3 H), 1.005 (s, 9 H), 1.006 (d, J = 6.8 Hz, 3 H), 1.98 (m, 1 H, 5-H), 3.07 (dd, J = 10.9, 9.1 Hz, 1 H), 3.33 (dd, J = 10.9, 9.0 Hz, 1 H), 3.59 (d, J = 4.5 Hz, 1 H), 3.99 (m,
1 H), 4.23 (dddd, J = 9.1, 9.0, 6.4, 1.7 Hz, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 19.1, 19.4, 26.0, 32.6, 35.4, 35.7, 79.5, 81.5, 171.8. HPLC: column: LiChrosorb Si 60, hexanes-Et2O (90:10), flow: 2.0 mL/min; t R = 5.65 min. HRMS (CI): m/z calcd for C11H22NOS [M + H]+: 216.1422; found: 216.1445. Anal. Calcd for C11H21NOS (215.35): C, 61.35; H, 9.83; N, 6.50. Found: C, 60.93; H, 9.65; N, 6.45.

28

General Procedure for Arylations of Aldehydes
The pinacol ester of phenylboronic acid (306 mg, 1.5 mmol) was dissolved in toluene (4 mL) in a Schlenk tube. A 1 M solution of ZnEt2 in hexane (1.5 mL, 1.5 mmol) was added, and the mixture was heated to 60 ˚C for 12 h. After cooling to r.t., this solution was added to the ligand (S,S)-2 (5.4 mg, 0.025 mmol, 5 mol%) in another Schlenk tube. After stirring for 10 min at r.t., the aldehyde was added in hexane (1 mL). The reaction was monitored by TLC. After complete conversion, sat. NH4Cl solution was added to quench the reaction and the aqueous layer was extracted with CH2Cl2 (2 ×). The combined organic layers were dried and evaporated. The product was purified by flash chromatography, and the enantiomeric ratio was determined by HPLC (Chiracel OD-H).

29

The ee was determined by HPLC using the chiral column Chiracel OD-H.