Nonenzymatic Kinetic Resolution of 3-Hydroxyalkanamides with Chiral Copper Catalyst

Abstract

Kinetic resolution of 3-hydroxyalkanamides with good to high selectivities was achieved by benzoylation using copper(II) triflate and (R,R)-PhBox [2,2′-isopropylidenebis(4-phenyl-2-oxazoline)] as catalyst, which also mediated enantioselective tosylation of 2,2-bis(hydroxymethyl)alkanamides with high efficiency.

Key words - kinetic resolution - 3-hydroxyalkanamides - acylations - chiral copper complex - molecular recognition

References and Notes

<A NAME="RU10507ST-1A">1a</A> Berks AH. Tetrahedron  1996,  52:  331 

<A NAME="RU10507ST-1B">1b</A> Pàmies O. Bäckvall J.-E. Adv. Synth. Catal.  2002,  344:  947 

<A NAME="RU10507ST-1C">1c</A> Genet J.-P. Acc. Chem. Res.  2003,  36:  908 

<A NAME="RU10507ST-1D">1d</A> Mlynarski J. Eur. J. Org. Chem.  2006,  4779 

For recent literature on kinetic resolution of 3-hydroxyalkanoic acid derivatives by enzymatic methods, see:

<A NAME="RU10507ST-2A">2a</A> Xu C. Yuan C. Tetrahedron  2005,  61:  2169 

<A NAME="RU10507ST-2B">2b</A> Turcu MC. Kiljunen E. Kanerva LT. Tetrahedron: Asymmetry  2007,  18:  1682 

<A NAME="RU10507ST-3">3</A> Ishihara K. Kosugi Y. Akakura M. J. Am. Chem. Soc.  2004,  126:  12212 

<A NAME="RU10507ST-4">4</A> For a recent review of chiral bis(oxazoline) ligands, see: Desimoni G. Faita G. Jørgensen KA. Chem. Rev.  2006,  106:  3561 

<A NAME="RU10507ST-5A">5a</A> For monobenzoylation, see: Matsumura Y. Maki T. Murakami S. Onomura O. J. Am. Chem. Soc.  2003,  125:  2052 

<A NAME="RU10507ST-6B">6b</A> For monocarbamoylation, see: Matsumoto K. Mitsuda M. Ushijima N. Demizu Y. Onomura O. Matsumura Y. Tetrahedron Lett.  2006,  47:  8453 

<A NAME="RU10507ST-7C">7c</A> For monooxidation of 1,2-diols, see: Onomura O. Arimoto H. Matsumura Y. Demizu Y. Tetrahedron Lett.  2007,  48:  8668 

<A NAME="RU10507ST-8D">8d</A> For benzoylation of vic-aminoalcohols, see: Mitsuda M. Tanaka T. Tanaka T. Demizu Y. Onomura O. Matsumura Y. Tetrahedron Lett.  2006,  47:  8073 

<A NAME="RU10507ST-9E">9e</A> For a review, see: Matsumura Y. Onomura O. Demizu Y. Yuki Gosei Kagaku Kyokaishi  2007,  65:  216 

For representative literature on nonenzymatic asymmetric desymmetrization of 1,3-diols, see:

<A NAME="RU10507ST-10A">10a</A> Monocarbamoylation: Otera J. Sakamoto K. Tsukamoto T. Orita A. Tetrahedron Lett.  1998,  39:  3201 

For monobenzoylation, see:

<A NAME="RU10507ST-10B">10b</A> Oriyama T. Taguchi H. Terakado D. Sano T. Chem. Lett.  2002,  31:  26 

<A NAME="RU10507ST-10C">10c</A> Trost BM. Mino T. J. Am. Chem. Soc.  2003,  125:  2410 

<A NAME="RU10507ST-10D">10d</A> Mizuta S. Tsuzuki T. Fujimoto T. Yamamoto Y. Org. Lett.  2005,  7:  3633 

<A NAME="RU10507ST-11E">11e</A> For monoacetylation of 2-amino-1,3-diols, see: Honjo T. Nakano M. Sano S. Shiro M. Yamaguchi K. Sei Y. Nagao Y. Org. Lett.  2007,  9:  509 

<A NAME="RU10507ST-12">12</A>

Typical Procedure for Kinetic Resolution: To a solution of Cu(OTf)₂ (0.05 mmol, 18.1 mg) and (R,R)-PhBox (0.05 mmol, 16.7 mg) in EtOAc (2 mL) were added dl-6a (0.5 mmol, 89.6 mg), K₂CO₃ (0.5 mmol, 69.1 mg) and benzoyl chloride (0.25 mmol, 0.029 mL). After stirring for 2 h at r.t., to the reaction mixture H₂O (10 mL) was added. The organic portion was extracted with EtOAc (3 × 20 mL). The combined organic layer was dried over MgSO₄ and the solvent was removed in vacuo. The residue was chromatographed on SiO₂ (n-hexane-EtOAc, 3:1) to afford (S)-7a (58.1 mg, 41% yield, 85% ee) as a white solid; mp 98-99 °C; [α]_D ²³ +55.4 (c = 1.0, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 8.03 (d, J = 7.2 Hz, 1 H), 7.78 (br s, 1 H), 7.56 (t, J = 9.0 Hz, 1 H), 7.38-7.51 (m, 4 H), 7.29 (t, J = 9.0 Hz, 3 H), 7.09 (t, J = 9.0 Hz, 1 H), 5.50-5.63 (m, 1 H), 2.85 (dd, J = 6.3, 14.4 Hz, 1 H), 2.68 (dd, J = 6.3, 14.4 Hz, 1 H), 1.51 (d, J = 6.3 Hz, 3 H). Optical purity of product (S)-7a was determined by chiral HPLC: Dicel Chiralcel OD-H column (φ: 4.6 mm, l: 250 mm), n-hexane-isopropanol (10:1), wavelength: λ = 220 nm, flow rate: 1.0 mL/min, t _R = 20.0 min [(R)-7a], t _R = 22.5 min [(S)-7a].

<A NAME="RU10507ST-13">13</A>

The absolute stereoconfiguration of recovered (R)-6a was determined by comparing with the specific rotation of an authentic sample. Compound (R)-6a (74% ee): [α]_D ²² -28.6 (c = 1.1, CHCl₃) [lit. [14] (R)-6a [α]_D ²⁰ -37 (c = 1.0, CHCl₃)].

<A NAME="RU10507ST-14">14</A> Gendre PL. Offenvecher M. Bruneau C. Dixneuf PH. Tetrahedron: Asymmetry  1998,  9:  2279 

<A NAME="RU10507ST-15">15</A>

The selectivity factor s was determined using the equation s = k _{rel ( fast/slow)} = ln[(1 - C)(1 - ee_A)]/ln[(1 - C)(1 + ee_A)], where C = ee_A/(ee_A + ee_B), ee_A = ee of recovered starting material, ee_B = ee of product: Kagan H. B., Fiaud J. C.; Topics in Stereochemistry; Vol. 18. Eliel E. L.; Wiley & Sons: New York, 1988; 249-330.

<A NAME="RU10507ST-16">16</A>

Absolute stereoconfigurations of 7ap-at,av,aw shown in Table [3] were deduced on the basis of those of (S)-7a and (R)-7au.

<A NAME="RU10507ST-17">17</A>

The absolute stereoconfiguration of (R)-7au was determined by comparing with that of authentic (S)-7au, which was prepared from commercially available (S)-(-)-3-hydroxy-3-phenylpropionitrile: Dicel Chiralcel OD-H column (φ: 4.6 mm, l: 250 mm), n-hexane-isopropanol (10:1), wavelength: λ = 220 nm, flow rate: 1.0 mL/min, t _R = 36 min [(R)-7au], t _R = 42 min [(S)-7au]. (R)-7au (74% ee): [α]_D ²⁵ -13.8 (c = 1.0, CHCl₃).

<A NAME="RU10507ST-18">18</A>

Kinetic resolution of dl-6a with p-TsCl gave S-configured tosylated product with somewhat lower yield (36%) and enantioselectivity (67% ee) than those of benzoylation.

<A NAME="RU10507ST-19">19</A>

Specific rotations. 11a: [α]_D ²⁸ -16.4 (c = 1.0, CHCl₃). 11b: [α]_D ²⁸ +6.9 (c = 1.0, CHCl₃). 11c: [α]_D ²⁸ +0.6 (c = 1.0, CHCl₃). 12a: [α]_D ²⁴ +15.2 (c = 0.95, CHCl₃). 12b: [α]_D ²⁴ -21.8 (c = 1.0, CHCl₃). 12c: [α]_D ²⁶ -43.2 (c = 1.0, CHCl₃).

<A NAME="RU10507ST-20">20</A> Edin M. Martín-Matute B. Bäckvall J.-E. Tetrahedron: Asymmetry  2006,  17:  708 

<A NAME="RU10507ST-21">21</A>

Mesylation of (R)-6a followed by cyclization under basic conditions gave the corresponding optically active β-lactam with complete stereoinversion. [16]

<A NAME="RU10507ST-22">22</A> Sakaki J. Kobayashi S. Sato M. Kaneko C. Chem. Pharm. Bull.  1989,  37:  2952