Enantiopure α-Silyl-Substituted α-Hydroxyacetic Acids Using O-H Insertion Methodology and Boron-Based Asymmetric Reductions

Abstract

Two routes to optically active α-silyl-substituted α-hydroxyacetic acids are described. As a key step, the first utilizes O-H insertion reactions of (R)-and (S)-phenylethanol into benzyl 2-silyl-2-diazoacetates in the presence of [Rh₂(OAc)₄]. Alternatively, asymmetric reductions of benzyl 2-silyl-2-oxoacetates using (R)-Alpine-Borane^® afford the corresponding α-hydroxy esters with up to 91% ee.

hydroxy acids - O-H insertion - dirhodium(II) acetate - diazo compounds - asymmetric borane reduction

References

<A NAME="RG43604ST-1">1</A>

New address: Beiersdorf AG, Unnastr. 48, 20245 Hamburg, Germany.

<A NAME="RG43604ST-2">2</A>

New address: ProBioGen AG, Goethestr. 50-54, 13086 Berlin, Germany.

<A NAME="RG43604ST-3">3</A> Coppola GM. Schuster HF. α-Hydroxy Acids in Enantioselective Synthesis   Wiley-VCH; Weinheim: 1997. 

<A NAME="RG43604ST-4A">4a</A> Pandey G. Das P. Reddy PY. Eur. J. Org. Chem.  2000,  657 

<A NAME="RG43604ST-4B">4b</A> Yu H. Ballard CE. Wang B. Tetrahedron Lett.  2001,  42:  1835 

<A NAME="RG43604ST-4C">4c</A> Yu H. Ballard CE. Boyle PD. Wang B. Tetrahedron  2002,  58:  7663 

<A NAME="RG43604ST-4D">4d</A> Loupy A. Monteux DA. Tetrahedron  2002,  58:  1541 

<A NAME="RG43604ST-4E">4e</A> Bauer T. Gajewiak J. Synthesis  2004,  20 

<A NAME="RG43604ST-5">5</A> Adam W. Fell RT. Stegmann VR. Saha-Möller CR. J. Am. Chem. Soc.  1998,  120:  708 

<A NAME="RG43604ST-6A">6a</A> Adam W. Lazarus M. Boss B. Saha-Möller CR. Humpf H.-U. Schreier P. J. Org. Chem.  1997,  62:  7841 

<A NAME="RG43604ST-6B">6b</A> Adam W. Boland W. Hartmann-Schreier J. Humpf H.-U. Lazarus M. Saffert A. Saha-Möller CR. Schreier P. J. Am. Chem. Soc.  1998,  120:  11044 

<A NAME="RG43604ST-6C">6c</A> Groger H. Adv. Synth. Catal.  2001,  343:  547 

<A NAME="RG43604ST-6D">6d</A> Osprian I. Fechter MH. Griengl H. J. Mol. Catal. B: Enzym.  2003,  24-25:  89 

<A NAME="RG43604ST-7A">7a</A> Huerta FF. Bäckvall J.-E. Org. Lett.  2001,  3:  1209 

<A NAME="RG43604ST-7B">7b</A> Pamies O. Bäckvall J.-E. Adv. Synth. Catal.  2002,  344:  947 

<A NAME="RG43604ST-8">8</A> Yakura T. Tanaka T. Ikeda M. Uenishi J. Chem. Pharm. Bull.  2003,  51:  471 

<A NAME="RG43604ST-9">9</A> Bolm C. Kasyan A. Heider P. Saladin S. Drauz K. Günther K. Wagner C. Org. Lett.  2002,  4:  2265 

<A NAME="RG43604ST-10A">10a</A> Nagai K. Sunazuka T. Omura S. Tetrahedron Lett.  2004,  45:  2507 

<A NAME="RG43604ST-10B">10b</A> Qu Z. Shi W. Wang J. J. Org. Chem.  2004,  69:  217 

<A NAME="RG43604ST-10C">10c</A> Review: Miller DJ. Moody CJ. Tetrahedron  1995,  51:  10811 

<A NAME="RG43604ST-11">11</A>

General Procedure for O-H Insertion.
To a stirred and degassed solution of 4 (581 mg, 2 mmol) and an excess of the corresponding alcohol (5-10 mmol) in dry toluene (15 mL) at r.t. was added [Rh_{2 (}OAc)₄] (18 mg, 0.04 mmol, 2 mol%). The reaction mixture was heated to 50 °C and was left stirring at this temperature for 16 h. After the reaction mixture was cooled to ambient temperature, the solvent was removed under reduced pressure, and the crude product was purified by flash column chromatography on silica gel (petroleum ether- tert-butyl methyl ether as eluents, various gradients). All products were obtained as clear oils upon evaporation of the solvents and dried in high vacuum.
Characteristic NMR data for benzyl 2-[(1S)-1-phenylethyl-oxy]-2-triethylsilylacetate [(+)-6a] stemming from the reaction between 4 and (S)-(-)-5a: Major diastereomer: [α]_D +14.2 (c 1.2, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.57 (q, J = 8.2 Hz, 6 H), 0.86 (t, J = 8.2 Hz, 9 H), 1.35 (d, J = 6.4 Hz, 3 H), 4.04 (s, 1 H), 4.35 (q, J = 6.4 Hz, 1 H), 4.89 (d, J = 12.1 Hz, 1 H), 4.95 (d, J = 12.4 Hz, 1 H), 7.14-7.31 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 2.1, 7.2, 21.3, 65.9, 70.8, 79.6, 126.6, 127.3, 128.1, 128.5, 128.5, 136.0, 143.5, 173.7. Minor diastereomer: [α]_D -133.6 (c 0.5, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 0.49 (q, J = 7.7 Hz, 6 H), 0.78 (t, J = 8.2 Hz, 9 H), 1.37 (d, J = 6.3 Hz, 3 H), 3.70 (s, 1 H), 4.35 (q, J = 6.3 Hz, 1 H), 5.08 (s, 2 H), 7.12-7.30 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 0.9, 1.1, 5.7, 6.0, 6.1, 23.0, 64.7, 68.7, 78.0, 125.3, 125.8, 126.0, 126.5, 127.0, 127.1, 127.2, 134.8, 141.5, 172.6.

Reviews:

<A NAME="RG43604ST-12A">12a</A> Cho BT. Aldrichimica Acta  2002,  35:  3 

<A NAME="RG43604ST-12B">12b</A> Cho BT. Chun YS. In Organoboranes for Synthesis   Ramachandran PV. Brown HC. ACS Symposium Series 783, American Chemical Society; Washington DC: 2001.  p.122 

<A NAME="RG43604ST-13A">13a</A> Midland MM. Chem. Rev.  1989,  89:  1553 

<A NAME="RG43604ST-13B">13b</A> Ramachandran PV. Pitre S. Brown HC. J. Org. Chem.  2002,  67:  5315 

<A NAME="RG43604ST-14A">14a</A> Brown HC. Cho BT. Park WS. J. Org. Chem.  1988,  53:  1231 

<A NAME="RG43604ST-14B">14b</A> Cho BT. Chun YS. Tetrahedron: Asymmetry  1992,  3:  73 

<A NAME="RG43604ST-15A">15a</A> Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1986 

<A NAME="RG43604ST-15B">15b</A> Deloux L. Srebnik M. Chem. Rev.  1993,  93:  763 

<A NAME="RG43604ST-15C">15c</A> Singh VK. Synthesis  1992,  605 

<A NAME="RG43604ST-15D">15d</A> Wallbaum S. Martens J. Tetrahedron: Asymmetry  1992,  3:  1475 

<A NAME="RG43604ST-15E">15e</A> Schwink L. Knochel P. Chem.-Eur. J.  1998,  4:  950 

<A NAME="RG43604ST-16">16</A>

Procedure for the Reduction of 1b Using ( R )-Alpine-Borane. To a stirring and degassed solution of (R)-Alpine-Borane^® (7) in THF (1.1 mL, 0.5 M soln) at -20 °C under an argon atmosphere was added benzyl 2-triethylsilyl-2-oxoacetate (1b, 75 µL, 0.27 mmol) using a microliter syringe. The reaction mixture was left standing for 96 h at -20 °C, after which a phosphate buffer (pH = 7, 0.1 mL) and 30% H₂O₂ solution (67 µL) were simultaneously added. The reaction mixture was left stirring in an ice bath for 2.5 h. Flash column chromatography on silica gel (15:1 hexane-EtOAc) afforded benzyl 2-triethylsilyl-2-hydroxyacetate (2b) as a colorless oil in 71% yield (54 mg) and 91% ee (for the details of the ee-determination see footnote b in Table [2] ).

<A NAME="RG43604ST-17">17</A>

X- ray crystallographic study of (R)-3c: The compound (C₈H₁₈O₃Si; M _r = 190.31) crystallizes in orthorhombic space group P2₁2₁2₁ (Nr. 19) with cell dimensions a = 6.5280 (6), b = 6.9443 (8), c = 24.237 (4)Å. A cell volume of V = 1098.7 (2) ų and Z = 4 result in a calculated density of δ _cal = 1.150 g cm^-3. 2911 Reflections have been collected in the ω/2Θ mode at T = 150 K on an Enraf Nonius CAD4 diffractometer employing CuK_α-radiation (λ = 1.54179 Å). Data collection covered the range -8£h£8,
-8£k£8, and -30£l£30 (Friedel pairs) up to Θ_max = 72.7°. No absorption correction (m = 1.679 mm^-1). The structure has been solved by direct methods as implemented in the Xtal3.7 suite of crystallographic routines [18] where GENSIN has been used to generate the structure-invariant relationships and GENTAN for the general tangent phasing procedure. 2054 Observed reflections [I>2σ(I)] have been included in the final full-matrix least-squares refinement on F involving 182 parameters and converging at R(R _w ) = 0.042 (0.050, w = 1/σ² (F), S = 2.256, and a residual electron density of -0.47/0.59 e Å^-3. The absolute configuration has been determined using Flack’s method. X_abs = 0.023 (70) [19] for the structure shown in Figure [2] . The hydrogen positions could be located and have been refined isotropically. The crystal structure of (R)-3c has been deposited as supplementary publication no. CCDC 255777 at the Cambridge Crystallographic Data Centre. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone]; e-mail: [e-mail], or http//www.ccdc.cam.ac.uk].

<A NAME="RG43604ST-18">18</A> Xtal3.7 System   Hall SR. du Boulay DJ. Olthof-Hazekamp R. University of Western Australia; Australia: 2000. 

<A NAME="RG43604ST-19">19</A> Flack HD. Acta Crystallogr., Sect. A  1983,  39:  876