The Efficient Synthesis of Alkoxy-esters from Hydroxy Carboxylic Acids Using Dimsyllithium in Dimethylsulfoxide Followed by Alkylation with an Alkyl Halide

Philip C. Bulman Page; Yohan Chan; Harry Heaney; Matthew J. McGrath; Eduardo Moreno

doi:10.1055/s-2004-834827

LETTER

The Efficient Synthesis of Alkoxy-esters from Hydroxy Carboxylic Acids Using Dimsyllithium in Dimethylsulfoxide Followed by Alkylation with an Alkyl Halide

Philip C. Bulman Page, Yohan Chan, Harry Heaney*, Matthew J. McGrath, Eduardo Moreno
Department of Chemistry, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK
Fax: +44(1509)223926; e-Mail: h.heaney@lboro.ac.uk;

Abstract

All articles of this category

Abstract

Hydroxy acids are converted directly into the related alkyl ether-alkyl esters in high yields in a single operation by double deprotonation using dimsyllithium in dimethylsulfoxide followed by treatment with an alkyl halide.

Key words

hydroxy acids - alkoxyesters - butyllithium - dimethylsulfoxide - dimsyllithium - alkyl halide

Full Text

References

<A NAME="RD23204ST-1">1</A> Nemoto H. Takamatsu S. Yamamoto Y. J. Org. Chem. 1991, 56: 1321

<A NAME="RD23204ST-2">2</A> Kalinowski H.-O. Crass G. Seebach D. Chem. Ber. 1981, 114: 477

<A NAME="RD23204ST-3">3</A> Tsuji R. Arai S. Nishida A. Synthesis 2004, 960

For example:

<A NAME="RD23204ST-4A">4a</A> Aller E. Brown DS. Cox GG. Miller DJ. Moody CJ. J. Org. Chem. 1995, 60: 4449

<A NAME="RD23204ST-4B">4b</A> Barluenga J. Vázquez-Villa H. Ballesteros A. González JM. Org. Lett. 2002, 4: 2817

<A NAME="RD23204ST-4C">4c</A> Moreno-Dorado FJ. Guerra FM. Ortega MJ. Zubia E. Massanet GM. Tetrahedron: Asymmetry 2003, 14: 503

<A NAME="RD23204ST-5A">5a</A> Valentine D. Johnson KK. Priester W. Sun RC. Toth K. Saucy G. J. Org. Chem. 1980, 45: 3698

<A NAME="RD23204ST-5B">5b</A> Colombo L. Gennari C. Scolastico C. Guanti G. Narisano E. J. Chem. Soc., Perkin Trans. 1 1981, 1278

<A NAME="RD23204ST-5C">5c</A> Higgins SD. Thomas CB. J. Chem. Soc., Perkin Trans. 1 1982, 235

<A NAME="RD23204ST-6A">6a</A> Sakamoto T. Kondo Y. Masumoto K. Yamanaka H. J. Chem. Soc., Perkin Trans. 1 1994, 235

<A NAME="RD23204ST-6B">6b</A> Moriarty RM. Rani N. Condeiu C. Duncan MP. Prakash O. Synth. Commun. 1997, 27: 3273

<A NAME="RD23204ST-6C">6c</A> Ogura K. Watanabe J.-I. Takahashi K. Iida H. J. Org. Chem. 1982, 47: 4504

<A NAME="RD23204ST-6D">6d</A> Bonner WA. J. Am. Chem. Soc. 1951, 73: 3126

<A NAME="RD23204ST-6E">6e</A> Annunziata R. Cinquini M. Cozzi F. Gilardi A. Cardani S. Poli G. Scolastico C. J. Chem. Soc., Perkin Trans. 1 1985, 255

<A NAME="RD23204ST-6F">6f</A> Dueno EE. Chu F. Kim S.-I. Jung KW. Tetrahedron Lett. 1999, 40: 1843

<A NAME="RD23204ST-6G">6g</A> Kimura M. Kuboki A. Sigai T. Tetrahedron: Asymmetry 2002, 13: 1059

<A NAME="RD23204ST-6H">6h</A> Confalone PN. Ko SS. Tetrahedron Lett. 1984, 25: 947

<A NAME="RD23204ST-6I">6i</A> Ramig K. Englander M. Kallashi F. Livchits L. Zhou J. Tetrahedron Lett. 2002, 43: 7731

<A NAME="RD23204ST-6J">6j</A> Dueno EE. Chu F. Kim S.-I. Jung KQ. Tetrahedron Lett. 1999, 40: 1843

<A NAME="RD23204ST-7A">7a</A> Gung BW. Wolf MA. J. Org. Chem. 1993, 58: 7038

<A NAME="RD23204ST-7B">7b</A> Sutherland A. Willis CL. Tetrahedron Lett. 1997, 38: 1837

<A NAME="RD23204ST-8">8</A> Jackson WR. Jacobs HA. Jayatilake GS. Matthews BR. Watson KG. Aust. J. Chem. 1990, 43: 2045

<A NAME="RD23204ST-9A">9a</A> Heaney H. Ley SV. J. Chem. Soc., Perkin Trans. 1 1973, 499

<A NAME="RD23204ST-9B">9b</A> Heaney H. Ley SV. Org. Synth. 1974, 54: 58

<A NAME="RD23204ST-10A">10a</A> Corey EJ. Chaykovsky M. J. Am. Chem. Soc. 1962, 84: 866

<A NAME="RD23204ST-10B">10b</A> Corey EJ. Chaykovsky M. J. Am. Chem. Soc. 1965, 87: 1345

<A NAME="RD23204ST-11A">11a</A> Kriz J. Benes MJ. Peska J. Tetrahedron Lett. 1965, 2881

<A NAME="RD23204ST-11B">11b</A> Kriz J. Benes MJ. Peska J. Collect. Czech. Chem. Commun. 1967, 32: 398

<A NAME="RD23204ST-12A">12a</A> Corey EJ. Chaykovsky M. J. Am. Chem. Soc. 1964, 86: 1639

<A NAME="RD23204ST-12B">12b</A> Becker H.-D. Mikol GJ. Russell GA. J. Am. Chem. Soc. 1963, 85: 3410

<A NAME="RD23204ST-12C">12c</A> Stetter H. Hesse R. Monatsh. Chem. 1967, 98: 755

A hexane solution of n-BuLi (83 mL, 207.0 mmol, 2.5 M. 2.1 equiv) was added carefully to anhyd DMSO (150 mL) in a 500 mL round-bottomed flask. (R)-(-)-Mandelic acid (15 g, 98.7 mmol) was added and the resulting solution was stirred under nitrogen for 2 h. MeI (32.2 g, 227.0 mmol, 2.3 equiv) was then added and the reaction mixture was stirred overnight, poured into H₂O and extracted with Et₂O. The combined ethereal layers were washed with brine, dried over anhyd MgSO₄ and concentrated to afford (R)-(-)-methyl
2-methoxy-2-phenylacetate (17.8 g, 98.7 mmol, 100%). IR: ν_max = 1740 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 3.41 (s, 3 H), 3.72 (s, 3 H), 4.78 (s, 1 H), 7,34-7.45 (m, 5 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 52.7, 57.8, 82.9, 127.6, 129.1, 129.2, 136.6, 171.6 (C=O) ppm. [α]_D -113 (c 1.0, CHCl₃). HPLC on ‘Chiracel OD-H’, eluting with hexane-propan-2-ol 99:1.

IR: ν_max = 1747 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.54 (3 H, d, J = 6.9 Hz), 4.19 (1 H, q, J = 6.9 Hz), 4.53 and 4.77 (2 H, AB, J = 11.6 Hz), 5.27 and 5.28 (2 H, AB, J = 12.3 Hz), 7.39-7.45 (10, m) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 19.2 (Me), 66.5 (CH₂), 72.0 (CH₂), 74.1 (CH), 127.9 (CH), 128.1 (CH), 128.3 (CH), 128.4 (CH), 128.5 (CH), 128.7 (CH), 135.9 (C), 137.7 (C), 173.0 (C=O) ppm. HRMS (FAB): m/z calcd for C₁₇H₁₉O₃: 271.13393. Found: 271.13350 [M + 1]. [α]_D -63.3 (c 1.6, CHCl₃).

<A NAME="RD23204ST-14B">14b</A> The formation of racemic benzyl 2-benzyloxypropanoate has been reported previously by photolysis of a chromium carbene complex in the presence of carbon monoxide: Bueno AB. Moser WH. Hegedus LS. J. Org. Chem. 1998, 63: 1462

n-BuLi (3.7 mL, 9.25 mmol, 2.2 equiv) was added slowly to dry DMSO (7 mL) under nitrogen in a dry 25 mL round-bottomed flask. 2-Hydroxy-3-methylbutanoic acid (500 mg, 4.23 mmol, 1 equiv) in DMSO (7 mL) was then added. The solution was stirred during 2 h before MeI (630 µL, 10.16 mmol, 2.40 equiv) was added slowly. The reaction mixture was allowed to stir overnight and H₂O (50 mL) and Et₂O (20 mL) were then added to the mixture. The organic phase was separated, washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the methyl
2-methoxy-3-methylbutanoate as a pale yellow liquid (620 mg, 100%). IR: ν_max = 1750 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.86 (d, 3 H, J = 5.0 Hz), 0.88 (d, 3 H, J = 5.0 Hz), 1.96 (m, 1 H), 3.30 (s, 3 H), 3.44 (d, 1 H, J = 5.4 Hz), and 3.68 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 17.5 (Me), 18.5 (Me), 31.5 (CH), 51.4 (Me), 58.4 (Me), 95.9 (CH), 172.7 (C=O) ppm. HRMS (EI): m/z calcd for C₇H₁₄O₃: 146.09430. Found: 146.09460.

IR: ν_max = 1745 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.82 (3 H, d, J = 6.9 Hz), 0.84 (3 H, d, J = 6.8 Hz), 1.99 (1 H, m), 3.61 (1 H, d, J = 5.5 Hz), 4.23 and 4.55 (2 H, AB, J = 11.7 Hz), 5.04 and 5.06 (2 H, AB, J = 12.2 Hz),7.19-7.22 (10 H, m) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 17.8 (Me), 18.9 (Me), 31.7 (CH), 66.4 (CH₂), 72.5 (CH₂), 83.3 (CH), 127.8 (CH), 128.1 (CH), 128.3 (8) (CH), 128.4 (2) (CH), 128.5 (CH), 128.6 (CH), 135.9 (C), 137.8 (C), and 172.3 (C=O) ppm. HRMS (FAB): m/z calcd for C₁₇H₁₉O₃: 299.16443. Found: 299.16406 [M + 1].

IR: ν_max = 1736 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.18 (3 H, d, J = 6.2 Hz), 2.40 and 2.61 (2 H, o, AB of ABX,
J _A-B = -15.09 Hz, J _A-X = 7.52 Hz, J_B-X = 5.51 Hz), 3.95 (1 H, q × q, J = 6.2, 5.51, 7.52 Hz), 4.39 and 4.45 (2 H, AB, J = 11.6 Hz), 5.04 and 5.05 (2 H, AB, J = 12.3 Hz), and 7.23-7.26 (10 H, m) ppm. ¹³C NMR (100 MHz, CDCl₃):
δ = 19.9 (Me), 42.2 (CH₂), 66.4 (CH₂), 70.9 (CH₂), 72.2 (CH), 127.5 (CH), 127.7 (CH), 128.2 (CH), 128.2 (5) (CH), 128.3 (CH), 128.6 (CH), 136.0 (C), 138.5 (C), 171.3 (C=O) ppm. HRMS (FAB): m/z calcd for C₁₈H₂₁O₃ 285.14907. Found: 285.14941 [M + 1].