The Efficient Allylations of 2-Oxocarboxylic Acids. Synthesis of 2-Allyl Derivatives of 2-Hydroxycarboxylic Acids

Abstract

2-Oxocarboxylic acids or their sodium salts undergo indium-mediated allylation with allyl bromide cinnamyl bromide and ethyl 4- bromocrotonate to provide the corresponding 2-allyl derivatives of glycolic lactic mandelic and malic acids. In the case of reactions with cinnamyl bromide or ethyl 4-bromocrotonate high diastereoselectivity is achieved.

allylation reactions - hydroxycarboxylic acids - diastereoselective

References

1a Li CJ. Chem. Rev.  1993,  93:  2023 

1b Li CJ. Tetrahedron  1996,  52:  5643 

1c Li CJ. Chan TH. Tetrahedron  1999,  55:  11149 

1d Li CJ. Chan TH. Organic Reactions in Aqueous Media   John Wiley and Sons, Inc.; New York: 1997. 

1e Lubineau JA. Queneau Y. Synthesis  1994,  741 

2a Paquette LA. Lobben PC. J. Am. Chem. Soc.  1996,  118:  1917 

2b Chan TH. Lee MC. J. Org. Chem.  1995,  60:  4228 

2c Crao J. Houter R. Gordon DM. Whitesides GM. J. Org. Chem.  1994,  59:  3714 

2d Paquette LA. Mitzel TM. J. Am. Chem. Soc.  1996,  118:  1931 

2e Paquette LA. Mitzel TM. J. Org. Chem.  1996,  61:  8799 

2f Paquette LA. Mitzel TM. Isaac MB. Crasto CF. Schomer WW. J. Org. Chem.  1997,  62:  4293 

2g Paquette LA. Lobben PC. J. Org. Chem.  1998,  63:  5604 

2h Lobben PC. Paquette LA. J. Org. Chem.  1998,  63:  6990 

2i Kumar S. Kaur P. Chimni SS. Singh P. Synlett  2001,  1431 

3 Kumar S. Kumar V. Singh S. Chimni SS. Tetrahedron Lett.  2001,  42:  5073 

4 Kumar S. Kumar V. Chimni SS. J. Chem. Res., Synop.  2000,  314 

5a Li CJ. Lu Y. Tetrahedron Lett.  1995,  36:  2721 

5b Fujiwara N. Yamamoto Y. J. Org. Chem.  1999,  64:  4095 

6a Wada M. Honna M. Kuramoto Y. Miyoshi N. Bull. Chem. Soc. Jpn.  1997,  70:  2265 

6b Wada M. Fukuma T. Morioka M. Takahashi T. Miyoshi N. Tetrahedron Lett.  1997,  38:  8045 

7a Wang Z. Meng X. Kabalka GW. Tetrahedron Lett.  1991,  32:  4619 

7b Wang Z. Meng X. Kabalka GW. Tetrahedron Lett.  1991,  32:  5677 

8 Wang Z. Xu G. Wang D. Pierce ME. Confalone PN. Tetrahedron Lett.  2000,  41:  4523 

9

General Procedure: The 2-oxocarboxylic acid 1 (0.5 mmol), allyl bromide (0.75 mmol), indium metal (0.5 mmol) were taken in THF-H₂O (2:1) mixture and the reaction mixture was stirred at 30 °C until the indium metal dissolved. The turbid reaction mixture was treated with dilute HCl and extracted with CHCl₃. The solvent was distilled off and the residue was column chromatographed (silica gel, 60-120 mesh) to isolate the allyl addition product. In the case of reactions with sodium 2-oxocarboxylate (0.5 mmol), 2 C (1.5 mmol) and indium (1.0 mmol) the pH (4.7) of the reaction was controlled initially by addition of HOAc and during the course of reaction with aq NaOH (2%).

10

¹ H NMR spectral data for the representative cases are given here. 3e: δ 2.18 (s,1 H, OH, exchanges with D₂O), 3.86 (dd, J ₁ = 7.6 Hz, J ₂ = 4 Hz, 1 H, CH), 4.59 (d, J = 4 Hz, 1 H, CH), 5.20-5.29 (m, 2 H, =CH₂), 6.17-6.32 (m, 1 H, =CH), 7.22-7.37 (m, 5 H, ArH) (For Na salt: mp >300 °C, found C 61.4; H 5.1%. C₁₁ H₁₁O₃Na requires C 61.7; H 5.1%). 3f: mp 168 °C; δ 4.39 (s, 1 H, OH, exchanges with D₂O), 4.4 (d,
J = 9.5 Hz, 1 H, CH), 4.79-4.99 (m, 2 H, =CH₂), 5.89-6.03 (m, 1 H, =CH), 7.19-7.41 (m, 8 H, ArH), 7.72-7.73 (m, 2 H, ArH) (Found C 76.3; H 5.99%. C₁₇H₁₆O₃ requires C 76.1; H 5.97%). 3g : δ 1.31 (t, J = 7 Hz, 3 H, CH₃), 2.09 (s, 1 H, OH, exchanges with D₂O), 3.62 (dd, J ₁ = 8.4 Hz, J ₂ = 3.6 Hz,
1 H, CH), 4.20 (s, 1 H, OH, exchanges with D₂O), 4.22 (q,
J = 7 Hz, 2 H, OCH₂) 4.47 (d, J = 3.6 Hz, 1 H, CH), 5.26-5.38 (m, 2 H, =CH₂), 5.77-6.07 (m, 1 H, =CH) (For Na salt: mp >300 °C; found C 45.4, H 4.9. C₈H₁₁O₅Na requires C 45.7; H, 5.2%). 3 h: mp 97-98 °C; δ 1.29 (t, J = 7.2 Hz,
3 H,CH₃), 2.20 (s, 1 H, OH, exchanges with D₂O), 4.14 (d,
J = 8.2 Hz, 1 H, CH), 4.22 (q, J = 7.2 Hz, 2 H, OCH₂), 5.02-5.17 (m, 2 H, =CH₂), 5.56-5.68 (m, 1 H, =CH), 7.29-7.42 (m, 8 H, ArH), 7.58-7.63 (m, 2 H, ArH). (Found C 63.3;
H 6.0%. C₁₄ H₁₆O₅ requires C 63.3; H 6.06%).

11

Similar increase in both rate of reaction and diastereoselectivity of allylation at pH 4.0 and slowed allylation at pH 7.0 was reported earlier (ref. [2d] ).