Metal-Induced Reactions of O-Nitroso Aldol Products

Abstract

Lewis acid catalysts play an important role in the transformation of α-aminooxy ketones (O-nitroso aldol products). Three different reactions of O-nitroso aldol products promoted by metal ions are described.

catalysis - carbonyl complexes - transition metals - chemoselectivity - ketones

References and Notes

1a Momiyama N. Yamamoto H. Angew. Chem. Int. Ed.  2002,  41:  2986 

1b Momiyama N. Yamamoto H. Angew. Chem. Int. Ed.  2002,  41:  3313 

2a Momiyama N. Yamamoto H. J. Am. Chem. Soc.  2003,  125:  6038 

2b Momiyama N. Yamamoto H. J. Am. Chem. Soc.  2004,  126:  6498 

2c Momiyama N. Yamamoto H. J. Am. Chem. Soc.  2004,  126:  5360 

2d Momiyama N. Torii H. Saito S. Yamamoto H. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5374 

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For a representative paper, see:

3a Zhong G. Angew. Chem. Int. Ed.  2003,  42:  4247 

3b Brown SP. Brochu MP. Sinz CJ. MacMillan DWC. J. Am. Chem. Soc.  2003,  125:  10808 

3c Hayashi Y. Yamaguchi J. Hibino K. Shoji M. Tetrahedron Lett.  2003,  44:  8293 

3d Bøgevig A. Sundén H. Córdova A. Angew. Chem. Int. Ed.  2004,  43:  1109 

3e Hayashi Y. Yamaguchi J. Sumiya T. Shoji M. Angew. Chem. Int. Ed.  2004,  43:  1112 

For a review, see:

4a Merino P. Tejero T. Angew. Chem. Int. Ed.  2004,  43:  2995 

4b Janey JM. Angew. Chem. Int. Ed.  2005,  44:  4292 

4c Yamamoto H. Momiyama N. Chem. Commun.  2005,  3514 

5

α-Hydroxycyclohexanone ( 2a).
A flame-dried test tube equipped with magnetic stirring bar and a septum was charged with aminooxy ketone 1a (1.0 mmol) and dissolved in anhyd MeOH (5 mL) and THF (5 mL). CuSO₄ (0.3 mmol) was added with one portion at 0 °C. Once all of compound 1a was consumed, the reaction was quenched with pH 7.0 phosphate buffer (5 mL). The aqueous layer was then extracted four times with 5 mL of CHCl₃. The combined organic layers were then dried over Na₂SO₄, filtered and concentrated. The crude product was purified by flash chromatography on silica gel with hexanes-EtOAc as eluent. The cyclohexanone 2a was obtained as a whitish yellow liquid. TLC: R _f = 0.16 (3:1 hexane-EtOAc). ¹H NMR (400 MHz, CDCl₃): δ = 4.11 (m, 1 H, CH), 3.68 (d, 1 H, J = 3.6 Hz), 2.44-2.58 (m, 3 H, CH ₂), 2.05-2.15 (m, 1 H, CH ₂), 1.88-1.95 (m, 1 H, CH ₂), 1.40-1.70 (m, 3 H, CH ₂). ¹³C NMR (100 MHz, CDCl₃): δ = 211.4, 75.3, 39.42, 36.63, 27.50, 23.30.

6

2-(Phenylamino)cyclohex-2-enone ( 3a).
Purification by flash column chromatography with elution by hexane-EtOAc (20:1) provided a yellowish solid. TLC: R _f = 0.49 (3:1 hexane-EtOAc). ¹H NMR (400 MHz, CDCl₃): δ = 7.25 (t, 2 H, J = 8.0 Hz, ArH), 7.20 (d, 2 H, J = 8.0 Hz, ArH), 6.90 (t, 1 H, J = 8.0 Hz, ArH), 6.41 (t, 1 H, J = 4.0 Hz, CH), 6.36 (s, 1 H, NH), 2.55 (t, 2 H, CH ₂), 2.43 (dd, 2 H, CH ₂), 2.03-1.96 (m, 2 H, CH ₂). ¹³C NMR (125 MHz, CDCl₃): δ = 195.5, 141.8, 136.1, 129.1 (2 C), 120.9, 118.5 (2 C), 116.3, 37.6, 24.5, 22.8.

7

5,5-Dimethyl-2-(phenylamino)cyclohex-2-enone ( 3b). Purification by flash column chromatography with elution by hexane-EtOAc (20:1) provided a yellowish solid. TLC: R _f = 0.49 (5:1 hexane-EtOAc). ¹H NMR (400 MHz, CDCl₃): δ = 7.26 (t, 2 H, J = 8.0 Hz, ArH), 7.04 (d, 2 H, J = 8.0 Hz, ArH), 6.90 (t, 1 H, J = 8.0 Hz, ArH), 6.33
(s, 1 H, NH), 6.27 (t, 1 H, J = 4.8 Hz, CH), 2.41 (s, 2 H, CH ₂), 2.35 (d, 2 H, CH ₂), 1.11 (s, 6 H, CH ₃). ¹³C NMR (125 MHz, CDCl₃): δ = 195.6, 142.0, 135.4, 129.2 (2 C), 120.9, 118.5 (2 C), 113.7, 51.0, 38.5, 34.0, 28.2 (2 C).
4,4-Dimethyl-2-(phenylamino)cyclohex-2-enone ( 4b).
Purification by flash column chromatography with elution by hexane-EtOAc (20:1) provided a yellowish solid. TLC: R _f = 0.45 (5:1 hexane-EtOAc). ¹H NMR (400 MHz, CDCl₃): δ = 7.26 (t, 2 H, J = 8.0 Hz, ArH), 7.02 (d, 2 H, J = 8.0 Hz, ArH), 6.88 (t, 1 H, J = 8.0 Hz, ArH), 6.24 (s, 1 H, NH), 6.14 (s, 1 H, CH), 2.61 (t, 2 H, CH ₂), 1.88 (t, 2 H, CH ₂), 1.20 (s, 6 H, CH ₃). ¹³C NMR (125 MHz, CDCl₃): δ = 195.2, 141.8, 133.7, 129.2 (2 C), 126.5, 120.9, 118.5 (2 C), 35.7, 33.7, 32.4, 29.0 (2 C).

8

A flame-dried test tube equipped with a magnetic stirring bar and an aluminum cap was charged with aminooxy ketone 1b (0.2 mmol) and EuCl₃ (10 mol%), and dissolved in anhyd EtOH (1 mL). The reaction was heated at 105 °C in a microwave oven for 5 min. The reaction mixture was quenched by brine (5 mL) and the aqueous layer was extracted with CHCl₃ (2 × 10 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure after filtration. The residual crude product was purified by flash column chromatography on a silica gel using a mixture of EtOAc and hexane (1:20) as the eluant to give the product.

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