Cyclisation of Unsaturated N-Chloroamines under Acidic Conditions: A Polar Reaction via Chloronium Ions

Abstract

Unsaturated N-chloroamines cyclise under acidic conditions without addition of a starter for a radical reaction. Therefore it can be concluded that, under the conditions published to date in the literature, the reaction at least partially proceeds via a polar reaction mechanism rather than via free radicals.

cyclisation - heterocycles - addition reactions - aminations

References

For reviews see:

1a Minisci F. Synthesis  1973,  1 

1b Stella L. Angew. Chem., Int. Ed. Engl.  1983,  22:  337 

1c Stella L. In Radicals in Organic Synthesis   Vol. 2:  Wiley-VCH; Weinheim: 2001.  p.407 

2a Hemmerling M. Sjöholm Å. Somfai P. Tetrahedron: Asymmetry  1999,  10:  4091 

2b Sjöholm Å. Hemmerling M. Pradeille N. Somfai P. J. Chem. Soc., Perkin Trans. 1  2001,  891 

3a Stella L. Raynier B. Surzur JM. Tetrahedron  1981,  37:  2843 

3b Borch RF. Evans AJ. Wade JJ. J. Am. Chem. Soc.  1975,  97:  6282 

3c Roush WR. J. Am. Chem. Soc.  1980,  102:  1390 

4a Newcomb M. Deeb TM. Marquardt DJ. Tetrahedron  1990,  46:  2317 

4b Horner JH. Martinez FN. Musa OM. Newcomb M. Shahin HE. J. Am. Chem. Soc.  1995,  117:  11124 

5a Göttlich R. Noack M. Tetrahedron Lett.  2001,  7771 

5b Noack M. Göttlich R. Eur. J. Org. Chem.  2002,  3171 

6

We have performed the reaction in deuterated acetic acid and detected the intermediate by NMR.

This rearrangement is known:

7a Fusaon RC. Zirkle CL. J. Am. Chem. Soc.  1948,  70:  2760 

7b Hammer CF. Heller SR. Craig JH. Tetrahedron  1972,  28:  239 

In the first reports by Minisci a polar mechanism was always considered as an alternative reaction pathway:

8a Minisci F. Galli R. Cecere M. Chim. Ind. (Milan, Italy)  1966,  48:  347 

8b Neale RS. J. Org. Chem.  1967,  32:  3263 

8c Surzur J.-M. Stella L. Tordo P. Bull. Soc. Chim. Fr.  1970,  115 

8d For other experiments using Lewis acids see: Heumann A. Furstoss R. Waegell B. Tetrahedron Lett.  1972,  993 

9

Reaction conditions: To a solution of 2 mmol chloroamine in 5 mL CH₂Cl₂ 4 mmol BF₃·ΟEt₂ was added at -78 °C and the reaction stirred at this temperature for 1 h. Then 10 mL aq KOH (10%) was added and the mixture was allowed to warm to r.t. The organic phase was separated and the aquous layer washed twice with 10 mL CH₂Cl₂ each. The combined organic layers were dried over Na₂SO₄, the solvent removed in vacuo and the product obtained from the residue by flash-chromatography. NMR-data of 2a (d ₆-benzene): ¹H NMR (300 MHz): δ = 0.90 (s, 3 H), 0.91 (t, 3 H, J = 7.1 Hz), 1.06 (s, 3 H), 1.18-1.45 (m, 4 H), 1.50 (dd, 1 H, J = 12.6 and 6.3 Hz), 1.72 (dd, 1 H, J = 12.6 and 8.7 Hz), 1.91 (d, 1 H, J = 9.0 Hz), 2.08 (m, 1 H), 2.51 (m, 1 H), 2.65 (m, 1 H), 2.73 (d, 1 H, J = 8.4 Hz), 3.21 (dd, 1 H, J = 10.5 and 8.4 Hz), 3.44 (dd, 1 H, J = 10.5 and 3.6 Hz). ¹³C NMR (75 MHz): δ = 14.1, 20.7, 28.1, 29.5, 31.5, 36.3, 45.0, 47.9, 54.7, 66.4, 68.1. Exact mass spectrometry: C₁₁H₂₂NCl, calcd: 203.14358; found: 203.14426.

10

In the proposed radical-type cyclisations of chloroamines by Somfai, borontrifluoride etherate was found to be the superior Lewis acid too (see ref. 3).

11 For an overview see: Jung MF. Synlett  1999,  843