Regioselective Pauson-Khand Processes with Allylphosphonates as the Olefinic Partners

Abstract

The ability of allylphosphonates to act as the olefinic partner within the Pauson-Khand reaction has been investigated. It has been found that these substrates not only react efficiently within the developed reaction manifold but also deliver good to excellent levels of olefinic regiocontrol.

alkyne complexes - allylphosphonates - annulations - Pauson-Khand reaction - regioselectivity

References

1a Khand IU. Knox GR. Pauson PL. Watts WE. J. Chem. Soc., Chem. Commun.  1971,  36 

1b Khand IU. Knox GR. Pauson PL. Watts WE. Foreman MI. J. Chem. Soc., Perkin Trans. 1  1973,  977 

2a Pauson PL. Tetrahedron  1985,  41:  5855 

2b Schore NE. In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.1037 

2c Schore NE. Org. React.  1991,  40:  1 

2d Schore NE. In Comprehensive Organometallic Chemistry II   Vol. 12:  Abel EW. Stone FGA. Wilkinson G. Elsevier; New York: 1995.  p.703 

2e Geis O. Schmalz H.-G. Angew. Chem. Int. Ed.  1998,  37:  911 

2f Chung YK. Coord. Chem. Rev.  1999,  188:  297 

2g Brummond KM. Kent JL. Tetrahedron  2000,  56:  3263 

2h Chin CS. Won G. Chong D. Kim M. Lee H. Acc. Chem. Res.  2002,  35:  218 

2i Gibson SE. Mainolfi N. Angew. Chem. Int. Ed.  2005,  44:  3022 

3 Magnus P. Principle LM. Tetrahedron Lett.  1985,  26:  4581 

4a Krafft ME. J. Am. Chem. Soc.  1988,  110:  968 

4b Krafft ME. Juliano CA. Scott IL. Wright C. McEachin MD. J. Am. Chem. Soc.  1991,  113:  1693 

4c Krafft ME. Juliano CA. J. Org. Chem.  1992,  57:  5106 

4d See also: Krafft ME. Tetrahedron Lett.  1988,  29:  999 

5a Waszkuć W. Janecki T. Org. Biomol. Chem.  2003,  1:  2966 

5b Janecki T. Wąsek T. Tetrahedron  2004,  60:  1049 

5c Baszczyk E. Krawczyk H. Janecki T. Synlett  2004,  2685 

6a Shambayati S. Crowe WE. Schreiber SL. Tetrahedron Lett.  1990,  31:  5289 

6b Jeong N. Chung YK. Lee BY. Lee SH. Yoo S.-E. Synlett  1991,  204 

6c Gordon AR. Johnstone C. Kerr WJ. Synlett  1995,  1083 

6d Donkervoort JG. Gordon AR. Johnstone C. Kerr WJ. Lange U. Tetrahedron  1996,  52:  7391 

7 Sugihara T. Yamada M. Ban H. Yamaguchi M. Kaneko C. Angew. Chem., Int. Ed. Engl.  1997,  36:  2801 

8a Sugihara T. Yamada M. Yamaguchi M. Nishizawa M. Synlett  1999,  771 

See also:

8b Kerr WJ. Lindsay DM. McLaughlin M. Pauson PL. Chem. Commun.  2000,  1467 

8c Brown JA. Kerr WJ. Irvine S. Pearson CM. Org. Biomol. Chem.  2005,  3:  2396 

9 Chung YK. Lee BY. Jeong N. Hudecek M. Pauson PL. Organometallics  1993,  12:  220 

10

General Experimental Procedure.
A 250-mL three-necked round-bottomed flask was flame dried under vacuum and allowed to cool under nitrogen prior to being fitted with a reflux condenser. The entire system was then purged three times with nitrogen gas. The vessel was charged with dry CH₂Cl₂ (5.0 mL), dry MeCN (5.0 mL), and diethyl allylphosphonate (1.0 mmol). The reaction mixture was heated slowly to reflux at which time a solution of the desired cobalt complex (0.5 mmol) in dry CH₂Cl₂ (10.0 mL) was added over 8 h via syringe pump. Following complete addition, heating was continued at reflux for 10 h. After this time, the mixture was concentrated to dryness, dissolved in EtOAc, and filtered through Celite to remove cobalt residues. The filtrate was concentrated and the resultant oil distilled under vacuum to remove any excess alkene starting material. The residue was then purified by silica column to yield the desired regioisomeric cyclopentenones. The ratio of these regioisomers was determined by ¹H NMR. Sample data:
Diethyl (2-oxo-3-phenylcyclopent-3-enyl)methylphos-phonate (3): IR (CH₂Cl₂): ν = 1027, 1054, 1133, 1247, 1447, 1494, 1598, 1704 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.34 (t, 3 H, ^³ J _HH = 7.1 Hz), 1.36 (t, 3 H, ^³ J _HH = 7.1 Hz), 1.73 (ddd, 1 H, ^² J _PH = 16.6 Hz, ^² J _HH = 15.5 Hz, ^³ J _HH = 11.7 Hz), 2.54 (ddd, 1 H, ^² J _PH = 18.2 Hz, ^² J _HH = 15.5 Hz, ^³ J _HH = 2.9 Hz), 2.71 (dt, 1 H, ^² J _HH = 19.8 Hz, ^³ J _HH = 2.8 Hz), 2.77-2.87 (m, 1 H), 3.08 (ddd, 1 H, ^² J _HH = 19.8 Hz, ^³ J _HH = 6.8 Hz, ^³ J _HH = 3.2 Hz), 4.08-4.23 (m, 4 H), 7.32-7.42 (m, 3 H), 7.68-7.73 (m, 2 H), 7.83 (dd, 1 H, ^³ J _HH = 3.2 Hz, ^³ J _HH = 2.8 Hz) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 207.4, 157.7, 142.3, 131.4, 128.8, 128.7, 127.2, 62.0, 41.5, 34.0, 27.3, 16.7 ppm. ³¹P NMR (162 MHz, CDCl₃): δ = 30.87 ppm. HRMS (EI): m/z calcd for C₁₆H₂₂O₄P [M⁺ + H]: 309.1250; found: 309.1247. Anal. Calcd for C₁₆H₂₁O₄P: C, 62.33; H, 6.87; P, 10.05. Found: C, 62.21; H, 6.82; P, 9.90.
Diethyl (4-oxo-3-phenylcyclopent-2-enyl)methylphos-phonate (4): ¹H NMR (400 MHz, CDCl₃): δ = 1.35 (t, 3 H, ^³ J _HH = 7.1 Hz), 1.37 (t, 3 H, ^³ J _HH = 7.1 Hz), 1.97 (ddd, 1 H, ^² J _PH = 17.8 Hz, ^² J _HH = 15.2 Hz, ^³ J _HH = 8.3 Hz), 2.05 (ddd, 1 H, ^² J _PH = 18.1 Hz, ^² J _HH = 15.2 Hz, ^³ J _HH = 6.6 Hz), 2.44 (dd, 1 H, ^² J _HH = 19.0 Hz, ^³ J _HH = 2.5 Hz), 2.92 (dd, 1 H, ^² J _HH = 19.0 Hz, ^³ J _HH = 6.7 Hz), 3.26-3.38 (m, 1 H), 4.08-4.19 (m, 4 H) 7.32-7.45 (m, 3 H), 7.68-7.73 (m, 2 H), 7.82 (d, 1 H, ^³ J _HH = 2.6 Hz) ppm. ³¹P NMR (162 MHz, CDCl₃): δ = 29.14 ppm.
Isomer 3 was identified as the major product by its characteristic ¹H NMR resonances at δ = 2.71, 3.08, and 7.83 ppm. The splitting and coupling constants associated with these signals is indicative of structure 3. This can be compared with the corresponding ¹H NMR resonances for compound 4 at δ = 2.44, 2.92, and 7.82 ppm. The ratio of 3:4 in the unseparated mixture was established from the relative integral values of the signals at δ = 2.77-2.87 ppm (in 3) and δ = 3.26-3.38 ppm (in 4). All other regioisomeric ratios were established in a similar fashion.