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Synlett 2010(4): 649-653  
DOI: 10.1055/s-0029-1219349
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Pauson-Khand Processes with Olefins Possessing Extended Phosphonates

Jacek L. Kędziaa, William J. Kerr*b, Allan R. McPhersonb
a Institute of Organic Chemistry, Technical University of Łódż, Zeromskiego 116, 90-924 Łódż, Poland
b Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, Glasgow, G1 1XL, Scotland, UK
Fax: +44(141)5484246; e-Mail: w.kerr@strath.ac.uk;
Further Information

Publication History

Received 23 December 2009
Publication Date:
25 January 2010 (online)

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Abstract

Olefins possessing a tethered β-functionalised phosphonate functionality have been shown to be effective cyclisation partners within intermolecular Pauson-Khand processes. The optimised protocol described facilitates intermolecular cyclisations with high levels of olefinic regiocontrol.

Key words

alkyne complexes - annulations - β-functionalised phosphonates - Pauson-Khand reaction - regioselectivity

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General Experimental Procedure A 25 mL three-necked round-bottomed flask was fitted with a condenser, flame-dried under vacuum, and allowed to cool under nitrogen. The vessel was charged with dry MeCN (7.5 mL) and the phosphonate ester (0.75 mmol). The reaction mixture was heated slowly to reflux and a solution of the desired cobalt complex (0.25 mmol) in dry MeCN (2.5 mL) was then added over 1 h via syringe pump. Following complete addition, heating was continued at reflux for 15 min. After this time, the reaction mixture was concentrated to dryness, dissolved in EtOAc, and filtered through Celite to remove cobalt residues. The filtrate was concentrated, and the crude product was purified by silica column chromatography to yield the desired regioisomeric cyclopentenones.
Sample Compound Data
Compound 6e: IR (CH2Cl2): ν = 1027, 1053, 1256, 1275, 1703, 1740 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.90 (t, 3 H, ³ J HH = 7.2 Hz), 1.28-1.37 (m, 8 H), 1.42-1.50 (m, 2 H), 2.15-2.19 (m, 2 H), 2.50-2.53 (m, 1 H), 2.67-2.80 (m, 2 H), 2.92 (d, 2 H, ² J PH = 21.6 Hz), 4.09-4.19 (m, 4 H), 4.28 (dd, 1 H, ² J HH = 11.0 Hz, ³ J HH = 6.3 Hz), 4.46 (dd, 1 H, ² J HH = 11.0 Hz, ³ J HH = 4.0 Hz), 7.30 (m, 1 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 207.6, 165.8 (d, ² J PC = 6.2 Hz), 156.5, 146.1, 64.8, 62.8 (d, ² J PC = 6.9 Hz), 62.7 (d, ² J PC = 6.7 Hz), 44.6, 34.2 (d, ¹ J PC = 134.0 Hz), 30.8, 29.7, 24.5, 22.4, 16.34, 16.28, 13.8 ppm. ³¹P NMR (162 MHz, CDCl3): δ = 19.41 ppm. HRMS (EI): m/z calcd for C16H28O6P [M++H]: 347.1618; found: 347.1623.
Compound 7e: ¹H NMR (400 MHz, CDCl3): δ = 0.92 (t, 3 H, ³ J HH = 7.3 Hz), 1.25-1.50 (m, 10 H), 2.14-2.20 (m, 3 H), 2.59 (dd, 1 H, ² J HH = 18.9 Hz, ³ J HH = 6.6 Hz), 2.99 (d, 2 H, ² J PH = 21.5 Hz), 3.14-3.23 (m, 1 H), 4.12-4.24 (m, 6 H), 7.23 (m, 1 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 208.0, 166.0 (d, ² J PC = 6.3 Hz), 156.1, 148.5, 67.3, 63.1 (d, ² J PC = 6.0 Hz), 38.38, 38.36, 34.5 (d, ¹ J PC = 133.5 Hz), 30.5, 24.7, 22.6, 16.60, 16.56, 14.0 ppm. ³¹P NMR (162 MHz, CDCl3): δ = 19.35 ppm.
The ratio of 6e/7e in the unseparated mixture was calculated from the relative integral values of the proton NMR signals at δ = 7.30 ppm (6e) and 7.23 ppm (7e). All other regioisomeric ratios were established in a similar fashion.
Isomer 7e was identified specifically as the 2,4-disubstituted cyclopentenone through the use of two-dimensional NMR experiments. Firstly, HSQC and HMBC techniques were used to determine the representative signals for the individual proton and carbon atoms. The regiochemistry of 7e was then determined by coupling correlations in the COSY spectrum and, specifically, with respect to the cyclopentenone C-4 methine proton showing direct coupling interactions with the C-3 olefinic proton, as well as the C-5 methylene unit and the O-methylene protons in the pendant side chain. The COSY spectrum for the 2,5-isomer 6e shows no coupling between the C-5 methine unit and the C-3 olefinic proton, whereas the same olefinic proton in this isomer does show a coupling interaction with the C-4 methylene unit. In all other cases (3, 4, 6a-d, 7a-d, 10, 11, 12, 13), the identity of the specific regioisomers was established more routinely through characteristic olefinic coupling patterns.