Regioselective Synthesis of Trisubstituted Cyclopentadienyl Ligands from Furans

Abstract

1,2,3- And 1,2,4-trisubstituted cyclopentadienyl manganese tricarbonyl compounds have been synthesized regioselectively from furans following a common synthetic strategy. The key steps include the transformation of furylcarbinols into hydroxycyclo­pentenones followed by the conjugate addition of Grignard reagents under chelation directed conditions. This affords hydroxycyclo­pentanones which can be dehydrated to cyclopentenones. These compounds are further elaborated into the final targets by the 1,2-addition of organolithium reagents.

Key words

cyclopentadienes - furans - metallocenes - manganese - organometallic reagents

References

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9

The addition of the organomagnesium reagent to the hydroxycyclopentenones 3 took place in a completely diastereoselective fashion giving rise to a 2,3-trans-3,4-cis stereochemistry for compounds 4. See ref. 8.

10

All compounds described throughout this work are racemic.

11

General procedure for the synthesis of cyclopentenones 6 and 7: To a solution of the corresponding hydroxycyclopentenone 2 or 3 (5 mmol) in THF (25 mL) at 0 ºC was dropwise added a solution of ArMgX (11.0 mmol, 1 M solution in THF) or MeMgI (11.0 mmol, 3 M solution in Et₂O). The mixture was heated at reflux for 2 h, cooled to r.t., and hydrolyzed with saturated NH₄Cl solution (10 mL). After extraction with EtOAc (3 × 25 mL) the combined extracts were dried on MgSO₄ and the solvent was evaporated under reduced pressure. The resulting oil was dissolved in HOAc (20 mL) and the solution was heated at reflux for 2 h. The mixture was cooled to r.t. and the solvent was evaporated under reduced pressure. The remaining oil was taken in Et₂O (20 mL) and washed with saturated NaHCO₃ (2 × 10 mL) and brine (1 × 15 mL). The solution was dried on MgSO₄ and the solvent evaporated under reduced pressure to afford an oil which was purified by chromatography (hexane-EtOAc, 8:1).

12

Compounds 10 and 11 were obtained as mixtures of double bond isomers.

13

General procedure for the synthesis of cyclopentenols 8 and 9: To a solution of cyclopentenone 6 or 7 (1 mmol) in THF (10 mL) at -78 ºC was dropwise added a solution of R³Li (1.6 mmol, 1.6 M solution of MeLi in THF, 1.8 M solution of PhLi in cyclohexane-Et₂O, or 1.0 M solution of ArLi in THF). The temperature was slowly raised to r.t. and was further stirred for 18 h. The mixture was hydrolyzed with saturated NH₄Cl (10 mL) and extracted with Et₂O (3 × 15 mL). The combined extracts were dried on MgSO₄ and the solvent was eliminated under reduced pressure to afford an oil which was purified by silica gel chromatography (hexane-EtOAc, 8:1).

14

General procedure for the synthesis of cyclopentadienes 10 and 11: To a solution of 8 or 9 (3 mmol) in Et₂O (6 mL) was added TsOH (0.6 mmol) and the solution was stirred at r.t. until disappearance of the starting material by TLC (1-6 h). The mixture was diluted with Et₂O (20 mL) and washed with saturated NaHCO₃ (2 × 10 mL) and brine (1 × 15 mL). The organic layer was dried on MgSO₄ and the solvent was eliminated under reduced pressure. The resulting oil was purified by chromatography (hexane-Et₂O, 40:1).

15

The stereochemistry of 9d was determined by NOE experiments.

16

No dealkylation of the methyl-substituted cyclopentadienes was observed under these reaction conditions. See ref. 5.

17

General procedure for the synthesis of 12 and 13: A solution of 10 or 11 (1.8 mmol) and Mn₂(CO)₁₀ (2.0 mmol) in xylene (80 mL) was heated at reflux for 24 h. The solvent was eliminated under reduced pressure and the crude reaction product was purified by chromatography (hexane-Et₂O, 10:1).