Tris(acetylacetonato)cobalt-Diethylaluminum Chloride-NORPHOS


[21679-46-9]  · C15H21CoO6  · Tris(acetylacetonato)cobalt-Diethylaluminum Chloride-NORPHOS  · (MW 356.29) (Et2AlCl)

[96-10-6]  · C4H10AlCl  · Tris(acetylacetonato)cobalt-Diethylaluminum Chloride-NORPHOS  · (MW 120.57) ((+)-NORPHOS)

[71042-54-1]  · C31H28P2  · Tris(acetylacetonato)cobalt-Diethylaluminum Chloride-NORPHOS  · (MW 462.53)

(catalyst for the formation of optically active deltacyclene derivatives by homo Diels-Alder reaction of norbornadiene with substituted acetylenes1,2)

Physical Data: see Diethylaluminum Chloride and (+)-trans-(2S,3S)-Bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene (NORPHOS).

Solubility: sol THF, benzene, toluene.

Preparative Methods: synthesized in situ from the three components, using a 1.5 excess of the chelate phosphine; the components are commercially available or can be easily prepared.

Handling, Storage, and Precautions: the in situ catalyst should be used in an atmosphere of dry nitrogen or argon, in a fume hood. The catalyst components can be stored indefinitely. They are air stable except Et2AlCl, which should be kept under exclusion of air.

The Homo Diels-Alder Reaction of Norbornadiene with Acetylenes.

[2 + 2 + 2] Cycloadditions of dienes such as norbornadiene with the double bonds in 1,4-position are called homo Diels-Alder reactions. Using an in situ catalyst (consisting of Co(acac)3-Et2AlCl-bis(diphenylphosphino)ethane) the products obtained with monosubstituted acetylenes, such as phenyl, i-propyl-, n-butyl-, t-butyl-, and trimethylsilylacetylene, are 4-substituted deltacyclenes.1,2 In the formation of the polycyclic deltacyclene skeleton, six new stereo centers are generated in one step. Thus enantiocontrol by using optically active phosphine ligands as cocatalysts allows the synthesis of optically active cycloadducts,3-5 as shown for the reaction of norbornadiene with phenylacetylene to give 4-phenyldeltacyclene (eq 1).

Preparation of the in situ Catalyst and Catalytic Reaction.

(This is a typical procedure for norbornadiene and phenylacetylene or 1-hexyne). Tris(acetylacetonato)cobalt (7.1 mg, 2.0 × 10-2 mmol) and (+)-NORPHOS (13.8 mg, 3.0 × 10-2 mmol) are dissolved in 1 ml of THF under dry nitrogen, using standard Schlenk techniques. Norbornadiene (1.0 mL, 10.0 mmol) and 10 mmol of phenylacetylene or 1-hexyne are added. The reaction is started by addition of 5 mL of a 1M solution of diethylaluminum chloride in hexane. The reaction mixture is kept at 35 °C for 4 h. Then 5 mL of isopropanol are added and the volatile components are removed in vacuum. The oily residue is distilled at 80 °C in high vacuum in a Kugelrohr apparatus. Chemical yield >99%; enantiomeric excess 98.4-99.6% for (+)-4-phenyldeltacyclene and 97.6-98.0% for (+)-4-n-butyldeltacyclene.

Product Analysis.

The distilled product is dissolved in 2 mL of dry methylene chloride and an internal standard is added (naphthalene for 4-phenyldeltacyclene, biphenyl for 4-n-butyldeltacyclene). The chemical yield and the enantiomeric excess of the product can be determined by GLC using a 40 m column of perpentylated b-cyclodextrin. 4-Phenyldeltacyclene: column temperature 104 °C, retention time (-)-isomer 124.7 min, (+)-isomer 128.2 min; 4-n-butyldeltacyclene: column temperature 65 °C, retention time (-)-isomer 78.3 min, (+)-isomer 80.8 min.

Variation of the Optically Active Phosphine Ligand (Cocatalyst) and the Solvent.5

In the synthesis of 4-phenyldeltacyclene, (+)-NORPHOS as the optically active ligand and THF as the solvent gave the best results, as indicated in the typical procedure. Used in benzene, the NORPHOS-containing catalyst also gives extremely high enantioselectivities but low chemical yields. With PROPHOS as the ligand, quantitative conversion in THF is only achieved after long reaction times. The enantiomeric excess in this case was ca. 80%. CHIRAPHOS and BDPP as cocatalysts result in slow conversions of the starting materials, BDPP giving high optical yields. In the case of DIOP in benzene, only low chemical and optical yields are obtained. In THF, DIOP-containing catalysts are inactive, as are BINAP-containing catalysts in benzene/THF.

For 4-n-butyldeltacyclene, no other cocatalyst gives the quantitative yield and 98-99% enantiomeric excess observed in the NORPHOS-containing system. The PROPHOS system gives 80% enantiomeric excess.

Variation of the Procatalyst (Metal Component) and the Acetylenic Substrate.

The in situ catalysts Co(acac)3-Et2AlCl-phosphine have proven to be well-suited for the synthesis of 4-aryl- and 4-alkyl-substituted deltacyclenes. The catalysts tolerate remote oxygen functionalities in the acetylenic substrate.4 However, they could not be used with functionalized acetylenes such as propargylic acid derivatives.

Recently, new procatalysts have been reported. They contain different cobalt sources and reducing agents. The procatalyst CoI2-Zn has proven valuable in the preparative homo Diels-Alder reaction.6 It has been shown that monodentate and bidentate ligands of the aminophosphine and phosphite type, e.g. ValNOP and ProliNOP, give high optical yields in the synthesis of 4-phenyldeltacyclene and 4-n-butyldeltacyclene.7 With these new procatalysts, an extension of the homo Diels-Alder reaction to functionalized acetylenes is possible. High chemical and optical yields are obtained in the reaction of norbornadiene with substrates such as propargylic and homopropargylic ethers and esters.8

1. Lyons, J. E.; Myers, H. K.; Schneider, A. CC 1978, 636.
2. Lautens, M.; Crudden, C. M. OM 1989, 8, 2733.
3. Brunner, H.; Muschiol, M.; Prester, F. AG 1990, 102, 680; AG(E) 1990, 29, 652.
4. Lautens, M.; Lautens, J. C.; Smith, A. C. JACS 1990, 112, 5627.
5. Brunner, H.; Prester, F. JOM 1991, 414, 401.
6. Duan, I.-F.; Cheng, C.-H.; Shaw, J.-S.; Cheng, S.-S.; Liou, K. F. CC 1991, 1347.
7. Pardigon, O.; Buono, G. TA 1993, 4, 1977.
8. Buono, G.; personal communication.

Henri Brunner

Universität Regensburg, Germany

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