· (MW 338.28)
(reagent used as a nucleophile with a wide array of carbonyl bearing electrophiles)
Physical Data: air and water sensitive dark red crystals; mp 110-113 °C (decomposes).
Solubility: soluble in THF, diethyl ether, benzene, toluene.
Handling, Storage, and Precautions: this compound should be handled under inert atmosphere (nitrogen or argon), especially in solution. In the solid state, brief exposure to air does not seem to significantly deteriorate the quality of the compound, but storage of the solid should also be under inert atmosphere. Scrupulously dry solvents are required, as this compound reacts readily with water.
Preparative Methods: this compound should be prepared using the method described.1 The trimethylphosphine complex is more crystalline and easier to isolate. The titanium reagent is best used within 1 month of preparation.
General Addition of Electrophiles to the Dienyl Ligand
(h5-2,4-Cyclopentadien-1-yl)[(1,2,3,4,5-h)-6,6-dimethyl-2,4-cy-clohexadien-1-yl](triethylphosphine)titanium C19H31TiP (from here on out referred to as the titanium complex) is an excellent nucleophile with a variety of carbonyl-containing compounds. Depending on the reaction conditions, one of three possible products can result from the reaction of the dienyl portion of the 6,6-dimethylcyclohexadienyl (dmCh) ligand (1). These products are a net 1,4-addition of two equiv (1), a net 1,4-addition of two equiv with oxidation at the 5-position (2), or a single addition of one equiv to the 1-position (3). Careful manipulation of the reaction conditions and carbonyl substrate can significantly favor one product over the other two. Details of specific electrophiles are discussed in the following sections.
Addition of Ketones
Following the literature procedure for the coupling reaction with ketones,1 products from incorporation of two equiv of ketone have been isolated (2). These 1,4-addition reactions are unusual for analogous titanium pentadienyl complexes,2 and this sort of addition appears to be dependent upon this specific metal-ligand complex. Interestingly, the addition reaction is stereospecific, and the syn-addition is the only observed product (1).
Some of the substrates form a triol product as the major product where the third hydroxyl group in the 5-position is anti to the new bonds at the 1- and 4-positions on the former dmCh ligand. It was found that exposure of the reaction mixture to a source of oxygen (air) produced the triol as the major product. The precise source of this third hydroxyl group is not known.1,3
Addition of Acid Chlorides
Products of 1,4-addition can also be seen for an acid chloride (3).3 The product is isolated in a much lower yield (ca. 25%), and the reaction was not as clean. Notably, this is the first, and only, reported reaction of dienyl ligands with an acid chloride.
Addition of Aldehydes
Addition products have also been seen with aldehydes (4).1 In these cases, the aldehydes also add in a syn manner to the dmCh ligand. Acyclic pentadienyl systems are not known to participate in reactions with aldehydes.1 In these cases, three possible products may be isolated: one equiv of aldehyde may be incorporated at the 1-position giving a diene product (R = Ph, i-Pr, t-Bu); two equiv may be incorporated at the 1- and 4-positions (R = i-Pr, t-Bu); and two equiv may be incorporated and the 5-position may be oxidized (R = I-Pr, t-Bu). For the coupling reaction of benzaldehyde, the only product isolated was the monoaddition product as a 5:1 mixture of inseparable diastereomers. In addition, no more than one equiv of electrophile was successfully added even in the presence of five equiv of aldehyde (2).
However, the addition reactions of pivaldehyde and isobutyraldehyde proved much more interesting. In these cases, the 1,4-addition product was isolated as a single diastereomer, where four new stereocenters were formed. Exposure of the reaction mixture to air gave the triol, also as a single diastereomer, from the addition of pivaldehyde.4 (Stereochemical determinations were made via the formation of the acetonides and comparison of 13C values of the acetonide and through X-ray crystallographic analysis.) Therefore, the titanium complex produced five new stereocenters in a single operation.
Mixed Addition Reactions
Addition of two different carbonyl-containing electrophiles to the titanium complex was also explored (3). Even in the presence of one equiv of initial ketone or aldehyde (other than benzaldehyde) followed by an excess of another carbonyl compound, the major product isolated is always incorporation of two equiv of the initial ketone or aldehyde as in eqs 2 and 4. For this reason, benzaldehyde was chosen as the first carbonyl reactant as this aldehyde gave exclusively monoaddition products. Carbonyl compounds that have been used as the second electrophile included a ketone and an acid chloride (5).
Aldehydes were not successfully incorporated into these mixed coupling reactions. For these reactions, even under forcing conditions (excess aldehyde, reflux) only the monoaddition product of benzaldehyde was observed. While yields were modest, successful incorporation of two different carbonyl compounds was observed.
- 1. Wilson, A. M.; West, F. G.; Arif, A. M.; Ernst, R. D., J. Am. Chem. Soc. 1995, 117, 8490.
- 2. (a) Ernst, R. D., Comments Inorg. Chem. 1999, 3, 285. (b) Waldman, T. E.; Wilson, A. M.; Rheingold, A. L.; Melendez, E.; Ernst, R. D., Organometallics 1992, 11, 3201. (c) Wilson, A. M.; Waldman, T. E.; Rheingold, A. L.; Ernst, R. D., J. Am. Chem. Soc. 1992, 114, 6252. (d) Melendez, E.; Arif, A. M.; Ernst, R. D.; Ziegler, M. L., Angew. Chem., Int. Ed. Engl. 1988, 27, 1099.
- 3. Wilson, A. M., PhD Dissertation, University of Utah, 1994.
- 4. (a) Rychnovsky, S. D.; Yang, G.; Powers, J. P., J. Org. Chem. 1993, 58, 5251. (b) Evans, D. A.; Rieger, D. L.; Gage, J. R., Tetrahedron Lett. 1990, 31, 7099. (c) Rychnovsky, S. D.; Skalitzky, D. J., Tetrahedron Lett. 1990, 31, 945.
Anne M. Wilson
Butler University, Indianapolis, USA
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